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Biomedical subjects

Osamu Sakai

Publications and source records attributed to Osamu Sakai.

At least 19 recordsLinked to original sources
PubMed2006

Exploration of orally available calpain inhibitors 2: peptidyl hemiacetal derivatives.

We previously reported a potent calpain inhibitor 1 (SJA6017, N-(4-fluorophenyl)-l-valyl-l-leucinal), which displayed relatively low oral bioavailability (BA). Replacing the metabolically labile aldehyde moiety of 1with more chemically stable warheads, such as a cyclic hemiacetal, hydrazone, and alpha-ketoamide, provided the inhibitors with improved in vitro metabolic stability. Cyclic hemiacetal 2 was the most stable of these compounds. The optimization of 2 led to hemiacetal 8 (SNJ-1715) which exhibited high potency, good aqueous solubility, excellent oral BA, and prolonged plasma half-life in rats. Furthermore, 8 showed neuroprotective efficacy via oral administration in a rat retinal ischemia model.

Administration, Oral↗
PubMed2006

Combined volumetric T1, T2 and secular-T2 quantitative MRI of the brain: age-related global changes (preliminary results).

The combined T1, T2 and secular-T2 pixel frequency distributions of 24 adult human brains were studied in vivo using a technique based on the mixed-TSE pulse sequence, dual-space clustering segmentation and histogram gaussian decomposition. Pixel frequency histograms of whole brains and the four principal brain compartments were studied comparatively and as function of age. For white matter, the position of the T1 peak correlates with age (R2 =.7868) when data are fitted to a quadratic polynomial. For gray matter, a weaker age correlation is found (R2 =.3687). T2 and secular-T2 results are indicative of a weaker correlation with age. The technique and preliminary results presented herein may be useful for characterizing normal as well as abnormal aging of the brain, and also for comparison with the results obtained with alternative quantitative MRI methodologies.

Adult↗
PubMed2006

Epignathus combined with cleft palate, lobulated tongue, and lingual hamartoma: report of a case.

A case of epignathus combined with cleft palate, lobulated tongue, and lingual hamartoma is reported. A newborn female presented with a large skin-covered mass arising from the palate, cleft palate, and lobulated tongue with a soybean-sized lingual lesion. The palatal and lingual masses were removed on the 9th day after birth. A cystic lesion was also found on the nasal septum after removal of the palatal mass; this lesion was resected at its base. Glossoplasty was performed after excision of the lingual lesion. Histologically, the palatal mass was diagnosed as epignathus. The cystic lesion was suspected to be meningothelial tissues on the basis of hematoxylin-eosin (HE) and immunohistochemical staining: Vimentin and epithelial membrane antigen were positive, and factor VIII was negative. The mass of the tongue dorsum was diagnosed as hamartoma. No recurrence of epignathus or evidence of meningocele have been observed after 5 years of follow up.

Abnormalities, Multiple↗
PubMed2006

Lacrimal gland enlargement in sickle cell disease.

Sickle cell disease (SCD) may have ocular complications. We present the a case of a patient with SCD, with an acute painful episode involving the limbs and periorbital region, who also twice developed an unusual complication of recurrent bilateral lacrimal gland enlargement, not previously reported in the medical literature.

Adult↗
PubMed2006

Multispectral quantitative magnetic resonance imaging of brain iron stores: a theoretical perspective.

