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Biomedical subjects

Mamoru Suzuki

Publications and source records attributed to Mamoru Suzuki.

15 recordsLinked to original sources

Clinical application of the Harmonic Scalpel to allergic rhinitis.

OBJECTIVE: The Harmonic Scalpel (HS) (Johnson & Johnson K.K.) is a surgical tool that allows cutting and coagulation using ultrasonic mechanical vibrations. Its use in the field of otolaryngology has recently been attracting interest. In this study we applied the HS on the inferior nasal concha using a sword shaped blade ('KATANA'). METHODS: Subjects were 20 patients with intractable, perennial allergies that resisted conservative therapy. Subjective symptoms were evaluated as one of five stages, 'symptoms disappeared' 'markedly improved', 'improved', 'unchanged', and 'aggravated'. RESULTS: At the 12th week, 18 patients (90%) with nasal congestion, 16 (80%) with nasal discharge, and 15 (75%) with sneezing had shown at least 'markedly improved'. CONCLUSION: Based on the improvement in subjective symptoms, local and histopathological findings, the HS is an effective surgical modality for these cases. We believe the HS is a safe and useful tool for nasal surgery.

Adolescent↗

Molecular mechanism of membrane recruitment of GGA by ARF in lysosomal protein transport.

GGAs are critical for trafficking soluble proteins from the trans-Golgi network (TGN) to endosomes/lysosomes through interactions with TGN-sorting receptors, ADP-ribosylation factor (ARF) and clathrin. ARF-GTP bound to TGN membranes recruits its effector GGA by binding to the GAT domain, thus facilitating recognition of GGA for cargo-loaded receptors. Here we report the X-ray crystal structures of the human GGA1-GAT domain and the complex between ARF1-GTP and the N-terminal region of the GAT domain. When unbound, the GAT domain forms an elongated bundle of three a-helices with a hydrophobic core. Structurally, this domain, combined with the preceding VHS domain, resembles CALM, an AP180 homolog involved in endocytosis. In the complex with ARF1-GTP, a helix-loop-helix of the N-terminal part of GGA1-GAT interacts with the switches 1 and 2 of ARF1 predominantly in a hydrophobic manner. These data reveal a molecular mechanism underlying membrane recruitment of adaptor proteins by ARF-GTP.

ADP-Ribosylation Factor 1↗

Calpain and caspase inhibitors protect vestibular sensory cells from gentamicin ototoxicity.

OBJECTIVE: Apoptosis may play an important role in the mechanism of aminoglycoside ototoxicity. Caspases and calpains are regarded to be important factors in the regulation of cell death in the inner ear. We hypothesized that caspase or calpain inhibitors would protect hair cells from aminoglycoside ototoxicity. MATERIAL AND METHODS: In order to test this hypothesis we carried out a pilot study to determine if gentamicin (GM) would induce caspase and calpain immunolabeling in guinea pig hair cells Having confirmed this we carried out the main experiment using guinea pig vestibular organ culture to determine if caspase and calpain would protect the hair cells from GM ototoxicity. RESULTS: Immunoreactivity for caspase-3 and m-calpain was detected in the vestibular sensory cells and ganglia after GM treatment. Both caspase and calpain inhibitors protected hair cells against gentamicin ototoxicity. CONCLUSION: It is suggested that inhibition of apoptosis is essential in order to block aminoglycoside ototoxicity.

Animals↗

Experimental study of speed-dependent positional nystagmus in benign paroxysmal positional vertigo.

OBJECTIVE: One of the clinical characteristics of benign paroxysmal positional vertigo (BPPV) is that the more quickly the head position changes, the more severe the vertigo. This suggests that the velocity of the head change is critical in determining the occurrence and severity of vertigo. The aim of this study was to examine factors determining the symptoms of BPPV using models of canalolithiasis and cupulolithiasis. MATERIAL AND METHODS: Canalolithiasis and cupulolithiasis models were prepared using the bullfrog posterior semicircular canal (PSC). The ampullary nerve discharges were compared between quick and slow positional changes to examine factors determining the symptoms of BPPV. RESULTS: In the canalolithiasis model, the acceleration of the otoconia was greater for the quick positional change. This resulted in a greater discharge with a longer duration. With the slow positional change, the discharges were smaller and shorter. In the cupulolithiasis model, the discharges were sustained and their magnitude did not differ between the quick and slow positional changes. The canalolithiasis model influenced the magnitude of discharge of the PSC depending on the speed of the positional change. CONCLUSION: Canalolithiasis is the more likely mechanism of BPPV, which is characterized by various degrees of vertigo upon kinetic positional change.

Animals↗

Model experiment of benign paroxysmal positional vertigo mechanism using the whole membranous labyrinth.

