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Biomedical subjects

Takeshi Masuda

Publications and source records attributed to Takeshi Masuda.

17 recordsLinked to original sources
PubMed2026

Daily low-dose carboplatin or weekly carboplatin plus nab-paclitaxel for concurrent chemoradiotherapy in older patients with locally advanced non-small cell lung cancer (JCOG1914): A randomized phase 3 trial.

BACKGROUND: Daily low-dose carboplatin with concurrent thoracic radiotherapy is the standard treatment for older patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) in Japan. METHODS: This open-label phase 3 trial was conducted at 38 institutions in Japan. Patients aged ≥ 75 years with LA-NSCLC were randomly assigned (1:1) to receive daily carboplatin (30 mg/m2) or weekly carboplatin (area under the curve, 2 mg·min/mL) plus nab-paclitaxel (30 mg/m2) with thoracic radiotherapy. Durvalumab maintenance therapy was recommended after treatment completion. The primary endpoint was overall survival, which was used to assess the non-inferiority of weekly carboplatin plus nab-paclitaxel compared to daily low-dose carboplatin. RESULTS: From December 2020 to March 2024, 124 patients were enrolled (carboplatin arm, 61 and carboplatin plus nab-paclitaxel arm, 63). In the planned interim analysis, the Bayesian predictive probability indicating the non-inferiority of carboplatin plus nab-paclitaxel compared with carboplatin in the final analysis was 8.0%, leading to early study termination for futility. The median overall survival was not estimable in the carboplatin arm; the estimated value in the carboplatin plus nab-paclitaxel arm was 26.1 months (hazard ratio, 1.56; 95% confidence interval, 0.79-3.11; p = 0.200). Two treatment-related and seven non-cancer-related deaths occurred in the carboplatin plus nab-paclitaxel arm. Patients in the carboplatin arm had better quality of life than those in the carboplatin plus nab-paclitaxel arm at 6 weeks (odds ratio, 0.39; 95% confidence interval, 0.18-0.81; p = 0.012). CONCLUSIONS: Daily low-dose carboplatin with concurrent thoracic radiotherapy remains the standard treatment for older patients with unresectable LA-NSCLC in Japan.

Humans↗
PubMed2007

Development of a polymeric matrix metalloproteinase inhibitor as a bioactive stent coating material for prevention of restenosis.

Drug-eluting stents have been developed to prevent restenosis derived from excessive growth of smooth muscle cells (SMCs) after stenting. In almost every case, however, less- or non-biocompatible polymers were selected for the platform material for impregnating drugs on the stent strut. Consideration was given principally to the physical properties of the polymers, such as their adhesion to the strut and the drug dispersibility in the polymeric matrix. In this study, we designed a matrix metalloproteinase inhibitor (MMPI)-derivatized hydrophobic polymer (PMMPI) for use as a bioactive material for stent coating. This was a copolymer of n-butylmethacrylate and a vinyl monomer of synthetic MMPI (N-Hydroxy-5-carboxyethylcarbonyloxy-2(S)-methy-4(S)-(4-phenoxybenzoyl)amino-pentanamide: ONO-M11-335) with a molecular weight of about 32,000 and MMPI content of 45 per molecule. The precursor of the MMPI monomer produced significant activity in temporally inhibiting SMC proliferation without any cellular damage. After coating with the PMMPI, adhesion and proliferation of SMCs were manifestly prevented even when a small amount of MMPI was released from the polymer. The MMPI-immobilized surface may thus be effective for inhibiting both adhesion and proliferation of SMCs, which is the first step toward in vivo experimentation. It is very much expected that coating stent struts with PMMPI containing an appropriate combination of impregnated drugs will provide a powerful tool for prevention of restenosis with little cytotoxicity.

Animals↗
PubMed2007

Discal cysts of the lumbar spine. Report of five cases.

