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Biomedical subjects

T Ohtsuka

Publications and source records attributed to T Ohtsuka.

At least 19 recordsLinked to original sources
PubMed2006

Methylation-induced silencing of ASC and the effect of expressed ASC on p53-mediated chemosensitivity in colorectal cancer.

Tumor suppressor p53 is known to play a crucial role in chemosensitivity in colorectal cancer. We previously demonstrated that an apoptosis-associated speck-like protein, ASC, is a p53-target gene which regulates p53-Bax mitochondrial apoptotic pathway. ASC is also known to be a target of methylation-induced gene silencing. An inactivation of ASC might thus cause resistance to chemotherapy, and if this is the case, then the expression of ASC would restore the chemosensitivity. The aim of this study was to clarify this hypothesis. ASC was methylated in 25% of all resected specimens in patients with colorectal cancer; however, ASC methylation did not always correspond to a lack of ASC protein. When expressed in colon cancer cells, in which ASC is absent due to methylation, ASC was found to enhance the chemosensitivity in a p53-dependent manner. In p53-null cells, ASC increased the p53-mediated cell death induced by p53-expressing adenovirus infection. Our data suggest that the methylation-induced silencing of ASC might cause resistance to p53-mediated chemosensitivity in colorectal cancer. The gene introduction of ASC may thus restore such chemosensitivity, and this modality may therefore be a useful new treatment strategy for colorectal cancer.

Antineoplastic Agents↗
PubMed2005

Effects of barbiturates on ATP-sensitive K channels in rat substantia nigra.

ATP-sensitive K channels are widely expressed in cytoplasmic membranes of neurons, and they couple cell metabolism to excitability. They are thought to be involved in neuroprotection against cell damage during hypoxia, ischemia and excitotoxicity by hyperpolarizing neurons and reducing excitability. Although barbiturates are often used in patients with brain ischemia, the effects of these agents on neuronal ATP-sensitive K channels have not been clarified. We studied the effects of thiopental and pentobarbital on surface ATP-sensitive K channels in principal neurons of rat substantia nigra pars compacta. Whole cell voltage- and current-clamp recordings were made using rat midbrain slices. ATP-sensitive K channels were activated by intracellular dialysis with an ATP-free pipette solution during perfusion with a glucose-free solution. When the pipette solution contained 4mM ATP and the perfusing solution contained 25 mM glucose, the membrane current at -60 mV remained stable. When intracellular ATP was depleted, hyperpolarization and an outward current developed slowly. Although thiopental did not affect the membrane current in the presence of ATP and glucose, it reversibly inhibited the hyperpolarization and outward current induced by intracellular ATP depletion at 100 and 300 microM. Thiopental reduced the ATP depletion-induced outward current by 4.7%, 36.7% and 87% at 30, 100 and 300 microM, respectively. The high dose of pentobarbital also exhibited similar effects on ATP-sensitive K channels. These results suggest that barbiturates at high concentrations but not at clinically relevant concentrations inhibit ATP-sensitive K channels activated by intracellular ATP depletion in rat substantia nigra.

Adenosine Triphosphate↗
PubMed2005

Fusiform aneurysm of the vertebral artery presenting with hemifacial spasm treated by microvascular decompression.

We report a rare case of symptomatic hemifacial spasm caused by a fusiform vertebral artery aneurysm. A 59-year-old woman presented with left hemifacial spasm of 18 months duration. Magnetic resonance imaging showed an enlarged a fusiform aneurysm of the left vertebral artery which compressed the seventh cranial nerve at its exit from the caudal pons. Microvascular decompression of the facial nerve with moving of the aneurysm resulted in complete relief of the hemifacial spasm. No enlargement of the aneurysm was shown on follow-up for a period of 6 years.

Aneurysm↗
PubMed2004

Increased prevalence of human parvovirus B19 DNA in systemic sclerosis skin.

