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Biomedical subjects

S Noda

Publications and source records attributed to S Noda.

At least 55 records · Page 3Linked to original sources

Improvement of solubility and oral bioavailability of rutin by complexation with 2-hydroxypropyl-beta-cyclodextrin.

The object of this study was to enhance the solubility, dissolution rate, and oral bioavailability of rutin by complexation with 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD). The interaction of rutin with cyclodextrins (CyDs) was evaluated by the solubility, and ultraviolet (UV) and circular dichroism (CD) spectrophotometries. The chemical and enzymatic stability of rutin was examined in an alkaline buffer solution and in rat small intestinal homogenates, respectively. Dissolution rates of rutin and its CyD complexes were measured by the dispersed amount method. In vivo absorption studies of rutin after oral administration via conventional tablet containing rutin alone or its beta-CyD complexes was performed on beagle dogs. The stability constants calculated from the phase solubility method increased in the order of HP-gamma-CyD < G2-beta-CyD < beta-CyD < HP-beta-CyD. Spectroscopic studies also revealed that HP-beta-CyD and beta-CyD formed a relatively more stable inclusion complex with rutin. The dissolution rates of rutin increased by the complexation with CyDs in the order of rutin alone < HP-beta-CyD < or = beta-CyD. HP-beta-CyD inhibited the hydrolysis of rutin in the alkaline buffer solution and the small intestinal homogenates of rats, suggesting that HP-beta-CyD may stabilize rutin in a gastrointestinal tract after oral administration. When the tablet containing rutin or its beta-CyD complexes was administered to beagle dogs, the plasma levels of homovanillic acid (HVA) (a major stable metabolite of rutin) after oral administration of HP-beta-CyD complex were much higher than in either that of rutin alone or in its beta-CyD complex. The in vivo absorption study suggests that HP-beta-CyD increased the oral bioavailability of rutin from the gastrointestinal tracts of beagle dogs because of the increase in solubility, faster dissolution rate, and gastrointestinal stability. HP-beta-CyD has a significant advantage with respect to providing high aqueous solubility while maintaining a lack of toxicity in oral pharmaceutical preparations of rutin.

2-Hydroxypropyl-beta-cyclodextrin↗

Relationship between MRI findings and prognosis for patients with general paresis.

MRI was performed in 7 patients with general paresis before or at a very early stage of treatment. A large dose of antibiotics, mainly penicillin, was given to all patients, and the effects of treatment, the patients' outcome, and MRI findings were investigated. Three of the 7 patients had MRI findings of atrophy of the medial temporal lobe including the hippocampus. In the medial temporal lobe atrophy group, a personality change or general dementia remained even after the treatment was completed, and outcome in social functioning was poor. Medial temporal lobe atrophy may be a poor prognostic sign in general paresis.

Adult↗

The myocilin (MYOC) gene expression in the human trabecular meshwork.

PURPOSE: We previously reported a novel cytoskeletal protein with a myosin-like domain which is localized in the ciliary rootlet and basal body of connecting cilium of photoreceptor and hence we named it 'myocilin'. It was soon realized that myocilin is identical to a protein called TIGR (trabecular meshwork inducible glucocorticoid response protein) which was found to be responsible for the pathogenesis of juvenile open angle glaucoma. In this study, we employed in situ RNA hybridization to examine the myocilin (MYOC)/ TIGR gene expression in the trabecular meshworks of glaucomatous and nonglaucomatous eyes. METHODS: The glaucomatous specimens were obtained by trabeculectomy from the patients with primary open angle glaucoma (POAG), chronic angle closure glaucoma (CACG) and steroid glaucoma, respectively, and the nonglaucomatous specimens were obtained from a victim of traffic accident at autopsy and from a patient with maxillary sinus carcinoma at enucleation for the operation. The in situ RNA hybridization was carried out with digoxigenin-labeled sense and antisense RNA probes. RESULTS: In all cases, hybridization signals were detected primarily in the trabecular meshwork cells and secondarily in the fibroblast-like cells of corneoscleral wall. CONCLUSIONS: Myocilin gene is expressed clearly in the trabecular meshwork cells of both glaucomatous and nonglaucomatous eyes.