Discal cysts are rare lesions that can result in refractory sciatica. Because they are so rare, their exact origin and details of the clinical manifestations are still unknown. The authors report on five men treated for discal cysts. The mean age of the patients at the time of the surgery was 32 years (range 25-38 years). All patients suffered from lower-extremity pain and the results of the straight leg-raising test were positive in all cases. Three patients reported motor weakness and four had sensory disturbance-symptoms similar to those found in patients with lumbar disc herniation. Magnetic resonance imaging demonstrated spherically shaped extradural lesions of various sizes with low and high signal intensities on T1- and T2-weighted images, respectively. Discography revealed obvious communication between the cyst and the intervertebral disc with reproducible leg pain in all patients. All patients underwent posterior decompression and excision of the cysts either with or without additional discectomy. The radicular symptoms were remarkably improved in all patients immediately after surgery, and no recurrent lesions were noted during follow up.

Adult↗
PubMed2007

Deep vein thrombosis due to migrated graft bone after posterior lumbosacral interbody fusion. Case report.

The authors report the case of an 83-year-old woman with refractory sciatica attributable to isthmic spondylolisthesis at L-5. Her symptoms were successfully improved after posterior lumbar interbody fusion (PLIF) at L5-S1; however, notable swelling in her left leg suddenly developed 2 days postoperatively. Anterior migration of a fragment of bone graft was demonstrated on computed tomography scanning, and there was obvious occlusion of the left common iliac vein (CIV) on magnetic resonance venography. Ultrasonography revealed a thrombus in the left CIV at the site of compression. To prevent a pulmonary embolism during manipulation of the affected vein, an inferior vena cava filter was placed just before excision of the migrated bone fragment. The swelling in the patient's leg subsided quickly after the surgery, and she was treated with heparin and warfarin to prevent recurrent deep vein thrombosis (DVT). Six months after the second surgery, complete restoration of blood flow to the left CIV and no recurrence of DVT were demonstrated on magnetic resonance venography. Especially in elderly patients with degenerative disc disease, excessive curettage and impaction of disc materials during the PLIF procedure may cause migration of bone graft fragments. Surgeons should be aware of the possible vascular complications of PLIF.

Aged, 80 and over↗
PubMed2006

HybGFS: a hybrid method for genome-fingerprint scanning.

BACKGROUND: Protein identification based on mass spectrometry (MS) has previously been performed using peptide mass fingerprinting (PMF) or tandem MS (MS/MS) database searching. However, these methods cannot identify proteins that are not already listed in existing databases. Moreover, the alternative approach of de novo sequencing requires costly equipment and the interpretation of complex MS/MS spectra. Thus, there is a need for novel high-throughput protein-identification methods that are independent of existing predefined protein databases. RESULTS: Here, we present a hybrid method for genome-fingerprint scanning, known as HybGFS. This technique combines genome sequence-based peptide MS/MS ion searching with liquid-chromatography elution-time (LC-ET) prediction, to improve the reliability of identification. The hybrid method allows the simultaneous identification and mapping of proteins without a priori information about their coding sequences. The current study used standard LC-MS/MS data to query an in silico-generated six-reading-frame translation and the enzymatic digest of an entire genome. Used in conjunction with precursor/product ion-mass searching, the LC-ETs increased confidence in the peptide-identification process and reduced the number of false-positive matches. The power of this method was demonstrated using recombinant proteins from the Escherichia coli K12 strain. CONCLUSION: The novel hybrid method described in this study will be useful for the large-scale experimental confirmation of genome coding sequences, without the need for transcriptome-level expression analysis or costly MS database searching.

Algorithms↗
PubMed2006

Prediction of liquid chromatographic retention times of peptides generated by protease digestion of the Escherichia coli proteome using artificial neural networks.

We developed a computational method to predict the retention times of peptides in HPLC using artificial neural networks (ANN). We performed stepwise multiple linear regressions and selected for ANN input amino acids that significantly affected the LC retention time. Unlike conventional linear models, the trained ANN accurately predicted the retention time of peptides containing up to 50 amino acid residues. In 834 peptides, there was a strong correlation (R2 = 0.928) between measured and predicted retention times. We demonstrated the utility of our method by the prediction of the retention time of 121,273 peptides resulting from LysC-digestion of the Escherichia coli proteome. Our approach is useful for the proteome-wide characterization of peptides and the identification of unknown peptide peaks obtained in proteome analysis.

Chromatography, High Pressure Liquid↗
PubMed2005

Spinopelvic alignment in patients with osteoarthrosis of the hip: a radiographic comparison to patients with low back pain.

