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Biomedical subjects

Hiroto Tanaka

Publications and source records attributed to Hiroto Tanaka.

15 recordsLinked to original sources

Hepatic encephalopathy with status epileptics: a case report.

A 62-year-old male with decompensated liver cirrhosis due to hepatitis C virus developed severe hepatic encephalopathy with status epilepticus. The blood ammonia level on admission was more than twice the normal level. Brain computed tomography and magnetic resonance imaging were normal. In addition, electroencephalogram showed diffuse sharp waves, consistent with hepatic encephalopathy. The status epilepticus was resolved after antiepileptic therapy (phenytoin sodium) and treatment for hepatic encephalopathy (Branched chain amino acids). The blood ammonia level normalized with the clinical improvement and the patient did not have a recurrence of status epilepticus after the end of the antiepileptic treatment. Additionally, the electroencephalogram showed normal findings. Thus, we diagnosed the patient as hepatic encephalopathy with status epilepticus. We consider the status epilepticus of this patient to a rare and interesting finding in hepatic encephalopathy.

Amino Acids, Branched-Chain↗

Cargo-binding makes a wild-type single-headed myosin-VI move processively.

Class VI myosin is an intracellular vesicle and organelle transporter that moves along actin filaments in a direction opposite to most other known myosin classes. The myosin-VI was expected to form a dimer to move processively along actin filaments with a hand-over-hand mechanism like other myosin organelle transporters. Recently, however, wild-type myosin-VI was demonstrated to be monomer and single-headed, casting a doubt on its processivity. By using single molecule techniques, we show that green-fluorescent-protein-tagged single-headed, wild-type myosin-VI does not move processively. However, when coupled to 200-nm polystyrene beads (comparable to intracellular vesicles in size) at a ratio of one head per bead, single-headed myosin-VI moves processively with large (40-nm) steps. The characteristics of this monomer-driven movement were different to that of artificial dimer-driven movement: Compared to the artificial dimer, the monomer-bead complex had a reduced stall force (1 pN compared to 2 pN), an average run length 2.5-fold shorter (91 nm compared to 220 nm) and load-dependent step size. Furthermore, we found that a monomer-bead complex moved more processively in a high viscous solution (40-fold higher than water) similar to cellular environment. Because the diffusion constant of the bead is 60-fold lower than myosin-VI heads alone in water, we propose a model in which the bead acts as a diffusional anchor for the myosin-VI, enhancing its rebinding following detachment and supporting processive movement of the bead-monomer complexes. Although a single-headed myosin-VI was able to move processively with a large cargo, the travel distance was rather short. Multiple molecules may be involved in the cargo transport for a long travel distance in cells.

Actins↗

The formulation of the control of an expression pattern in a gene network by propositional calculus.

In this study we model a gene network as a continuous-time switching network. In this model, each gene has a binary state which indicates if the gene expresses or not. We propose a method to control a sequence of expression patterns in the gene network model by adding another continuous-time switching network. By using propositional calculus, we will show that the control problem can be formulated as a mixed-integer linear programming problem with linear constraints.

Animals↗

The neck domain of myosin II primarily regulates the actomyosin kinetics, not the stepsize.

In order to study the role of the neck domain of myosin in muscle contraction, we measured the steps of individual myosin II molecules engineered to have no neck domain (light chain-binding domain) by optical trapping nanometry. The actin filament and myosin cofilaments interacted on a glass surface to minimize the angle between them, and to minimize the interaction between myosin and the glass surface. The results showed that the average myosin stepsize did not change much when the neck domain was removed, but the sliding velocity decreased approximately fivefold. Furthermore, the duration of steps for neckless myosin was several times longer at saturated ATP concentration, indicating that the slower velocity was due to a slower dissociation rate of myosin heads from actin. From these data, we conclude that the neck domain of myosin-II primarily regulates the actomyosin kinetics, not the mechanics.

Actins↗

Autoimmune hepatitis triggered by acute hepatitis A.