BACKGROUND: Human parvovirus B19 is a small, single-stranded DNA virus encoding two structural capsid proteins and a nonstructural protein. It is the aetiological agent of erythema infectiosum and transient aplastic crisis in patients with haemolytic anaemia, and has been associated with fetal death, arthritis and chronic anaemia. In recent years, the possible involvement of parvovirus B19 in systemic sclerosis (SSc) has been reported. OBJECTIVES: To determine whether human parvovirus B19 DNA can be detected in SSc skin tissue specimens. METHODS: Normal subjects (n = 97) and patients with SSc (n = 48), systemic lupus erythematosus (n = 16), dermatomyositis (n = 8), morphoea (n = 6) and graft-versus-host disease (n = 8) were studied. Crude DNA was extracted from skin tissue specimens. We attempted to determine whether human parvovirus B19 could be detected in the skin of SSc using nested polymerase chain reaction (PCR). PCR amplification was performed with specifically designed first and second primer pairs for parvovirus B19 DNA. RESULTS: After the first PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated in comparison with that in normal controls (50 of 97, 52%) (P < 0.01). After the second PCR, the occurrence rate of parvovirus B19 DNA in SSc skin tissues (36 of 48, 75%) was significantly elevated compared with that in normal controls (53 of 97, 55%) (P < 0.02). The occurrence rates in the other diseases showed no significant difference from that in normal controls. CONCLUSIONS: The increased prevalence of human parvovirus B19 DNA in SSc skin showed the possibility that the virus may be involved in the formation of skin tissue abnormalities in the disease.

Adult↗
PubMed2004

Elevated amount of human papillomavirus 31 DNA in a squamous cell carcinoma developed from bowenoid papulosis.

A 50-year-old woman presented with asymptomatic, multiple black macules on the genitalia for 6 months. She presented multiple, round to irregularly shaped, black macules on her labia major and perineum. A keratotic reddish nodule was found on one of the macules. The results of laboratory investigations showed pancytopenia and a decreased CD4/CD8 ratio. A lymphocyte stimulation test showed a decreased response. The histological examination of a biopsy specimen led us to the diagnosis of bowenoid papulosis (BP) for the macules and squamous cell carcinoma (SCC) for the nodule. The macules and nodule were removed successfully. An elevated amount of HPV DNA was demonstrated in SCC compared with that of BP. The HPV DNA in SCC and BP was shown to be HPV-31. These observations indicated that the elevated amount of HPV-31 DNA could have led to the emergence of SCC from BP under the condition of decreased cellular immunity.

Base Sequence↗
PubMed2002

A new method for digital video documentation in surgical procedures and minimally invasive surgery.

BACKGROUND: Documentation of surgical procedures is limited to the accuracy of description, which depends on the vocabulary and the descriptive prowess of the surgeon. Even analog video recording could not solve the problem of documentation satisfactorily due to the abundance of recorded material. By capturing the video digitally, most problems are solved in the circumstances described in this article. METHODS: We developed a cheap and useful digital video capturing system that consists of conventional computer components. Video images and clips can be captured intraoperatively and are immediately available. The system is a commercial personal computer specially configured for digital video capturing and is connected by wire to the video tower. Filming was done with a conventional endoscopic video camera. A total of 65 open and endoscopic procedures were documented in an orthopedic and a thoracic surgery unit. The median number of clips per surgical procedure was 6 (range, 1-17), and the median storage volume was 49 MB (range, 3-360 MB) in compressed form. The median duration of a video clip was 4 min 25 s (range, 45 s to 21 min). Median time for editing a video clip was 12 min for an advanced user (including cutting, title for the movie, and compression). The quality of the clips renders them suitable for presentations. CONCLUSION: This digital video documentation system allows easy capturing of intraoperative video sequences in high quality. All possibilities of documentation can be performed. With the use of an endoscopic video camera, no compromises with respect to sterility and surgical elbowroom are necessary. The cost is much lower than commercially available systems, and setting changes can be performed easily without trained specialists.

Documentation↗
PubMed2002

The polymorphism of telomerase RNA component gene in patients with systemic sclerosis.

BACKGROUND: The molecular basis of senescence and immortalization is not still understood, but one hypothesis for which there has recently been much evidence involves the shortening of telomeres. It can be hypothesized that abnormalities of telomerase contribute to the emergence of abnormal fibroblast clones in systemic sclerosis (SSc). OBJECTIVES: To study possible telomere abnormalities with respect to polymorphism of the telomerase RNA component gene. METHODS: Fifty-three patients with SSc and 98 normal controls were studied. Polymerase chain reaction was used to amplify 598 bp of the telomerase RNA component gene. Amplified fragments were digested with restriction enzyme BsrDI. RESULTS: The frequency of the A allele in SSc (41.5%) showed no significant difference from that in the normal controls (32.1%). The frequency of the A/A alleles in SSc (18.9%) was significantly higher than in normal controls (5.1%), compared with G/G (35.8% and 40.8%, respectively; P < 0.02), G/A (45.3% and 54.1%, respectively; P < 0.01) and G/G plus G/A (81.1% and 94.9%, respectively; P < 0.01). CONCLUSIONS: These results showed the possible involvement of a telomerase abnormality in the emergence of abnormal fibroblast clones in SSc skin-derived fibroblasts.