Whole membranous labyrinths of bullfrogs were used in order to replicate the human vestibule. The posterior semicircular canals (PSCs) were exposed, leaving the remaining membranous labyrinth encapsulated in the otic capsule. Vibration was applied to the surface of the bony capsule using a conventional surgical drill in order to dislodge the otoconia from the utricle. The position of the preparation was controlled so that the dislodged otoconia were attached to the cupular surface. This was regarded as a cupulolithiasis model. The action potentials changed instantaneously according to the gravitational force on the cupula. When the otoconia were dislodged and held within the PSC lumen, the position of the whole preparation was changed so that the otoconia moved back and forth within the canal lumen. This is a model of canalolithiasis. The action potentials changed in combination with the otoconial movement after a latent period. Both cupulolithiasis and canalolithasis are potentially valid mechanisms of benign paroxysmal positional vertigo (BPPV). However, canalolithiasis is the most likely mechanism of BPPV, which is usually characterized by nystagmus of short duration and long latency. A vibratory stimulus was able to detach the otoconia from the utricle, suggesting that mechanical insult could be a possible etiology of BPPV.

Animals↗

[A case of gastric cancer with multiple liver metastasis responding to combination therapy of CPT-11 and CDDP].

A 63-year-old man suffering from advanced gastric carcinoma after distal gastric resection had multiple liver metastases 5 months after the operation. He underwent 3 courses of combination chemotherapy of 5-FU 600 mg/day with CDDP 50 mg/day, etoposide 100 mg/day and Leucovorin 30 mg/day for 5 days (FLEP), but progressive disease (PD) was noted. One additional course of combination chemotherapy with CPT-11 140 mg/day and CDDP 40 mg/day biweekly was performed and a complete response (CR) was noted. After 4 months, recurrence of a liver metastasis on S8 was demonstrated and 2 courses of the same chemotherapeutic regimen were carried out. Over 5 months, recurrence of the liver metastasis showed no change (NC) and resection of S8 of the liver was performed. No recurrence was after 6 months, but the patient died 34 months after the first detection of the occurrence of multiple liver metastases. The combination chemotherapy of CPT-11 with CDDP was also administered to other patients at our outpatient clinic and seems to be useful therapy for improving outcome.

Antineoplastic Combined Chemotherapy Protocols↗

[Malaria].

Explore the source record for details and available documents.

Humans↗

Alternate conformations observed in catalytic serine of Bacillus subtilis lipase determined at 1.3 A resolution.

Bacillus subtilis extracellular lipase (BsL) has an exceptionally low molecular weight (19.4 kDa) for a member of the lipase family. A crystallographic study was performed on BsL in order to design and produce mutant BsL that will be more suitable for industrial uses based on analysis of the three-dimensional structure. Recently, the crystal structure of BsL has been determined at 1.5 A resolution [van Pouderoyen et al. (2001). J. Mol. Biol. 309, 215-226]. In the present study, a new crystal form of BsL which provides diffraction data to higher resolution was obtained and its structure was determined at 1.3 A using the MAD method. It was found that the active-site residue Ser77 has alternate side-chain conformations. The O(gamma) atom of the first conformer forms a hydrogen bond to the N(epsilon) atom of His155, a member of the catalytic triad. In contrast, the second conformer is constructed with a hydrogen bond to the side-chain atom of the adjacent His76. These two conformers presumably correspond to the active and inactive states, respectively. Similar alternate conformations in the catalytic serine residue have been observed in Fusarium solani cutinase determined at 1.0 A resolution and Penicillium purpurogenum acetylxylan esterase at 0.9 A resolution. In addition, a glycerol molecule, which was used as a cryoprotectant, is found to be located in the active site. On the basis of these results, a model for substrate binding in the reaction-intermediate state of BsL is proposed.

Amino Acids↗

Inhibition of mitochondrial and plastid activity of Plasmodium falciparum by minocycline.

We previously reported the superior effect of minocycline against drug-resistant Plasmodium falciparum in vitro. Here, we report that RT-PCR for falciparum parasites treated with minocycline revealed reduced levels of RNA transcripts of the mitochondrion-encoded genes such as the COI and Cyb genes, as well as the plastid-encoded RNA polymerase subunit (rpoB/C) gene. However, we detected no apparent effects of the antibiotic on the transcription of merozoite surface antigen and small subunit rRNA genes encoded by the nucleus. In addition, treatment with chloroquine and pyrimethamine showed no substantial reduction of any RT-PCR products. These findings suggest that tetracycline antibiotics selectively inhibit both mitochondrial and plastid activity.

Animals↗

Structural basis for recognition of acidic-cluster dileucine sequence by GGA1.

