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Biomedical subjects

H Okada

Publications and source records attributed to H Okada.

At least 271 records · Page 15Linked to original sources

Alterations in binding site density of dopamine transporter in the striatum, orbitofrontal cortex, and amygdala in early Parkinson's disease: compartment analysis for beta-CFT binding with positron emission tomography.

We investigated changes in the kinetics in the binding of the dopamine transporter probe 2-beta-carbomethoxy-3beta-(4-[11C]fluorophenyl)tropane (beta-CFT) in living brain by compartmental analysis, using positron emission tomography in unmedicated patients with Parkinson's disease (PD) (Hoehn and Yahr stages I-II). With dynamic positron emission tomographic data from 90-minute acquisitions and metabolite-corrected arterial input functions, binding potentials (k3/k4) were calculated by using estimated rate constants (K1 - k4). In this analysis, the magnitude of the distribution volume (K1/k2) measured in the cerebellum, in which specific binding is negligible, was used as a constrained value for fitting in binding regions. Statistics showed that k3/k4 values in the striatum, the orbitofrontal cortex, and the amygdala were significantly lower in PD patients than in normal controls, whereas there were no differences in K1/k2 ratios and structural volumes between the groups. Correlation analysis showed that the putaminal and orbitofrontal binding levels were correlated positively with motor and mentation scores, respectively, of the Unified Parkinson's Disease Rating Scale. These results indicated that not only the striatal but also the orbitofrontal and amygdalar presynaptic dopaminergic functions were altered in early PD. The reductions in these mesocortical/mesolimbic functions might contribute to the mental and behavioral impairment observed in PD.

Aged↗

[A case of true carcinosarcoma in bladder diverticulum].

We report a case of carcinosarcoma arising from a bladder diverticulum. A 71-year-old male was referred to our hospital for macroscopic hematuria. Two diverticula were identified in the left wall of the urinary bladder, one of which showed a broad-based tumor. The bladder tumor was resected using a transuretheral approach and the tumor was histologically diagnosed as leiomyosarcoma. The patient underwent partial resection of the bladder including the two diverticula and the tumor. Pathological examination revealed that the resected specimen was composed of three elements, transitional cell carcinoma (G3), squamous cell carcinoma, and leiomyosarcoma. Thus, the patient was diagnosed with carcinosarcoma. He died 5 months after surgery to remove the panperitonitis carcinomatosa. This case is the 38th reported case of bladder carcinosarcoma in Japan.

Aged↗

[Low flow anesthesia at a fresh gas flow of 10 ml.kg-1.min-1 for hours using time-cycled ventilator].

Low flow anesthesia (LFA) at a fresh gas flow (FGF) level of 10 ml.kg-1.min-1 with oxygen flow set at 0.5 ml.kg-1.min-1: 0.5 ml.kg-1.min-1 nitrous oxide and 3% isoflurane was performed using time-cycled ventilator on 10 patients of ASA class I or II, with age of 55 +/- 13 (mean +/- SD) years and body weight of 55 +/- 10 kg for 5 h. Excessive anesthetic gases from the anesthesia gas monitor were led to an expiratory breathing tube. After rapid induction and tracheal intubation, denitrogenation was performed for about 5 min using a 100% oxygen flow of 6 l.min-1 before LFA. The inspired/expired oxygen concentration decreased gradually from 96 +/- 2%/90 +/- 2% at beginning of LFA to 42 +/- 3%/37 +/- 4% at 5 h. The operation was started after 29 +/- 10 min of beginning of LFA. The nitrous oxide concentration reached 37 +/- 4%/35 +/- 4% at the beginning of operation and further increased to 55 +/- 3%/53 +/- 3% at 5 h. The isoflurane concentration reached 1.0 +/- 0.1%/0.8 +/- 0.1% at the beginning of operation and further increased to 1.2 +/- 0.1%/1.0 +/- 0.1% at 5 h. The anesthetic potency was 1.2 +/- 0.1 MAC/1.0 +/- 0.2 MAC at the beginning of operation. The isoflurane vaporizer setting was changed only once in two cases from 3% to 2% exceeding 1.5% in inspired concentration. There was no need to change the flow of oxygen and nitrous oxide for 5 hrs. No SpO2 lower than 95% was observed during this study. This method is a clinically safe, easily applicable anesthesia method and used the smallest FGF reported in LFA without occurrence of low FIO2.