OBJECTIVES: To review published magnetic resonance imaging (MRI) iron quantification techniques in the context of quantitative MRI and MR relaxation theories. To analyze comparatively and as a function of age the simultaneous measurements of the proton density (PD), the relaxation times (T1 and T2), and the longitudinal to transverse relaxation times ratio (T1/T2) of brain regions known to accumulate iron preferentially. METHODS: Twenty-seven human subjects were scanned with the mixed turbo spin echo pulse sequence, which is multispectral in PD, T1, and T2. Quantitative MRI (Q-MRI) maps of PD, T1, T2, and T1/T2 were generated, and region of interest measurements were performed in 5 brain regions, namely, frontal white matter (WM), genu of corpus callosum, caudate nucleus, putamen, and globus pallidus. RESULTS: Relaxation time measurements are consistent with results of others and provide further confirmation to our basic understanding of the relaxation effects of iron stores in the brain. Specifically, we found that the iron-rich globus pallidus exhibits enhanced T1 and T2 relaxation relative the iron poorer gray matter tissues (caudate nucleus and putamen) and also relative to the WM matter tissues (frontal WM and genu of the corpus callosum). We also observe that under riding this hypothesis-because we do not have independent confirmation-that iron caused relaxation enhancement, are the normal brain aging patterns, which suggest that the brain tissues become wetter with increasing age. Also noted is the virtual removal of age dependence observed for the T1/T2 ratio of WM tissues, further suggesting that this ratio may become of clinical significance in the diagnosis of neoplastic processes as well as for quantifying iron in tissue. CONCLUSIONS: The theoretical underpinnings of published brain iron Q-MRI techniques have been reviewed. We also examined MR relaxation theory essentials in relation to H-proton relaxation phenomena in diamagnetic tissues as well as theoretical extensions to describe relaxation effects in tissues containing iron deposits with a focus on ferritin. Also reported are in vivo Q-MRI results of 27 human brains obtained with a multispectral technique that uses the mixed turbo spin echo pulse sequence and a model conforming Q-MRI algorithms.

Brain↗
PubMed2006

Coronary artery bypass grafting using a bifurcated internal thoracic artery.

Coronary artery bypass grafting was performed successfully on a patient by anastomosing the left internal thoracic artery and its pericardiacophrenic branch to the obtuse marginal and the posterior descending coronary artery, respectively, to form a Y graft. Preoperative angiography of the internal thoracic artery had revealed the presence of an unusually large pericardiacophrenic branch almost the size of the main trunk, which allowed us to plan for bifurcated artery grafting.

Coronary Artery Bypass↗
PubMed2005

Spin disorder on a triangular lattice.

As liquids crystallize into solids on cooling, spins in magnets generally form periodic order. However, three decades ago, it was theoretically proposed that spins on a triangular lattice form a liquidlike disordered state at low temperatures. Whether or not a spin liquid is stabilized by geometrical frustration has remained an active point of inquiry ever since. Our thermodynamic and neutron measurements on NiGa2S4, a rare example of a two-dimensional triangular lattice antiferromagnet, demonstrate that geometrical frustration stabilizes a low-temperature spin-disordered state with coherence beyond the two-spin correlation length. Spin liquid formation may be an origin of such behavior.

Journal Article↗
PubMed2005

Development of sutureless vascular connecting system for easy implantation of small-caliber artificial grafts.

A novel sutureless vascular connecting system, an assembly with a delivery rod, an introducing sheath, and a connecting device, was developed for easy implantation of small-caliber vascular grafts less than 2 mm in internal diameter. A microporous stainless tube (length 2 mm, external diameter 1.6 mm, wall thickness 65 microm, pore diameter 400 microm, pore-to-pore distance 500 microm) was designed to serve as a connecting device. The feasibility of the system was tested using two types of preliminary animal experiments. One animal model consisted of graft implantation into the rat abdominal aorta (1.5 mm in diameter). The connecting device was inserted into the proximal and distal ends of the aorta through the introducing sheath by pushing the delivery rod with the connecting device placed over it. Subsequently, the aortic segments were inserted into both ends of model grafts made of segmented polyurethane (1.8 mm in internal diameter) and were fixed with banding silk threads from the exterior. The procedure was completed within 20 min without requiring specialized microsurgery techniques. Blood leakage and obstruction did not occur. The second model consisted of an end-to-end anastomosis between rabbit common carotid arteries (2 mm in diameter), which was performed within several minutes of blood flow interruption. Scanning electron microscopy demonstrated that the luminal surface of the device was fully covered with endothelial cells (ECs) after 1 week as a result of transluminal ingrowth of native ECs through the micropores in the device. This endothelialization may prevent early thrombus-induced occlusion. This simple and "easy-to-learn" technique will promote the development of small-caliber arterial grafts, and furthermore, it may have potential for clinical application.