Aged↗

Transurethral holmium laser resection of the prostate.

PURPOSE: We evaluated the efficacy of the holmium:YAG laser for transurethral endoscopic prostatectomy for benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: We treated 103 patients with BPH with holmium:YAG laser resection of the prostate. A high power holmium laser generating a maximum of 60 or 81 W. was used in a pulsed mode, applying energy directly to prostatic tissue via a forward firing 550 micron. fiber transurethrally under direct vision. Treatment outcome was evaluated by the International Prostate Symptom Score, quality of life score, maximum flow rate and post-void residual urine volume. We also compared holmium laser surgery and transurethral resection of the prostate for operative factors, such as surgical duration, bleeding volume and catheterization time. RESULTS: Average symptom score, quality of life score, peak flow rate and post-void residual significantly improved at 1 week, 1 month and 3 months postoperatively, with improvement maintained up to 36 months postoperatively in the holmium:YAG group. Intraoperative bleeding volume was significantly lower and catheterization time was significantly shorter for holmium:YAG than for transurethral prostatic resection. Use of the holmium laser caused no complications. CONCLUSIONS: Because of its effectiveness and safety holmium:YAG resection is a viable potential surgical alternative for symptomatic BPH. The holmium:YAG laser has been verified to be useful for many purposes in urology.

Aged↗

Overexpression of wild-type Akt1 promoted insulin-stimulated p70S6 kinase (p70S6K) activity and affected GSK3 beta regulation, but did not promote insulin-stimulated GLUT4 translocation or glucose transport in L6 myotubes.

We have developed a simple, direct and sensitive method to detect GLUT4 on the cell surface. Using this system, we found that PI3-kinase plays a key role in the signaling pathway of insulin-stimulated GLUT4 translocation. One of the down stream effectors of PI3-kinase is serine-threonine kinase Akt (protein kinase B, RAK-PK), but the involvement of Akt in insulin-stimulated GLUT4 translocation is controversial. To investigate whether Akt1 regulates insulin-stimulated GLUT4 translocation and glucose uptake in L6 myotubes, we established L6 myotubes stably expressing c-myc epitope-tagged GLUT4 (GLUT4myc) and mouse wild type (WT) Akt1. We found that overexpression of WT Akt1 promoted insulin-stimulated p70S6 kinase (p70S6K) activity and increased the basal activity of GSK3 beta, but did not promote insulin-stimulated GLUT4 translocation or glucose uptake. These data supported the result that Akt is not a main signaling molecule to transmit the signal of insulin-stimulated GLUT4 translocation or glucose uptake from insulin-activated PI3-kinase.

Amino Acid Sequence↗

Expression of the SART3 tumor rejection antigen in renal cell carcinoma.

PURPOSE: We recently reported that SART3 tumor rejection antigen is recognized by HLA class I restricted cytotoxic T lymphocytes from patients with esophageal cancer. We now investigate the expression of SART3 antigen in renal cell carcinoma to identify an appropriate molecule that may be used in specific immunotherapy of renal cell carcinoma. MATERIALS AND METHODS: Renal cell carcinoma and nontumorous kidney tissues were obtained at surgery. A section of each sample was minced with scissors and stored at -80C until use. SART3 antigen expression was examined in uncultured renal cell carcinoma and nontumorous kidney tissues. We also evaluated the ability of derived peptides to include cytotoxic T lymphocytes in peripheral blood mononuclear cells from patients with renal cell carcinoma. RESULTS: The SART3 antigen was detected in all renal cell carcinoma cell lines, primary cultures of renal cell carcinoma and nontumorous kidney tissues, and in the cytosol of 57% and 15% of renal cell carcinoma and nontumorous kidney tissues, respectively. HLA-A2402 restricted and tumor specific cytotoxic T lymphocytes (KE4) used in cloning of the SART3 gene were significantly cytotoxic to cells from renal cell carcinoma cell lines and primary cultures of renal cell carcinoma tissue but they did not lyse normal cells, including those from primary cultures of nontumorous kidney tissue. The SART3 peptides derived from positions 109-118 and 315-323 induced HLA-A24 restricted cytotoxic T lymphocytes to renal cell carcinoma cells from peripheral blood mononuclear cells of patients with renal cell carcinoma. CONCLUSIONS: The SART3 antigen and derived peptides may be applied to the specific immunotherapy of HLA-A24+ renal cell carcinoma.