Adult↗

[Inflammatory pseudotumor of the lung].

The patient was a 76-year-old man whose chief complaint was a dry cough. His chest X-ray film revealed a large hazy shadow with unclear margin in the left upper lobe. Bronchiolitis obliterans organizing pneumonia was initially diagnosed because transbronchial lung biopsy (TBLB) specimens showed organizing pneumonia with no evidence of malignancy. However, because the hazy shadow increased gradually in size despite steroid therapy. TBLBs were performed several more times to confirm the diagnosis. The last TBLB specimen showed proliferation of fibroblasts and mononuclear cells, with marked infiltration mainly of plasma cells 12 months after the initiation of steroid therapy. Because we were unable to obtain a histological diagnosis by bronchofiberscopy, a left upper lobectomy was preformed and the lesion resected. Histology disclosed inflammatory pseudotumor of a lymphoplasmacytic type with organizing pneumonia. The results of an immuno-histochemical examination confirmed that the proliferating plasma cells were polyclonal. These findings suggest that inflammatory pseudotumors should be taken into account by differential diagnoses of cases of organizing pneumonia that are resistant to steroid therapy.

Aged↗

[Laparoscopic resection of retroperitoneal tumors: report of two cases].

Here we report two rare cases of retroperitoneal tumors which were found incidentally and resected laparoscopically. Case 1; A 43-year-old woman presented with general fatigue and revealed liver dysfunction. Although the initial diagnosis with computed tomography (CT) was left non-functioning adrenal tumor, it was proven as a retroperitoneal tumor adjacent to the left adrenal gland by laparoscopic examination. The tumor was resected laparoscopically and diagnosed histopathologically as a solitary retroperitoneal neurofibroma. Case 2; A 68-year-old man was being followed for a renal stone and a perirenal tumor was found by CT. It was resected laparoscopically and diagnosed as a mature retroperitoneal teratoma by histopathological examination. We conclude that laparoscopic resection is useful for the retroperitoneal tumors as well as for adrenal tumors.

Adult↗

[Apneic anesthesia for microsurgery of the larynx under propofol anesthesia].

Apneic anesthesia with intermittent ventilation (AAIV) under inhalational anesthesia has been reported to improve visualization of the larynx with lack of vocal cord motion in laryngeal microsurgery. In this study, we evaluated AAIV using total intravenous anesthesia with propofol and fentanyl instead of inhalational anesthesia in 11 patients undergoing microsurgery of the larynx, and examined the effects of AAIV on respiration and circulation. Anesthesia was maintained with infusion of propofol 4-10 mg.kg-1.h-1 and intermittent administration of fentanyl and vecuronium intravenously. The lungs were ventilated with 100% oxygen, and the endotracheal tube was removed during the apneic period. AAIV provided the otorhinolaryngologist sufficient room in which to operate and an immobile field without complications in any of the patients. The number of periods of apnea (mean +/- SD) was 3.3 +/- 1.3, and the duration of apnea was 292 +/- 23 seconds. Neither blood pressure nor heart rate changed during the apneic periods. Arterial oxygen saturation measured using pulse oxymetry (Spo2) changed in none of the patients except an obese patient whose Spo2 declined to 90%. End-tidal carbon dioxide level increased for 14.9 mmHg immediately after apneic periods. Propofol vielded stable and adequate levels of anesthesia during apneic periods. We conclude that AAIV using constant monitoring of Spo2 is a useful and safe technique, and that propofol is a suitable anesthetic agent for AAIV.

Anesthesia, Intravenous↗

Incidence of gingival hyperplasia caused by calcium antagonists in continuous ambulatory peritoneal dialysis patients.

Calcium antagonists are widely used for the treatment of cardiovascular diseases in patients receiving dialysis therapy. The incidence of gingival hyperplasia has been reported as 10%-20% in patients treated with calcium antagonists in the general population. However, precise reports examining the incidence or pathogenesis of gingival hyperplasia in continuous ambulatory peritoneal dialysis (CAPD) patients are lacking. We recruited 54 CAPD patients. Three patients treated with long-acting nifedipine and one patient treated with felodipine were reported by a periodontist to have gingival hyperplasia. No patients were taking amlodipine and other calcium antagonists. After discontinuation of calcium antagonists, gingival hyperplasia disappeared within 1 month. Based on these results, we suggest that it is important to examine whether the gingiva is overgrown in CAPD patients taking calcium antagonists.

