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Biomedical subjects

T Yasuda

Publications and source records attributed to T Yasuda.

At least 361 records · Page 20Linked to original sources

Availability of liposomes as drug carriers to the brain.

Phospholipid vesicles, also known as liposomes, were examined for their ability to act as a drug carrier to the brain. 9-Amino-1,2,3,4-tetrahydroacridine (THA), a centrally acting acetylcholinesterase inhibitor, was used as a model drug. THA was encapsulated in dehydration-rehydration vesicles (DRV) composed of egg yolk phosphatidylcholine, cholesterol and dipalmitoyl-phosphatidic acid (molar ratio, 10/10/1) and injected into the heart of mice. The toxicity and side effects of THA were reduced by encapsulation in liposomes. The THA concentration in the mouse brain after injection of THA-encapsulated DRV at a dose of 2 mg/kg remained higher than that of free THA at the same dose. Effective concentration of THA in the brain was also prolonged by the use of liposomes, although accumulation of THA in the spleen and kidney was observed. We, therefore, concluded that liposomes are useful as carriers of drugs to the brain.

Animals↗

Tuberculous tenosynovitis in the elbow joint.

A 74-year-old woman was noted to have a mass lesion near the right elbow joint during medication for pulmonary tuberculosis. After discontinuation of medication, the mass gradually became enlarged with swelling and tenderness of the joint. Radiological evaluation disclosed tenosynovitis with an encapsulated abscess. Microscopic examination and culture of an aspiration biopsy specimen from the abscess showed no microorganisms. However, DNA extracted from the specimen contained mycobacterium tuberculosis DNA, permitting a diagnosis of tuberculous tenosynovitis. Mycobacterium is not always detected in biopsy specimens of tuberculous arthritis and tenosynovitis. In such cases, genetic diagnosis may be of great use.

Abscess↗

[Adjuvant chemotherapy for advanced gastric cancer].

For recent 40 years, many authors reported the results of adjuvant chemotherapy for advanced gastric cancer including 5-fluorouracil, uracil and tegafur, mitomycin C, cytosine arabinoside. OK-432 adriamycin, methotrexate, and cis-pltatin in solitary use of combinations. It is difficult to find a standard effective adjuvant chemotherapy for advanced gastric cancer in these reports. The reasons of this unclearness were as follows; (1) In phase III studies, surgery alone was not a control group in some reports. (2) The number of patients was too small to evaluate statistically. (3) Inter-institutional differences had important roles in the results of multicenter study in the other studies. For the future plans on adjuvant chemotherapy, it is important to make a simple designed protocol, and perform it as a multicenter study including institutions with minimum inter-institutional differences.

Antineoplastic Combined Chemotherapy Protocols↗

Gene transfer with liposomes to the intraocular tissues by different routes of administration.

PURPOSE: To determine whether a reporter gene carried by liposomes can be introduced into the ocular tissues in vivo by different routes of administration. METHODS: Three different kinds of liposomes carrying plasmid DNA with beta-galactosidase gene were applied topically to the eye or were injected into the anterior chamber, subretinal space, and vitreous of adult Wistar rats. Gene expression was detected by enzymatic color reaction using X-gal as a substrate in enucleated eyes 1 day, 1 week, and 1 month after topical application or injection. RESULTS: Topical application could transfer the gene to retinal ganglion cells. Injection into the anterior chamber delivered the gene to the basal layer of the corneal epithelium, ciliary epithelium, stroma of the ciliary body and iris, and retinal ganglion cells. Injection into the vitreous or subretinal space resulted in the expression of the gene in the ciliary epithelium, stroma of the ciliary body and iris, retinal ganglion cells, and retinal pigment epithelial cells. CONCLUSIONS: Efficient and stable transfer of the functional gene could be achieved by liposomes in the cornea, iris, ciliary body, and retina of rats. Liposomes appear to be a promising vehicle for delivering therapeutic genes in vivo to mammalian intraocular tissues.

Administration, Topical↗

A new individualization marker of sweat: deoxyribonuclease I (DNase I) polymorphism.

We confirmed for the first time, both biochemically and immunologically, the existence of deoxyribonuclease I (DNase I) in human liquid sweat. Isoelectric focusing of sweat samples on polyacrylamide gels (pH 3.5 to 5), followed by dried agarose film overlay detection, was used to determine the phenotypes of sweat DNase I. Because this detection method not only had high sensitivity, but also high band resolution, it was possible to determine DNase I types from sweat samples of 50 to 100 microL. Pretreatment of sweat samples with sialidase was essential for typing to enhance markedly the sensitivity accompanied by simplification of the isozyme pattern. The DNase I types in all sweat samples were consistently related to the types found in corresponding blood, urine, and semen samples. DNase I typing could, therefore, provide a novel discriminant characteristic in the forensic examination of sweat.

Biomarkers↗

[A case of hereditary neuropathy with liability to pressure palsies (HNPP) with diabetes mellitus].