Adult↗

[Neurosarcoidosis with girdle sensation and polyradiculoneuropathy masquerading as Guillain-Barré syndrome].

We herein report two patients with neurosarcoidosis presenting girdle sensation in the trunk and polyradiculoneuritis. The first patient, a 53-year-old woman, manifested subacute progressive paresthesia in all four limbs and below the Th 3 level with girdle sensation from the thorax to lower abdomen and mild weakness in the left upper limb and the bilateral lower limbs. The patient was diagnosed to have sarcoidosis based on a biopsy of the scalenus anticus lymph nodes. The second patient, a 63-year-old woman, showed an acute onset of weakness and paresthesia in all four limbs and girdle sensation from the Th 5 to Th 8 level. On examination, she demonstrated diminished tendon reflexes in all four limbs, mild to severe weakness in all four limbs, paresthesia in all four limbs and below the Th 5 level. Although Guillain-Barré syndrome was initially suspected in this patient, the presence of girdle sensation led us to examine the possibility of neurosarcoidosis. Her examination demonstrated an abnormal accumulation of gallium in the bilateral hilar lymph nodes and mediastinum on scintigraphy, an elevated CD 4/CD 8 ratio in the bronchoalveolar lavage fluid, a negative tuberculin reaction, and elevated serum lysozyme level. These findings thus fulfilled the clinical criteria for sarcoidosis. None of the two patients showed any abnormalities in the thoracic cord MRI. In the first patient F wave was not evoked in either upper or lower limbs, while in the second patient temporal dispersion on M wave was observed in the right median and both ulnar nerves. We therefore consider the girdle sensation to have not been caused by myelopathy but instead by polyradiculopathy. When sarcoid peripheral neuropathy masquerades as Guillain-Barré syndrome, then the presence of girdle sensation may help diagnosis of neurosarcoidosis.

Diagnosis, Differential↗

[Repeated deterioration of tuberculous meningitis due to a reduction in the corticosteroid dosage during chemotherapy].

A 17-year-old man with a high fever, confusion and neck stiffness was diagnosed to have tuberculous meningitis, and was immediately placed on prednisolone (40 mg/day) as well as standard antituberculosis drugs (isoniazid, rifampicin and pyrazinamide). The clinical symptoms improved rapidly and the number of cerebrospinal fluid(CSF) cells decreased from 1837/mm3 on admission to 76/mm3 on the 7th day. Thereafter the dosage of prednisolone was gradually reduced. As a result, however increased nuchal rigidity, papilloedema and an increase in the number of CSF cells of 934/mm3 were all observed on the 35th day. Prednisolone thus again administered at the original dosage and the patient quickly showed a clinical improvement. CSF cells decreased to 271/mm3 on the 70th day. When prednisolone was again tapered down, increased nuchal rigidity, abducent nerve palsy and papilloedema appeared again with a marked increase in the number of CSF cells of 1309/mm3 on the 91th day. Therefore, we continued to treat the patient with prednisolone, in addition to the standard antituberculosis treatment, at a dose of 80 mg/day and tapered off very slowly over six months. This treatment resulted in a marked recovery with no recurrence. In this case, prednisolone was indispensable for treating tuberculous meningitis in combination with appropriate antituberculosis drugs, though the role of corticosteroids has remained controversial over the years. This case might be an example of paradoxical progression in tuberculous meningitis.