Adult↗

Evidence that gender difference affects peritoneal dialysis capacity in continuous ambulatory peritoneal dialysis patients.

The progression of renal disease is reported to be more rapid in male patients than in premenopausal females. However, few studies compare the difference in dialysis therapy between males and females. We compared the efficacy of peritoneal dialysis capacity, using measurements of retention volume and pelvic cavity by helical section of computed tomography (CT) in 6 male and 6 female patients. The patients did not differ significantly in age (males: 54 +/- 3 years; female: 56 +/- 4 years). Males were heavier than females (p < 0.05). Retention volume in the visceral cavity was significantly larger in males (1787 +/- 43 mL) than in females (1580 +/- 59 mL) (p < 0.05). Peritoneal dialysis capacity was evaluated by peritoneal equilibration test (PET). Although no significant differences were observed in the PET data, when the PET results at 4 hours were divided by body weight in kilograms, a significant difference between males and females was seen (p < 0.05). There was a mild, but not significant, correlation between the volume of the pelvis as measured by helical CT and the PET data per kilogram body weight (p = 0.07). These results suggest that gender differences in peritoneal dialysis capacity relate partially to the difference in pelvic cavity volume.

Female↗

Long-term experience with orthotopic reconstruction of the lower urinary tract in women.

PURPOSE: We investigated the long-term outcome of orthotopic neobladders in women. MATERIALS AND METHODS: At our institutions 8 women have undergone lower urinary tract reconstruction with an orthotopic neobladder and have been followed for more than 4 years. After urethral sparing cystectomy the neobladder was constructed and connected to the native urethra. Late complications were analyzed, and voiding function was evaluated by a pressure flow micturition study and bead-chain cystourethrography. RESULTS: No late complications related to the surgery were noted. Of the 8 patients 7 were completely dry day and night. Four patients with ileal neobladder required clean intermittent catheterization, and hypercontinence might have been caused by downward migration of the neobladder and reduced neobladder pressure at voiding. No recurrence in the native urethra was noted, and all patients were satisfied postoperatively. CONCLUSIONS: These results of orthotopic neobladder in women are encouraging. Overall patient satisfaction was excellent. An international collaborative study is necessary to achieve the number of patients required to determine the ideal orthotopic neobladder for women.

Adult↗

The inositol phosphatase SHIP inhibits Akt/PKB activation in B cells.

The serine-threonine kinase Akt/PKB is activated downstream of phosphatidylinositol 3-kinase in response to several growth factor stimuli and has been implicated in the promotion of cell survival. Although both phosphatidylinositol 3,4,5-trisphosphate (PIP3) and phosphatidylinositol 3,4-bisphosphate (PI 3,4-P2) have been implicated in the regulation of Akt activity in vitro, the relative roles of these two phospholipids in vivo are not well understood. Co-ligation of the B cell receptor (BCR) and the inhibitory FcgammaRIIB1 on B cells results in the recruitment of the 5'-inositol phosphatase SHIP to the signaling complex. Since SHIP is known to cleave PIP3 to generate PI 3,4-P2 both in vivo and in vitro, and Akt activity has been reported to be regulated by either PIP3 or PI 3,4-P2, we hypothesized that recruitment of SHIP through FcgammaRIIB1 co-cross-linking to the BCR in B cells might regulate Akt activity. The nature of this regulation, positive or negative, might also reveal the relative contribution of PIP3 and PI 3,4-P2 to Akt activation in vivo. Here we report that Akt is activated by stimulation through the BCR in a phosphatidylinositol 3-kinase-dependent manner and that this activation is inhibited by co-cross-linking of the BCR to FcgammaRIIB1. Using mutants of FcgammaRIIB1 and SHIP-deficient B cells, we demonstrate that inhibition of Akt activity is mediated by the immune cell tyrosine-based inhibitory motif within FcgammaRIIB1 as well as SHIP. The SHIP-dependent inhibition of Akt activation also suggests that PIP3 plays a greater role in Akt activation than PI 3,4-P2 in vivo.

Animals↗

Attenuation of regional differentiation of sympathetic nerve activity during sleep in humans.