STUDY DESIGN: A retrospective, age- and sex-matched radiographic study. OBJECTIVES: To investigate the spinopelvic alignment in patients with osteoarthosis of the hip (HOA) and those with low back pain (LBP) and to determine the characteristics and differences in both groups. SUMMARY OF BACKGROUND DATA: Hip-spine syndrome, first described by Offierski and MacNab, is quite an important pathology when treating patients with pain in their low back and lower extremities. However, despite it being a well-known entity, few papers have adequately investigated and assessed the spinopelvic alignment in patients with hip-spine syndrome. METHODS: Sagittal and coronal spinopelvic alignments were investigated in 150 patients with HOA and 150 with LBP using radiographs of the whole spine in both anteroposterior and lateral views. Parameters measured in this study were lumbar lordosis (LL), sacral slope (SS), the shift of the sagittal C7 plumb line, pelvic incidence (PI), and pelvic tilt (PT) on the lateral radiographs. On the anteroposterior (AP) films, lumbar scoliosis, pelvic obliquity, leg length discrepancy, the shift of the coronal C7 plumb line, and Sharp angle were measured. These parameters were compared between the two groups. In patients with HOA, the relationships between Sharp angle and other parameters were also analyzed to clarify the possible influence of sagittal and coronal spinopelvic alignments on HOA without acetabular dysplasia. RESULTS: LL, SS, PI, and PO were found to be less in patients with LBP compared with those with HOA, and there was no significant difference in LS between the two groups. PI was significantly greater in HOA patients and strongly correlated to PT, SS, and LL (i.e., as the PI increased so did the PT, SS, and LL). Sharp angles were also significantly greater in HOA patients and strongly correlated to age, LL and SS (i.e., as Sharp angles increased so did LL and SS); however, age decreased in the hip patients. CONCLUSIONS: These findings suggest that higher PI in the younger individual may contribute to the development of HOA in later life without both lumbar kyphosis and acetabular dysplasia because of the anterior uncovering of the acetabulum. More investigation will be expected to analyze the spinopelvic alignment in patients with hip spine syndrome.

Acetabulum↗
PubMed2005

A prospective evaluation of anesthesia for posterior lumbar spine fusion: the effectiveness of preoperative epidural anesthesia with morphine.

STUDY DESIGN: A prospective, randomized, single-blinded study. OBJECTIVES: To prospectively compare the anesthesia for posterior lumbar spinal fusion between the age- and gender-matched groups with and without preoperative epidural anesthesia with morphine. SUMMARY OF BACKGROUND DATA: To reduce the blood loss, hypotensive anesthesia is frequently used in the spinal fusion. However, in spite of administration of the hypotensive agents, inadequate analgesia during operation often causes unfavorable and unexpected elevation of blood pressure resulting in excessive bleeding. As well, intractable wound pain sometimes occurs after spinal fusion due to inadequate analgesia during surgery. METHODS: Forty cases of posterior lumbar spinal fusion were investigated prospectively. Twenty patients underwent preoperative epidural anesthesia with morphine and sedation by continuous intravenous administration of propofol but without administration of any kind of anesthetics, including intraoperative and/or postoperative epidural anesthesia (Group E). Another 20 patients underwent inhalation general anesthesia with sevoflurane and intermittent intravenous administration of fentanyl without any regional block (Group F). In these groups, dynamics and average mean blood pressure during surgery, blood loss during surgery, postoperative requirement of analgesics, the visual analogue scale, and accuracy of neurologic evaluation immediately after surgery were analyzed. RESULTS: The average mean blood pressure during surgery was significantly lower in Group E than Group F: 57.1 mm Hg and 72.8 mm Hg, respectively. In addition, the dynamics of blood pressure were more stable in Group E than Group F. The blood loss during surgery was significantly less in Group E than in Group F: 546 g and 631 g, respectively. The patients of Group E required analgesics after surgery less frequently, and the rating on the visual analogue scale was significantly lower in Group F on the first, second, and third days after surgery. It was difficult to evaluate the neurologic status accurately in 5 patients of Group F because of the inadequate emergence immediately after surgery. There were no patients in Group E whose neurologic status was unclear because of the paralysis caused by epidural anesthesia. CONCLUSIONS: To combine preoperative epidural anesthesia with other anesthetic procedure for spinal fusion contributes to maintain more stable hypotension during surgery. As a result, it will be possible to lessen the bleeding during surgery. In addition, the postoperative pain was easily controlled with administration of fewer analgesic agents in patients who underwent the epidural anesthesia. The effectiveness of pre-emptive analgesia should be emphasized to diminish the postoperative pain.