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (X320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.

Acute Disease↗

Mutations in hepatitis B virus core regions correlate with hepatocellular injury in Chinese patients with chronic hepatitis B.

AIM: To elucidate the relationship between the frequency of core mutations and the clinical activity of hepatitis B virus (HBV)-related liver disease and to characterize the amino acid changes in the core region of HBV. METHODS: We studied 17 Chinese patients with chronic hepatitis B according to their clinical courses and patterns of the entire core region of HBV. RESULTS: Amino acid changes often appeared in the HBV core region of the HBV gene in patients with high values of alanine aminotransferase (ALT) or with the seroconversion from HbeAg to anti-HBe. The HBV core region with amino acid changes had high frequency sites that corresponded to HLA I/II restricted recognition epitopes reported by some investigators. CONCLUSION: The core amino acid changes of this study occur due to influence of host immune system. The presence of mutations in the HBV core region seems to be important for predicting the clinical activity of hepatitis B in Chinese patients.

Alanine Transaminase↗

Combination hepatic arterial infusion therapy is effective for ocular melanoma metastasis to the liver.

Regional treatments including chemotherapy have been applied to patients with malignant melanoma metastasis to the liver in clinical trials, but with limited efficacy. To improve efficacy, combination therapy may be beneficial. We had a case of multiple liver metastasis from right ocular malignant melanoma. The primary melanoma was surgically resected, and combination hepatic arterial infusion (HAI) therapy using dacarbazine, nimustine, vincristine (DAV), and cisplatin was applied to the metastatic focus. After HAI, marked regression of the liver metastatic focus was observed. Unfortunately, the patient passed away due to involvement of thrombotic thrombocytopenic purpura 9 months after the initial consultation, however, aggravation of the liver metastatic focus was not observed. Combination HAI therapy may have a potent therapeutic effect on malignant melanoma metastasis to the liver, and our regimen using DAV and CDDP may be beneficial to the improvement of prognosis without serious side effects.

Aged↗

A one-headed class V myosin molecule develops multiple large (approximately 32-nm) steps successively.

Class V myosin (myosin-V) was first found as a processive motor that moves along an actin filament with large ( approximately 36-nm) successive steps and plays an important role in cargo transport in cells. Subsequently, several other myosins have also been found to move processively. Because myosin-V has two heads with ATP- and actin-binding sites, the mechanism of successive movement has been generally explained based on the two-headed structure. However, the fundamental problem of whether the two-headed structure is essential for the successive movement has not been solved. Here, we measure motility of engineered myosin-V having only one head by optical trapping nanometry. The results show that a single one-headed myosin-V undergoes multiple successive large (approximately 32-nm) steps, suggesting that a novel mechanism is operating for successive myosin movement.

Actin Cytoskeleton↗

The motor domain determines the large step of myosin-V.

Class-V myosin proceeds along actin filaments with large ( approximately 36 nm) steps. Myosin-V has two heads, each of which consists of a motor domain and a long (23 nm) neck domain. In accordance with the widely accepted lever-arm model, it was suggested that myosin-V steps to successive (36 nm) target zones along the actin helical repeat by tilting its long neck (lever-arm). To test this hypothesis, we measured the mechanical properties of single molecules of myosin-V truncation mutants with neck domains only one-sixth of the native length. Our results show that the processivity and step distance along actin are both similar to those of full-length myosin-V. Thus, the long neck domain is not essential for either the large steps or processivity of myosin-V. These results challenge the lever-arm model. We propose that the motor domain and/or the actomyosin interface enable myosin-V to produce large processive steps during translocation along actin.

Actins↗

Efficient Synthesis of 1-Amino-2-naphthalenecarboxylic Acid Derivatives via a Sequential Michael Addition/Enolate-Nitrile Coupling Route and Its Application to Facile Preparation of 9-Amino Analogues of Arylnaphthofuranone Lignans.