The purpose of the present study was to clarify how the regional differentiation of sympathetic nerve activity (SNA) is modified during natural sleep in humans. In humans, muscle and skin sympathetic nerve activities (MSNA, SSNA) have been reported to discharge independently according to a regional differentiation of SNA during wakefulness. However, in natural sleep, MSNA and SSNA have been documented to synchronize during sleep stage 2 (Rechtschaffen and Kales). In the present study, we measured MSNA and SSNA simultaneously using a double recording technique of microneurography in eight healthy volunteers during natural sleep, and analyzed how MSNA and SSNA can be synchronized. We found that the synchronicity of MSNA and SSNA was accelerated in correlation with the deepening of the non-rapid eye movement (nonREM) sleep stages. We also documented that the burst properties of MSNA different from those of SSNA in wakefulness become similar to those of SSNA in the sleep stage, and MSNA synchronizes with SSNA. The synchronicity of MSNA and SSNA is presumably caused by a reduced effect of central inhibitory baroreflex pathways on MSNA during nonREM sleep. The present findings suggest that the regional differentiation of sympathetic nerve activity is attenuated with the deepening of nonREM sleep stages.

Adult↗

Role of the inositol phosphatase SHIP in B cell receptor-induced Ca2+ oscillatory response.

Src homology-2 domain-containing inositol polyphosphate 5'-phosphatase (SHIP) is a recently identified protein that has been implicated as an important signaling molecule. Although SHIP has been shown to participate in the FcgammaRIIB-mediated inhibitory signal, the functional role of SHIP in activation responses by immunoreceptor tyrosine-based activation motif-bearing receptors such as B cell receptor (BCR) remains unclear. Indeed, it has been proposed that SHIP serves as a linking molecule for the regulation of the extracellular signal-regulated kinase pathway in BCR signaling, because SHIP associates with Shc. We now report that SHIP-deficient DT40 B cells display enhanced Ca2+ mobilization in response to BCR ligation, whereas extracellular signal-regulated kinase activation is unaffected. This Ca2+ enhancement is due to a sustained intracellular Ca2+ increase or to long-lasting Ca2+ oscillations by loss of SHIP, as revealed by single-cell Ca2+ imaging analysis. These results demonstrate the importance of SHIP in B cell activation by the modulation of Ca2+ mobilization.

Animals↗

Intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats and humans.

In this study, we investigated the intestinal absorption of luteolin and luteolin 7-O-beta-glucoside in rats by HPLC. The absorption analysis using rat everted small intestine demonstrated that luteolin was converted to glucuronides during passing through the intestinal mucosa and that luteolin 7-O-beta-glucoside was absorbed after hydrolysis to luteolin. Free luteolin, its conjugates and methylated conjugates were present in rat plasma after dosing. This suggests that some luteolin can escape the intestinal conjugation and the hepatic sulfation/methylation. LC/MS analysis showed that the main conjugate which circulates in the blood was a monoglucuronide of the unchanged aglycone. Luteolin in propyleneglycol was absorbed more rapidly than that in 0.5% carboxymethyl cellulose. The plasma concentration of luteolin and its conjugates reached the highest level 15 min and 30 min after dosing with luteolin in propyleneglycol, respectively. HPLC analysis also allowed us to demonstrate the presence of free luteolin and its monoglucuronide in human serum after ingestion of luteolin.

Animals↗

AML1(-/-) embryos do not express certain hematopoiesis-related gene transcripts including those of the PU.1 gene.

The AML1 and PEBP2beta/CBFbeta genes encode the DNA-binding and non-binding subunits, respectively, of the heterodimeric transcription factor, PEBP2/CBF. Targeting each gene results in an almost identical phenotype, namely the complete lack of definitive hematopoiesis in the fetal liver on embryonic day 11.5 (E11.5). We examined and compared the expression levels of various hematopoiesis-related genes in wild type embryos and in embryos mutated for AML1 or PEBP2beta/CBFbeta. The RNAs were prepared from the yolk sacs of E9.5 embryos, from the aorta-gonad- mesonephros regions of E11.5 embryos and from the livers of E11.5 embryos and RT-PCR was performed to detect various gene transcripts. Transcripts were detected for most of the hematopoiesis-related genes that encode transcription factors, cytokines and cytokine receptors, even in tissues from homozygously targeted embryos. On the other hand, PU.1 transcripts were never detected in any tissue of AML1(-/-) or PEBP2beta/CBFbeta(-/-) embryos. In addition, transcripts for the Vav, flk-2/flt-3, M-CSF receptor, G-CSF receptor and c-Myb genes were not detected in certain tissues of the (-/-) embryos. The results suggest that the expression of a particular set of hematopoiesis-related genes is closely correlated with the PEBP2/CBF function.