Adolescent↗

Human and mouse ISLR (immunoglobulin superfamily containing leucine-rich repeat) genes: genomic structure and tissue expression.

We have previously reported a transcript of the novel gene for human immunoglobulin superfamily containing leucine-rich repeat (ISLR). By additional screening of a human retina cDNA library, we isolated another type of transcript with a 5' UTR different from that of the previously reported type. Genomic sequencing of the ISLR gene revealed that these two types of transcripts, ISLR-1 and ISLR-2, originated from the same gene but are composed of different first exons. Because the entire open reading frame is contained in the second exon, these two transcripts produce the same protein. Radiation hybrid mapping linked the ISLR gene to AFM248yh1, which is in the critical region of Bardet-Biedl syndrome type 4 (BBS4) on chromosome 15. Sequence analysis of the ISLR gene in five BBS4 patients, however, showed no mutations, although a few polymorphic changes were detected. Cloning of the mouse homolog of ISLR (Islr) revealed that the predicted protein consists of 428 amino acids, 86% of which are identical to those of ISLR. The Islr gene was expressed in various mouse tissues, including retina, in which Islr mRNA was detected in the ganglion cell layer, the inner nuclear layer, and the inner segment of the photoreceptor.

Animals↗

Study of the association between the serotonin transporter gene regulatory region polymorphism and personality traits in a Japanese population.

Recently a relationship between serotonin transporter transcriptional control region (5-HTTLPR) polymorphism and anxiety related personality traits in Caucasians was reported. We performed PCR of DNAs from the blood for determining the 5-HTTLPR genotypes of 191 Japanese subjects, which were medical staff and students, and obtained Revised NEO Personality Inventory (NEO-PI-R) and the Temperament and Character Inventory (TCI) in 144 subjects. The association was analyzed by one-way ANOVA. The present study demonstrated that allelic frequency of 5-HTTLPR (s allele frequency was 0.785) in our subjects was considerably different from that in Caucasians. No significant differences were found in the anxiety-related personality traits among genotypes, while cooperativeness in TCI showed a significant difference among genotypes. The property of 5-HTTLPR may not be reflected directory on the personality inventories.

Adult↗

Phylogenetic relationships of symbiotic methanogens in diverse termites.

Termites harbor symbiotic microorganisms in their gut which emit methane. The phylogeny of the termite methanogens was inferred without cultivation based on nucleotide sequences of PCR-amplified 16S ribosomal RNA genes. Seven methanogen sequences from four termite species were newly isolated, and together with those previously published, these sequences were phylogenetically compared. The termite methanogen sequences were divided into three clusters. Two clusters of sequences, derived from the gut DNA of so-called higher termites, were related to methanogens in the orders Methanosarcinales or Methanomicrobiales. All of the sequences in the case of lower termites were closely related to the genus Methanobrevibacter. However, most of the termite symbionts were found to be distinct from known methanogens. They are not dispersed among diverse methanogen species, but rather formed unique lineages in the phylogenetic trees.

Animals↗

Endoscopic lithotripsy with the holmium:YAG laser.

BACKGROUND AND OBJECTIVE: The holmium:YAG (Ho:YAG) laser can be used not only for soft tissue but also for hard tissue such as urinary calculi. The objective of this study was to assess the usefulness of the Ho:YAG laser for endoscopic lithotripsy in patients with urinary tract stone. STUDY DESIGN/MATERIASL AND METHODS: Of 102 procedures performed among 96 patients, 88 were transurethral ureterolithotripsy (TUL), seven were percutaneous nephrolithotripsy, and seven were transurethral cystolithotripsy. Six patients had bilateral stones. The fragments were reduced as much as possible with the Ho:YAG laser. RESULTS: The efficacy rate of the 102 lithotripsy procedures was 93%. With respect to the effect of TUL, the efficacy rates of 40 procedures for the proximal ureter, 18 procedures for the midureter, and 30 procedures for the distal ureter were 85%, 94%, and 100%, respectively. CONCLUSION: The Ho:YAG laser produced a sufficiently strong lithotripsy force on all stones. The results of this study indicate that lithotripsy of urinary tract stones with the Ho:YAG laser can achieve a clinical outcome equivalent to or exceeding that of pulsed dye laser lithotripsy. The Ho:YAG laser is a multipurpose laser and thus is a cost effective and very useful means for endoscopic lithotripsy of urinary tract stones.