Adolescent↗
PubMed2002

The polymorphism of transforming growth factor-beta1 gene in Japanese patients with systemic sclerosis.

BACKGROUND: Transforming growth factor (TGF)-beta has been shown to be a potent stimulator of collagen production by fibroblasts, and could play a role in the pathogenesis of systemic sclerosis (SSc). OBJECTIVE: To study the possible involvement of TGF-beta1 gene polymorphism in Japanese patients with SSc. METHODS: Fifty-nine patients with SSc and 110 normal subjects were studied. Genomic DNA was extracted from skin tissues, and was amplified in a thermal cycler, generating a TGF-beta1 gene fragment with a size of 294 bp. The T to C transition at T869C (Leu10Pro) and the G to C transition at G915C (Arg25Pro) were identified by digestion with MspA1I and BglI, respectively. RESULTS: At T869C (Leu10Pro), the frequency of the C allele in SSc (65.3%) was significantly higher than in normal controls (50.5%) (P < 0.01). SSc showed C/C allele 42.4%, C/T 45.8% and T/T 11.2%. Normal controls showed C/C allele 26.4%, C/T 48.2% and T/T 25.5%. The frequency of the C/C allele in SSc was significantly higher than in normal controls, in comparison with the T/T allele (P < 0.02), but no significant difference was found between the frequency of the C/C allele vs. the C/T allele. The frequency of the C/C allele showed no significant difference between diffuse and limited SSc. At G915C (Arg25Pro), all the normal controls and SSc patients showed only the G/G allele. These results are different from a previous study in which the frequency of the T/T allele was high in SSc at T869C (Leu10Pro). CONCLUSIONS: This discrepancy may indicate that Japanese patients with SSc show a different genetic predisposition to TGF-beta1.

Adolescent↗
PubMed2002

Beneficial effect of replacing of angiotensin-converting enzyme inhibitor with angiotensin II antagonist for heart failure patients.

OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitors and beta-blockers improve prognosis inpatients with chronic heart failure. Some patients, however, show little response to combined treatment with an ACE inhibitor and a beta-blocker. In addition, the ACE inhibitor cannot completely suppress angiotensin II production. Our objective was to examine whether replacing the ACE inhibitor with an angiotensin II antagonist can improve the condition of patients with chronic heart failure. METHODS: In 11 patients with chronic heart failure treated with an ACE inhibitor and a beta-blocker, who have had severe left ventricular dysfunction or high plasma level of natriuretic peptides, left ventricular dimension, and fractional shortening, plasma atrial and brain natriuretic peptide (ANP and BNP) levels were determined before and 3 months after the change of treatment. RESULTS: After substituting the ACE inhibitor with an angiotensin II antagonist, patients showed New York Heart Association functional class improvement, and significant decrease in left ventricular dimension and BNP. CONCLUSION: In patients with severe chronic heart failure treated with an ACE inhibitor and a beta-blocker, replacing the ACE inhibitor with an angiotensin II antagonist may be effective. However, this has to be confirmed by an adequately powered randomized controlled study.

Adult↗
PubMed2002

[Surgical management of acute empyema].

Basic principles apply to the management of all forms of acute empyema: investigation and treatment of the underlying infection, drainage of purulent collection, obliteration of the space, and treatment of the associated intercurrent medical conditions. From July 1999 to May 2001, we performed surgical treatment in 11 patients for acute empyema. There were 4 cases of the fibrinopurulent phase and 7 cases of the organizing phase. Surgical procedure was 7 open thoracotomies and 4 thoracoscopies. The mean operating time was 154.2 +/- 36.6 minutes and blood loss during surgery was 344.7 +/- 274.8 ml. There was no procedure-related morbidity. In conclusion, early aggressive surgical approach is a feasible method for treatment of acute empyema.

Acute Disease↗
PubMed2001

Hemodynamic responses to intrapleural insufflation with hemipulmonary collapse.