Anastomosis, Surgical↗
PubMed2005

Radiological evaluation of cerebral aneurysms in selected clinical presentations.

BACKGROUND AND PURPOSE: Cerebral aneurysms have different presenting features and, to some extent, a variable clinical course based on the pattern of subarachnoid hemorrhage, the circumstance of their discovery, and the anatomy. Thus, the neuroimaging workup must be tailored accordingly to provide accurate diagnosis and optimal follow-up. METHOD: The authors suggest neuroradiological evaluation of patients in the emergency room and in cases of perimesencephalic subarachnoid hemorrhage, aneurysmal pattern of subarachnoid hemorrhage with normal angiography, vascular infundibula, unruptured/incidental aneurysms, infectious aneurysms, dissecting aneurysms, dolichoectatic/fusiform aneurysms, intracavernous aneurysms, and traumatic aneurysms. CONCLUSION: Recent neuroimaging advances have contributed to improvement in diagnostic safety and accuracy, allowing a more diligent patient follow-up, improved patient outcome, and enhanced physician perception and clinical judgment.

Cerebral Angiography↗
PubMed2005

Diffusion-weighted imaging of cerebral malaria.

Cerebral malaria occurs in 2% of patients infected by Plasmodium falciparum. Magnetic resonance imaging findings of small white matter infarcts due to cerebral malaria have been previously reported, however nonspecific. Since diffusion-weighted imaging can differentiate acute embolic infarcts from other chronic or nonspecific white matter lesions, it may aid diagnosis of this illness in patients who travel to endemic areas.

Aged↗
PubMed2005

Impact of MDCT angiography on the use of catheter angiography for the assessment of cervical arterial injury after blunt or penetrating trauma.

OBJECTIVE: The objective of our study was to assess the impact of the increasing use of MDCT angiography in the setting of blunt and penetrating neck trauma on the use of digital subtraction angiography (DSA) at our institution, a level 1 trauma center. MATERIALS AND METHODS: From January 2001 to December 2003, 57 patients were referred for CT angiography or DSA of the neck after blunt or penetrating neck trauma. All CT angiograms were acquired with a 4-MDCT scanner. The patients were divided into three groups on the basis of consecutive 12-month periods (2001, 2002, and 2003), and the initial imaging technique was recorded. The results of CT and digital subtraction angiograms were compared with operative findings and with clinical course, when available. RESULTS: In 2001, 12 patients were referred for imaging: nine patients were evaluated initially with DSA and three patients were evaluated with CT angiography and subsequently with DSA. In 2002 and 2003, 11 and 34 patients, respectively, underwent CT angiography as the initial imaging examination. During these 2 years, no patient underwent DSA as the initial diagnostic test, but five patients underwent DSA after CT angiography for the following indications: evaluation of nondiagnostic CT angiograms (n = 1), confirmation of findings when requested by the clinical service (n = 2), and catheter-guided therapy (n = 2). CONCLUSION: CT angiography has essentially replaced DSA as the study of choice for the initial evaluation of the neck vessels in the setting of blunt or penetrating trauma at our institution. CT angiography is adequate for the initial evaluation, allows appropriate triage of patients to conventional angiography or surgery for appropriate treatment, and can guide conservative management when appropriate.

Adult↗
PubMed2005

Solitary fibrous tumor of the buccal space.

Solitary fibrous tumors are submesothelial mesenchymal fibroblastic tumors that typically occur in relation to parietal or visceral pleura. However, the tumor also occurs in extrapleural sites, including the peritoneum, mediastinum, orbit, and oral cavity. With the advent of immunohistochemical testing, certain tumors may be more readily identifiable; however, the diagnosis often must be reached by histomorphology and imaging studies alone. We describe a case of a solitary fibrous tumor of the buccal space, including clinical presentation, imaging characteristics, gross pathology, and histopathologic description.

Aged↗
PubMed2004

A randomized open-label comparative study of conventional therapy versus mizoribine onlay therapy in patients with steroid-resistant nephrotic syndrome (postmarketing survey).