Adolescent↗

Nitric oxide increases the amount of murine cytomegalovirus-DNA in mice latently infected with the virus.

At 5 wk after the intraperitoneal infection of murine cytomegalovirus (MCMV) in adult (C3H/He x BALB/c) F1 (CBF1) mice, MCMV-DNA was noted mainly in the salivary glands (SG). Since graft-versus-host reaction (GVHR) is well known as a major risk factor for CMV reactivation, parental BALB/c spleen cells were then intravenously transferred to these mice to induce GVHR. A high copy number of full-length MCMV-DNA was thus observed in the lungs as well as the hearts and livers at 4 to 6 wk after the cell transfer, whereas the copy numbers in SG after the cell transfer were comparable to those before the transfer. It was therefore suggested that the amount of MCMV-DNA noted in these organs had been increased by GVHR. However, no transcripts of MCMV-DNA could be detected. Since a marked expression of mRNA of inducible nitric oxide synthetase (iNOS) was noted in the lungs and the hearts during the course of GVHR, the role of NO in the increase of MCMV-DNA after the cell transfer was next examined. The administration of L-arginine, a substrate for NO, increased the amount of MCMV-DNA in the lungs and the hearts after the induction of GVHR. In contrast, the material which suppressed iNOS induction inhibited the emergence of MCMV-DNA. Therefore, the NO generated during the course of GVHR increased the amount of the viral DNA in the lungs and the hearts of the mice latently infected with MCMV. If the increase in the amount of viral genome is the initial step of viral reactivation from the latent state, then NO would thus trigger the initial step of the reactivation of the DNA virus. As the lungs are the major organ to produce NO after systemic stimulation, the observations of this study may explain why the lungs are the major site of CMV latency and why GVHR triggers CMV reactivation. These findings are thus considered to demonstrate that NO plays a novel role in viral infection.

Animals↗

Surgical resection of intracardiac gastrinoma.

There has been only one previous report of an intracardiac gastrinoma causing Zollinger-Ellison syndrome. In this communication we describe the successful surgical resection of a gastrinoma located in the interventricular septum using cardiopulmonary bypass, blood cardioplegia, and mild hypothermia. Preoperative evaluation and histologic examination of the resected tumor strongly suggest that this was a primary intracardiac gastrinoma.

Cardiopulmonary Bypass↗

The role of intestinal bacterial flora in the tuning of the T cell repertoire.

The role of the intestinal bacterial flora on the Vbeta repertoire was examined using the gnotobiotic murine model. The ratio of Vbeta6-positive T cells in the periphery of DBA/2 mice under SPF conditions was only 2.2% (mean, n = 4), since the cells were eliminated by the endogenous superantigen Mls(a). However, the ratio in germ-free (GF) mice was 31.7%. Similarly, the contamination of the GF Mice with the intestinal flora from SPF mice reduced the ratio of Vbeta6 in GF mice from 22.9% to 13.7%. In contrast, in BALB/c mice (Mls(b)) in which Vbeta6 cells do not react with this endogenous superantigen, the ratio of Vbeta6 cells do not react with this endogenous superantigen, the ratio of Vbeta6 of SPF mice (15.4%, mean, n = 3) was found to be comparable to that of GF mice (15.6%, n = 3). These data suggested that the absence of intestinal flora deteriorated a part of the Mls(a) determinant, which reacted with the Vbeta6 T cells and thereby eliminated them, thus resulting in an increase of these cells in GF mice. Moreover, the alloantigenicity of minor histocompatible alloantigen(s) (mHAg) in SPF mice, which was detected in H-2 identical MLR experiments and a murine graft-versus-host (GVH) model, was reduced in GF and decontaminated SPF mice, thus indicating that the intestinal flora upregulated the mHAg including a part of Mls determinant. These results therefore suggest that the intestinal flora plays a role in the upregulation of mHAg including a part of endogenous superantigen and the consequent tuning of the Vbeta repertoire.