BACKGROUND: The hemodynamic effects of carbon dioxide (CO2) insufflation with hemipulmonary collapse were studied in consecutive thoracoscopic harvests of the left or right internal mammary artery (IMA), which were used for video-assisted coronary artery bypass grafting. METHODS: Thirty-eight patients (30 male, eight female) with a mean age of 69.5 +/- 11.5 years were selected, and 33 left and five right IMA were harvested thoracoscopically. After hemipulmonary collapse was established by single-lung ventilation, low-flow (2-3 L/min) CO2 was delivered at a constant intrapleural pressure of 8-10 mmHg. Using electrocardiography, a radial arterial catheter, a Swan-Ganz catheter, and transesophageal echocardiography, we obtained values for seven hemodynamic variables. Baseline data were collected during bilateral lung ventilation. Each variable was then measured during hemipulmonary collapse and insufflation. The significance of any changes was established with Student's t-test after correcting for baseline differences. RESULTS: Insufflation facilitated IMA harvest by expanding the pleural space between the anterior chest wall and heart. Mean insufflation times were 40.8 +/- 12.2 min on the left and 33.5 +/- 8.5 min on the right. Significant increases from the baseline values were observed in the mean central venous pressure (L:4.7-9.0 mmHg, R: 5.1-14.0 mmHg, p < 0.05), the pulmonary arterial pressure (L: 11.3-17.3 mmHg, R: 12.1-19.9 mmHg, p < 0.05), and the pulmonary capillary wedge pressure (L: 7.2-10.5 mmHg, R: 6.5-10.0 mmHg, p < 0.05). On the right, but not on the left, slight decreases were noted in the mean arterial pressure and cardiac index (71.3-62.6 mmHg, 2.01-1.76 L min-1 m-2, p < 0.05). CONCLUSIONS: The hemodynamic effect resulting from one-lung collapse plus low-flow CO2 insufflation at 8-10 mmHg for 30-40 min is mild in both hemithoraces, although the impact is greater on the right.

Aged↗
PubMed2001

Design and synthesis of novel benzofurans as a new class of antifungal agents targeting fungal N-myristoyltransferase. Part 1.

Potent and selective Candida albicans N-myristoyltransferase (CaNmt) inhibitors have been identified through optimization of a lead compound 1 discovered by random screening. The inhibitor design is based on the crystal structure of the CaNmt complex with compound (S)-3 and structure-activity relationships (SARs) have been clarified. Modification of the C-4 side chain of 1 has led to the discovery of a potent and selective CaNmt inhibitor 11 (RO-09-4609), which exhibits antifungal activity against C. albicans in vitro.

Acyltransferases↗
PubMed2001

Roles of the basic helix-loop-helix genes Hes1 and Hes5 in expansion of neural stem cells of the developing brain.

Neural stem cells, which differentiate into neurons and glia, are present in the ventricular zone of the embryonal brain. The precise mechanism by which neural stem cells are maintained during embryogenesis remains to be determined. Here, we found that transient misexpression of the basic helix-loop-helix genes Hes1 and Hes5 keeps embryonal telencephalic cells undifferentiated although they have been shown to induce gliogenesis in the retina. These telencephalic cells later differentiate into neurons and astroglia when Hes expression is down-regulated, suggesting that Hes1- and Hes5- expressing cells are maintained as neural stem cells during embryogenesis. Conversely, in the absence of Hes1 and Hes5, neural stem cells are not properly maintained, generating fewer and smaller neurospheres than the wild type. These results indicate that Hes1 and Hes5 play an important role in the maintenance of neural stem cells but not in gliogenesis in the embryonal telencephalon.

Animals↗
PubMed2001

Synthesis, structure-activity relationships, and pharmacokinetic profiles of nonpeptidic alpha-keto heterocycles as novel inhibitors of human chymase.

We designed nonpeptidic chymase inhibitors based on the structure of a peptidic compound (1) and demonstrated that the combination of a pyrimidinone skeleton as a P3-P2 scaffold and heterocycles as P1 carbonyl-activating groups can function as a nonpeptidic chymase inhibitor. In particular, introduction of heterobicycles such as benzoxazole resulted in more potent chymase-inhibitory activity. Detailed structure-activity relationship studies on the benzoxazole moiety and substituents at the 2-position of the pyrimidinone ring revealed that 2r (Y-40079) had the most potent chymase-inhibitory activity (K(i) = 4.85 nM). This compound was also effective toward chymases of nonhuman origin and showed good selectivity for chymases over other proteases. Pharmacokinetic studies in rats indicated that 2r was absorbed slowly after oral administration and showed satisfactory bioavailability (BA) (T(max) = 6.0 +/- 2.3 h, BA = 19.3 +/- 6.6%, t(1/2) = 35.7 +/- 13.3 h). In conclusion, 2r is a novel, potent, and orally active chymase inhibitor which would be a useful tool in elucidating the pathophysiological roles of chymase.

Animals↗