Animals↗

Bone marrow-derived dendritic cells pulsed with a tumor-specific peptide elicit effective anti-tumor immunity against intracranial neoplasms.

Although the central nervous system (CNS) is often regarded as an immunologically privileged site, it is well established that specific CNS immunoreactivity can be generated through peripheral vaccination with CNS antigens. Dendritic cells (DC) are potent antigen presenting cells of hematopoietic origin that have emerged as a promising tool for cancer immunotherapy capable of evoking significant anti-tumor immunity when pulsed with tumor-associated peptides. To explore a role for DC-based immunization strategies for the treatment of CNS tumors, we developed a brain tumor model using the C3 sarcoma cell line which expresses the tumor-specific, major histocompatibility complex (MHC) class I-restricted peptide epitope E7(49-57). Syngeneic C57Bl/6 mice receiving intravenous (i.v.) injections of bone marrow-derived DCs pulsed with E7 peptide were effectively protected against a subsequent intracerebral challenge with C3 tumor cells. More importantly, this systemic immunization strategy was effective in a therapy model as 67% of animals (10 of 15) with established (day 7) intracerebral C3 tumors treated with 3 weekly injections of E7 peptide-pulsed DCs achieved a long-term survival (>90 days) while no control animals survived beyond day 41. In vivo depletion of CD8+ cells, but not CD4+ or asialo-GM1+ cells, abrogated the efficacy of E7 peptide-pulsed DC therapy of established tumors, indicating a pivotal role of specific CD8+ T-cell responses in mediating the anti-tumor effect. Our findings support the hypothesis that effective CNS anti-tumor immunoreactivity can be generated with DC-based tumor vaccines.

Animals↗

Involvement of guanosine triphosphatases and phospholipase C-gamma2 in extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 mitogen-activated protein kinase activation by the B cell antigen receptor.

Mitogen-activated protein (MAP) kinase family members, including extracellular signal-regulated kinase (ERK), c-Jun NH2-terminal kinase ( JNK), and p38 MAP kinase, have been implicated in coupling the B cell antigen receptor (BCR) to transcriptional responses. However, the mechanisms that lead to the activation of these MAP kinase family members have been poorly elucidated. Here we demonstrate that the BCR-induced ERK activation is reduced by loss of Grb2 or expression of a dominant-negative form of Ras, RasN17, whereas this response is not affected by loss of Shc. The inhibition of the ERK response was also observed in phospholipase C (PLC)-gamma2-deficient DT40 B cells, and expression of RasN17 in the PLC-gamma2-deficient cells completely abrogated the ERK activation. The PLC-gamma2 dependency of ERK activation was most likely due to protein kinase C (PKC) activation rather than calcium mobilization, since loss of inositol 1,4,5-trisphosphate receptors did not affect ERK activation. Similar to cooperation of Ras with PKC activation in ERK response, both PLC-gamma2-dependent signal and GTPase are required for BCR-induced JNK and p38 responses. JNK response is dependent on Rac1 and calcium mobilization, whereas p38 response requires Rac1 and PKC activation.

Adaptor Proteins, Signal Transducing↗

Mechanosensitive cation channels mediate afferent arteriolar myogenic constriction in the isolated rat kidney.

1. In order to assess ionic mechanisms mediating renal afferent arteriolar myogenic constriction, experiments were performed using isolated perfused hydronephrotic rat kidneys. 2. Increasing pressure progressively constricted the afferent arteriole (-0.26 +/- 0.02% mmHg-1, n = 21, r = 0.97). Gadolinium (10 microM), a mechanosensitive cation channel blocker, abolished this myogenic constriction. However, high potassium media (30 mM) constricted the afferent arteriole in the presence of gadolinium. 3. Lowering extracellular sodium concentration gradually attenuated afferent arteriolar myogenic constriction. In the perfusate containing 50 mM sodium, the myogenic response was arrested. 4. Afferent arteriolar myogenic constriction was prevented in calcium-free perfusate or by the L-type calcium channel blocker diltiazem (10 microM). 5. Our present findings provide evidence that increasing pressure gates mechanosensitive cation channels on the afferent arteriole, thereby eliciting membrane depolarization and activating voltage-dependent calcium channels.

Animals↗