Animals↗

Postoperative chemo-endocrine treatment with mitomycin C, tamoxifen, and UFT is effective for patients with premenopausal estrogen receptor-positive stage II breast cancer. Nishinihon Cooperative Study Group of Adjuvant Therapy for Breast Cancer.

The effectiveness of combining mitomycin C (MMC), tamoxifen (TAM), and 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) was evident in patients with estrogen receptor-positive (ER+) breast cancers. UFT, an oral preparation of tegafur and uracil at a molar ratio of 1:4, was reported to have higher antitumor effects than tegafur alone for patients with breast cancer. Therefore, the combined chemotherapy of MMC, TAM and UFT may possibly be effective for breast cancer. From 1988 to 1991. we studied the effects of postoperative adjuvant therapy for Japanese women with stage 11 breast cancer, all seen at 71 institutions in western areas of Japan. Five hundred and ninety four patients with stage II primary breast cancer who had undergone curative surgery, including total mastectomy and axillary lymph node dissection, were enrolled. On the day of surgery, each patient was given 13 mg/m2 of MMC intravenously. Patients with ER+ tumors were then assigned to group A or group B. Group A received 30 mg/day of TAM given orally from postoperative 2 weeks, for 2 years. Group B was additionally given an oral dose of 300 mg/day of UFT for 2 years, given concomitantly with 30 mg/day of TAM. Patients with ER- tumors were assigned to group C or group D. Group C were prescribed 300 mg/day of UFT, orally, from postoperative 2 weeks for 2 years, and group D were additionally given an oral dose of 30 mg/day of TAM together with 300 mg/day of UFT. There were no differences among the groups regarding prognostic factors or doses of MMC and TAM in ER+ patients and MMC and UFT in ER- patients. Toxicity rates for leukopenia, anorexia, and nausea/vomiting were higher in group B than in group A patients. There were no statistical differences in the overall survival and disease-free survival times between groups A and B, or groups C and D, for all eligible cases. In a retrospective subgroup analysis using Bonferroni's adjustments, the additional effect of UFT on the combined treatment of MMC and TAM lengthened the disease-free survival time for patients with premenopausal ER+ cancers (corrected P value by Bonferroni's adjustments <0.05). Multivariate analysis showed that effects of the combined treatment of MMC, TAM, and UFT was significantly related to the menopausal status (P<0.01). Our findings show that postoperative ingestion of MMC, TAM, and UFT was effective for patients with premenopausal ER+ stage II breast cancer.

Adult↗

Regional cerebral blood flow abnormalities in chronic solvent abusers.

This study aimed to reveal regional abnormalities of cerebral blood flow (CBF) and their relation to amotivational syndrome which causes poor social prognosis in solvent abusers Sixteen chronic solvent abusers (12 males and four females) along with five normal subjects underwent single photon emission computed tomography with N-isopropyl-p[123I]iodoamphetamine. The patients received a clinical evaluation with the Scale for the Assessment of Negative Symptoms. Using a semiquantitative method (normalized by the parietal cortex count), patients showed a statistically significant decrease in regional cerebral blood flow (rCBF) in the bilateral prefrontal cortices (P<0.01). In addition, the severity of hypoperfusion in the bilateral prefrontal cortices was related to the degree of severity of the avolition-apathy scale on SANS (left; P<0.05, right; P<0.01) even after excluding the effect of antipsychotics. These results suggest that rCBF abnormalities, especially in the prefrontal cortex, develop in chronic solvent abusers, and that this frontal hypoperfusion may be a biological basis of amotivational syndrome.

Adolescent↗