Adult↗
PubMed2005

Spinal reconstruction using a cervical pedicle screw system.

Although the cervical pedicle screw system is considered the most effective instrumentation for posterior cervical spine surgery, reports on clinical application are limited because of the unresolved and inherent risk of neurovascular complications. The purpose of this study is to retrospectively evaluate the accuracy of placement and clinical effectiveness of the cervical pedicle screw. The cases of 26 patients were investigated. The average followup was 20 months. All but one patient had simultaneous decompression and fusion of various extent. In these cases, screw placement, alignment of the fused segment, fusion rate, neurologic improvement, and complications were assessed. Using an image intensifier, 134 screws were inserted. Five screws (3.7%) completely perforated and 10 (7.4%) partially perforated. The complete perforations occurred in the first 10 patients. Except for two patients with metastasis, bony union was obtained in all patients without loss of correction. Neurologic impairment also was improved in all patients, and no complications associated with the cervical pedicle screw were seen. Clinical results of the cervical pedicle screw system were excellent with few complications. However, there is the possibility of screw perforation, which could cause neurovascular complications. Increased accuracy of screw insertion is needed to make this instrumentation safer.

Adult↗
PubMed2005

High performance gene delivery polymeric vector: nano-structured cationic star polymers (star vectors).

Nano-structured hyperbranched cationic star polymers, called star vectors, were molecularly designed for a novel gene delivery non-viral vector. The linear and 3, 4 or 6 branched water-soluble cationic polymers, which had same molecular weight of ca. 18,000, were synthesized by iniferter (initiator-transfer agent-terminator)-based photo-living-radical polymerization of 3-(N,N-dimethylamino)propyl acrylamide, initiated from respective multi-dithiocarbamate-derivatized benzenes as an iniferter. All polymers produced polyion complexes 'polyplexes' by mixing with pDNA (pGL3-control plasmid), in which the particle size was ca. 250 nm in diameter [the charge ratio < 2/1 (vevtor/pDNA)] and ca. 150 nm (the charge ratio > 2.5/1), and the zeta-potential was ca. +10 mV (the charge ratio > 1/1). When COS-1 cells were incubated with the polyplexes 12 h after preparation under the charge ratio of 5/1, higher gene expression was obtained as an increase in branching, with a little cytotoxicity. The relative gene expression to the linear polymer was about 2, 5, and 10 times in 3-, 4-, and 6-branched polymers, respectively. The precise change in branching of polymers enabled the control of the gene transfer activity.

Animals↗
PubMed2005

Pyogenic spondylitis in the cervicothoracic junction with high-positioned aortic arch. Case report and review of the literature.

The authors report the case of an 87-year-old woman who suffered from T1-2 pyogenic spondylitis resulting in progressive and severe paraplegia. Debridement and anterior manubrium-splitting fusion were difficult because a high-positioned aortic arch was very close to the infectious lesion. Because adequate intravenous antibiotic agents had nearly resolved the inflammation, the authors undertook anterior debridement and posterior fusion that involved costotransversectomy and the placement of a posterior cervical pedicle screw fixation system. At 1.5 years postoperatively, there were no signs of recurrent infection. Solid osseous union was documented, and the patient's paraplegia had improved. A high-positioned aortic arch will likely interfere with an anterior approach to the cervicothoracic junction. If adequate antibiotic therapy has successfully controlled the spinal infection, anterior debridement and posterior fusion can be conducted in cases involving such anatomical limitations.

Aged↗
PubMed2003

Development of a water-soluble matrix metalloproteinase inhibitor as an intra-arterial infusion drug for prevention of restenosis after angioplasty.