GGAs (Golgi-localizing, gamma-adaptin ear homology domain, ARF-interacting proteins) are critical for the transport of soluble proteins from the trans-Golgi network (TGN) to endosomes/lysosomes by means of interactions with TGN-sorting receptors, ADP-ribosylation factor (ARF), and clathrin. The amino-terminal VHS domains of GGAs form complexes with the cytoplasmic domains of sorting receptors by recognizing acidic-cluster dileucine (ACLL) sequences. Here we report the X-ray structure of the GGA1 VHS domain alone, and in complex with the carboxy-terminal peptide of cation-independent mannose 6-phosphate receptor containing an ACLL sequence. The VHS domain forms a super helix with eight alpha-helices, similar to the VHS domains of TOM1 and Hrs. Unidirectional movements of helices alpha6 and alpha8, and some of their side chains, create a set of electrostatic and hydrophobic interactions for correct recognition of the ACLL peptide. This recognition mechanism provides the basis for regulation of protein transport from the TGN to endosomes/lysosomes, which is shared by sortilin and low-density lipoprotein receptor-related protein.

ADP-Ribosylation Factors↗

A case of laryngeal aspergillosis following radiation therapy.

Primary laryngeal aspergillosis is extremely rare. It is commonly seen as a part of a systemic infection involving the respiratory system in an immunocompromised host. Differential diagnosis is important, as the clinical symptoms are similar to those of malignant laryngeal disease. We describe a 73-year-old man with a history of hoarseness. He had a history of radiotherapy for laryngeal squamous cell carcinoma and had a history of diabetes. Direct laryngoscope and biopsy confirmed the diagnosis of aspergillus. We cauterized the lesion with a CO(2) laser. In the present case, irradiation seemed to have played a more important role in the onset of this disease rather than diabetes.

Aged↗

Globus sensation caused by gastroesophageal reflux disease.

OBJECTIVES: This study was designed to examine whether or not gastro esophageal reflux disease (GERD) is implicated in globus sensation. METHODS: The subjects were 25 patients (16 men/9 women; mean age: 51, range 25-69 years) complaining of globus sensation with one or more of four laryngeal findings suspected of having GERD, such as pooling of saliva, erythema of posterior one-third of larynx, inter-arytenoids edema, and granuloma. All 25 patients were administrated a proton pump inhibitor (PPI) for a period of 8 weeks. All were given esophageal endoscopies, laryngoscopes, and questionnaire before and after PPI dosing. The questionnaire survey was conducted to investigate changes in globus sensation and three symptoms specific to GERD including heartburn, regurgitation, and belching. Subjective symptoms were totalled by the over all scores of the three subjective symptoms which served as an index of severity of GERD. RESULTS: Fifty-two percent (13/25) of patients had reflux esophagitis. The esophagitis were improved after PPI administration except one case. The incidences of GERD symptoms were high (heart burn 68% (17/25), belching 49% (10/25) and regurgitation 76% (19/25)), and most of these symptoms ameliorated by PPI administration. The laryngeal findings were improved in all patients. Subjective symptoms were improved in 68% (17/25) of globus patients. The improvement rate of total score (before PPI dosing/after PPI dosing) was compared between the two groups: one with improved globus sensation (17 patients) and the other without (8 patients). The improvement rate was significantly higher in the group with improved globus sensation (P<0.05). This means that globus sensation improved because of the improvement in GERD. CONCLUSION: GERD is therefore concluded to be an inducing factor of globus sensation.

Adult↗

Structural basis for the accessory protein recruitment by the gamma-adaptin ear domain.

The adaptor proteins AP-1 and GGA regulate membrane traffic between the trans-Golgi network (TGN) and endosomes/lysosomes through ARF-regulated membrane association, recognition of sorting signals, and recruitment of clathrin and accessory proteins. The gamma 1-adaptin subunits of AP-1 and GGA possess homologous ear domains involved in the recruitment of accessory proteins, gamma-synergin and Rabaptin-5. The crystal structure of the human gamma 1-adaptin ear domain consists solely of an immunoglobulin-like fold, unlike the alpha-adaptin ear domain. Structure-based mutational analyses reveal a binding site for the accessory proteins that is composed of conserved basic residues, indicating that the recruitment mechanism in gamma 1-adaptin and GGA is distinct from that in alpha-adaptin.

Adaptor Protein Complex gamma Subunits↗

[Clinicopathological study of salivary duct carcinoma].

Salivary duct carcinoma (SDC) was first described by Kleinsesser in 1968 and was classified as an independent entity by the 1991 Revised World Health Organization. It is a rare but highly malignant tumor. We reviewed pathology in 49 cases of salivary adenocarcinoma, and diagnosed 6 cases as SDC. All had a rapidly enlarged mass in the parotid gland. All were men, and 4 involved facial palsy and metastasis to cervical lymph nodes. Fine needle aspiration biopsy was conducted in 3 cases, but none was diagnosed as SDC. Two had chemotherapy, but showed no effect. All underwent surgery, but only 1 survived more than 4 years. Immunohistochemically, none showed s-100 protein. Four showed PCNA and p53 protein. Highly positive cells of PCNA and p53 were found around comedo necrosis.

Adenocarcinoma↗