BACKGROUND: A previous double-blind 24-week clinical trial of mizoribine (MZ) vs placebo in steroid-resistant primary nephrotic syndrome (SRPNS) showed that MZ was more effective than placebo in reducing the rate of deterioration of renal function. The present study was conducted to evaluate the efficacy and safety of MZ in patients with SRPNS after 2 years' treatment. METHODS: A multicenter randomized open-label controlled trial in patients with SRPNS was conducted as a 2-year prospective postmarketing study. RESULTS: There was a significant imbalance in the baseline serum albumin level (s-Alb) between the conventional therapy (CT) and MZ onlay therapy groups. Early dropouts were more frequent in the subset of patients in the CT group having a baseline s-Alb < or =3 g/dl. Therefore, the primary analysis (urinary protein level (UP)-improving effect) was performed using a mixed-effects model, with stratification according to the baseline s-Alb value. The analysis revealed that, in the subset of 34 patients with membranous nephropathy (MN) within the stratum of patients with baseline s-Alb < or =3 g/dl (n = 52), the rate of change (slope of change in the UP level/month), in terms of the log (UP+0.2), was -0.0577 in those allocated to the MZ group and -0.0227 in those allocated to the CT group (P = 0.058). In the stratum of patients with a baseline s-Alb >3 g/dl (n = 97), there were no significant differences in the UP between the two treatment groups. Hence, MZ onlay therapy was not considered to be efficacious in this group of patients. No serious adverse reactions to the drug were observed. CONCLUSIONS: The present study yielded significant results, in that it suggested the possibility that long-term MZ therapy may afford further reduction of the UP, in addition to that obtained following CT, in particular, in MN patients in a severe nephrotic state.

Adult↗
PubMed2004

Anatomic variants and pearls--functional endoscopic sinus surgery.

For successful endoscopic sinus surgery. a clear understanding of the anatomy is vital. Knowledge of the anatomic relationships and variations helps surgeons avoid complications. By applying anatomic knowledge with careful surgical technique, one can maximize patient safety. Basic tenets for endoscopic sinus surgery can be applied to a variety of patients with confidence.

Endoscopy↗
PubMed2003

Exploration of cornea permeable calpain inhibitors as anticataract agents.

To explore cornea permeable calpain inhibitors, four compounds displaying different characteristics were designed and synthesized based on the known potent calpain inhibitor, peptidyl aldehyde SJA6017. Two approaches were adopted; an improvement in the physicochemical properties, and conversion of the active aldehyde. The water-soluble peptidyl aldehyde 1 containing a pyridine ring at the P3 site showed a modest inhibition against calpains and an improvement of corneal permeability in comparison with SJA6017. Replacement of the aldehyde of SJA6017 by an alpha-ketoamide provided compound 2 that was approximately equipotent with SJA6017, but it was extremely water-insoluble. However, compound 3, in which the aldehyde was converted into a cyclic hemiacetal, proved to be a less potent calpain inhibitor than SJA6017, but demonstrated excellent transcorneal permeability. Further modification generating the cyclic hemiacetal 4 containing a thiourea linker between the P3 and P2 sites exhibited potent inhibitory activities, high cornea permeability and excellent efficacy in the rat lens culture cataract model.

Aldehydes↗
PubMed2003

Structure-activity relationship study and drug profile of N-(4-fluorophenylsulfonyl)-L-valyl-L-leucinal (SJA6017) as a potent calpain inhibitor.

Novel N-arylsulfonyldipeptidyl aldehyde derivatives were prepared by DMSO oxidation from the corresponding dipeptide alcohol, and their potencies as calpain inhibitors were evaluated in vitro. Among them, N-(4-fluorophenylsulfonyl)-l-valyl-l-leucinal (8, SJA6017) potently inhibited calpains. 8 also inhibited cathepsin B and L but did not inhibit other cysteine proteases (interleukin 1beta-converting enzyme), serine proteases (trypsin, chymotrypsin, thrombin, factor VIIa, factor Xa), or proteasome. Preliminary cytotoxicity studies of 8 exhibited a relatively safe profile.

Animals↗