To prevent restenosis after percutaneous transluminal coronary angioplasty (PTCA) and/or stenting of atherosclerotic stenosed arteries, we designed and developed two water-soluble matrix metalloproteinases (MMPs) inhibitors. The first inhibitor was monomeric in type and was chemically synthesized by succinylation of the synthetic MMP inhibitor, N-hydroxy-5-hydroxy-2(S)-methyl-4(S)-(4-phenoxybenzoyl)aminopentanamide (ONO-M11-335). The second inhibitor was polymeric and was a radical copolymer of the vinyl derivative of ONO-M11-335 and a water-soluble monomer, N,N-dimethylacrylamide (DMAAm). For the second inhibitor, NMR analyses and UV-vis spectra measurements showed that the content of the ONO-M11-335 unit in the copolymers (M(n); ca. 10 000 and 20 000 by GPC measurements) was about 8 per molecule. The MMP inhibitors were all highly soluble in water, even under neutral pH. The succinylated derivative markedly inhibited MMP-2, MMP-9, and MMP-12 in vitro, as did ONO-M11-335. In contrast the copolymers, which can maintain effective plasma levels for extended periods by prevention of hepatic uptake, showed a ca. 100-fold reduced inhibition activity. Such water-soluble MMP inhibitors, developed in this study, may potentially be useful as an intra-arterial infusion drug for vascular injury.

Acrylamides↗
PubMed2003

Synthesis and anti-influenza evaluation of orally active bicyclic ether derivatives related to zanamivir.

We synthesized bicyclic ether sialidase inhibitors such as tetrahydro-furan-2-yl, tetrahydro-pyran-2-yl, and oxepan-2-yl derivatives related to zanamivir. These compounds substituted by diol at the C-3' and C-4' positions resulted in the retention of low nanomolar inhibitory activities against not only influenza A virus sialidase but also influenza A virus in cell culture. Compound 11a in particular showed comparable efficacy in vivo relative to that of oseltamivir phosphate.

Administration, Oral↗
PubMed2003

Synthesis and anti-influenza evaluation of polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives.

Polyvalent sialidase inhibitors bearing 4-guanidino-Neu5Ac2en derivatives on a poly-L-glutamine backbone are described. Aiming for a longer retention time of 4-guanidino-Neu5Ac2en (zanamivir) in bronchi and lungs, we focused on supermolecules bearing 4-guanidino-Neu5Ac2en derivatives bound at their C-7 position through noncleavable alkyl ether linkages. We first found that alkylation of the 7-hydroxyl group of sialic acid derivative 8 proceeded smoothly, and produced 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives 13, which exhibited equipotent inhibitory activity against not only influenza A virus sialidase but also influenza A virus in the cell culture. Next, we synthesized poly-L-glutamine bearing 7-O-alkyl-4-guanidino-Neu5Ac2en derivatives linked by amide bonds, 26, which showed enhanced antiviral activity against influenza A virus and more potent efficacy in vivo relative to a monomeric sialidase inhibitor.

Administration, Intranasal↗
PubMed2002

Synthesis and anti-influenza virus activity of 4-guanidino-7-substituted Neu5Ac2en derivatives.

Substitution of 7-OH by small hydrophobic groups on zanamivir resulted in the retaining of low nanomolar inhibitory activities against not only influenza A virus sialidase but also influenza A virus in cell culture. These compounds were prepared by treatment of the corresponding 7-substituted sialic acids derived from 4-modified N-acetyl-D-mannosamine (ManNAc) using enzyme-catalyzed aldol condensation.

Antiviral Agents↗
PubMed2002

Synthesis and anti-influenza virus activity of 7-O-alkylated derivatives related to zanamivir.

A series of 7-alkyl ether derivatives related to zanamivir were synthesized using direct alkylation of the C-7 alcohol of sialic acid. Alkyl ether moiety of less than 12 carbons in length showed low nanomolar inhibitory activity against influenza A virus sialidase. Furthermore, their moiety improved influenza A virus plaque reduction activity compared to zanamivir. However, removal of the 8,9-diol of the 7-O-alkyl derivatives resulted in loss of antiviral potency. This result suggests that 8,9-diol must play an important role in binding with both influenza A and B virus sialidases.

Antiviral Agents↗