The reaction of 2-(alpha-lithioalkyl)benzonitriles, generated in situ by treatment of 2-alkylbenzonitriles with LDA in diglyme, with alpha,beta-unsaturated carboxylates and nitriles produced 1-amino-3,4-dihydro-2-naphthalenecarboxylates and carbonitriles in 54-98% yields through Michael addition of the lithio nitriles to alpha,beta-unsaturated carboxylic acid derivatives, followed by zinc iodide-promoted intramolecular enolate-nitrile coupling of the resulting enolate intermediates. The dihydronaphthalenecarboxylic acid derivatives were converted to the corresponding 1-amino-2-naphthalenecarboxylic acid derivatives in 43-99% yields on dehydrogenation with palladium on activated carbon in refluxing p-cymene. Subsequently, we showed that, by using a similar reaction sequence, 9-amino analogues of arylnaphthofuranone lignan derivatives {9-amino-4-arylnaphtho[2,3-c]furan-1(3H)-ones} could also be prepared from 2-(arylmethyl)benzonitriles and furan-2(5H)-one in good overall yields (59-61%).

Journal Article↗

Successful treatment of hepatocellular carcinoma with percutaneous ethanol injection therapy and local hyperthermia.

The patient K.I., a 72-year-old male, was admitted to Nishide Hospital in July 1999 for hemodialysis treatment of end-stage chronic renal failure. At the time of his admission, an ultrasound examination of the patient's liver revealed a large mass in the S5-S8 segment. A hepatocellular carcinoma was suspected from the characteristic mosaic pattern seen with ultrasound and the elevation of alpha-fetoprotein in the serum. The patient's condition was considered to be medically inoperable, due to the patient's adaptation to hemodialysis. Furthermore, transcatheter arterial embolization was not indicated due to the patient's history of hypersensitivity to roentgen-contrast materials. An attempt to palliate the malignancy was made with a combination of local hyperthermia and percutaneous ethanol injection therapy. Magnetic resonance imaging revealed that the tumor structure had changed after 10 days of percutaneous ethanol injection therapy and that 2 months later the tumor size had decreased by about 50%. Moreover, the alpha-fetoprotein level had returned to normal by that time. In addition, this treatment did not cause any disturbance in the liver function. The patient tolerated treatment well. A combined treatment of local hyperthermia with percutaneous ethanol injection therapy appears to be useful in the management of hepatocellular carcinomas, especially in cases in which more aggressive treatment is not acceptable.

Aged↗

Immune-related effects of local hyperthermia in patients with primary liver cancer.

BACKGROUND/AIMS: To investigate immune-related effects of local hyperthermia (HT) with hepatocellular carcinoma (HCC). METHODOLOGY: Immune status after 7 HT was studied in 11 patients (M/F - 9/2; 1st group). The effects were also evaluated during one HT session in 4 of those pts (M/F - 4/0; 2nd group). The HT treatment was performed by means of an 8-MHz capacitive heating device, Thermotron RF8 (Japan). The mean time of one HT session was 60 min, HT was performed 1-2 times a week. In both groups the percentage of T and B cells, CD4+, CD8+ subsets of T cells, the CD4/CD8 ratio and activation of NK cells were evaluated. RESULTS: In the 1st group, CD4/CD8 ratio was decreased significantly (p < 0.05), whereas the relative amount of CD4+ T cells showed a tendency to decrease (p=0.063), and CD8--to increase (p=0.088). An activation of NK cells was observed in patients who had a low or normal pretreatment level of activation. In the 2nd group, there was a significant decrease in the CD4/CD8 ratio by the end of the treatment (p < 0.05) and increased activity of NK cells as early as 20 min after the onset of HT (p < 0.05). CONCLUSIONS: Our results suggest that HT stimulates the immunity of cancer patients by several means and therefore may exhibit indirect anticancer effect. In addition, activation of NK cells by HT may be associated with improved quality of life.

Aged↗