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant neuropathy recently reported to be associated with deletion of the peripheral myelin protein-22 (PMP-22) gene. We report a 39-year-old man with recurrent brachial plexopathy and foot drop complicated by uncontrolled diabetes mellitus (DM). Right foot drop occurred at 31 years of the age and the patient subsequently experienced difficulty in raising his right arm. Neurological examination revealed weakness of the right deltoid, biceps muscles and tibialis anterior muscles. Deep tendon reflexes were generally absent. Sensory nerve conduction velocities in th ulnar, median and sural nerves were prolonged. Serum glucose and HB Alc levels were elevated to 468 mg/dl and 12.5%, respectively. Initially, it was difficult to diagnose the neuropathy as HNPP because the patient had poorly controlled diabetes mellitus and was unaware of similar disease in his family. In addition, focal asymmetric motor neuropathy and good recovery can develop in diabetes mellitus, occasionally with recurrence. We were able to make a final diagnosis of HNPP by detecting deletion of the PMP-22 gene region. After the diagnosis was confirmed, we examined the patient's family and found that his father experienced recurrent episodes of bilateral foot drop. This case suggests that gene analysis is sometimes essential in the differential diagnosis of hereditary peripheral neuropathies.

Adult↗

[An operative case of bilateral partial anomalous pulmonary venous return using a direct anastomosis between the right atrial appendage and the superior vena cava].

We have experienced a case of bilateral partial anomalous pulmonary venous return without atrial septal defect. Right upper pulmonary vein returned to the superior vena cava and left upper pulmonary vein returned to the left brachiocephalic vein. This type of bilateral partial anomalous pulmonary venous return was extremely rare, and only 4 such cases have been reported in the Japanese literature. The patient, aged 3 years and 11 months, was successfully operated on, using a direct anastomosis between the right atrial appendage and the superior vena cava. This procedure is considered to be advantageous because both this right atriotomy line and suture line avoid injury of the sinus node and the sinuatrial node artery and no foreign material is used. A decrease in postoperative arrhythmia can also be expected from this procedure.

Anastomosis, Surgical↗

[The preventive effect of weekly high-dose 5-FU infusion (WHF) after resection of hepatic metastasis from colorectal cancer].

Hepatic metastasis is often found even after resection of hepatic metastases from colorectal cancer. This implies that the micrometastasis already existed in residual liver when the resection was performed, and so complete recovery with resection alone is rare. We have been using a weekly high-dose 5-FU HAI (WHF = 5-FU 1,000 mg/m2/5 hrs/qw) since 1991, which has preventive effects for metastasis in residual liver as compared to a group treated without infusion chemotherapy. Hepatectomy was performed in 30 of 113 cases of hepatic metastasis from colorectal cancer during the past 16 years. For comparison, we divided the 30 cases into group A1 (16 cases H1:12, H2:4), which received hepatectomy only, and group A2 (14 cases H1:8, H2:4, H3:2), which additionally received infusion chemotherapy. The 1- and 3-year (cumulative) survival rates were 64.6% and 32.3% in group A1, and 100% and 75.3% in group A2 respectively in which the treatment outcome was significantly higher. The 1- and 3-year recurrence rates were 41.7 and 66.3 in group A1, and 8.3% each in group A2, respectively, which reveals that metastasis in residual liver was controlled in group A2. Other metastases were seen in lung (6 cases), bone (2 cases), hepatic hilar lymph node (3 cases), brain (1 case) and local (3 cases) in group A1, while only one metastasis in each brain and locally was seen in group A2 so far. WHF after resection of hepatic metastasis from colorectal cancer has a preventive effect not only for the recurrence in residual liver but also for other metastases. Therefore, as improvement in the survival rate is expected.

Aged↗

[Hepatic resection with "wrapping therapy" for advanced hepatocellular carcinoma uncontrolled by arterial embolization].

We report a 70-year-old male patient who had successful hepatic resection with "Wrapping therapy" for advanced hepatocellular carcinoma (HCC) uncontrolled by arterial embolization. His laboratory tests were as follows: Alb: 4.7 (g/dl), T. Bil:0.9 (mg/dl), ICG R15:26.8 (%), PT: > 100%, AFP:33 (ng/ml), HCV-Ab:(-), HBs-Ag:(-). Hepatic angiogram showed a 20 cm sized tumor in the left lobe and many large and small tumors in the right lobe. He received chemoembolization (TAE) five times during seven months. At the time of the fifth hepatic angiogram, TAE was assessed as ineffective because of the resulting collateral feeding arteries. Thus, he underwent left lobectomy, partial resection of the right lobe, and partial "Wrapping therapy" for the regions including foci supplied with parasitic branch. Afterwards, he had TAE two times. One year and five months after the procedure, he is still alive without signs of recurrence.

Aged↗

[A case of successful management of advanced cholangiocellular carcinoma by repeated hepatic resection].

A 50-year-old woman with advanced cholangiocellular carcinoma (CCC) underwent extended left hepatectomy and catheterization into the hepatic artery. Following the procedure, intra-arterial infusion chemotherapy of the fluorouracil (5-FU) was performed. This chemotherapy was given 13 times at 2,500 mg for 10 months, so the total dose of 5-FU was 32.5 g. About two years after the operation, the patient underwent hepatic resection again for solitary recurrence of CCC. The prognosis of CCC is very poor. Aggressive surgical resection may be the only method to assure a good outcome. However, the survival rate after curative resection has been low. Adjuvant hepatic arterial infusion chemotherapy after surgery may be effective for a good prognosis.

Antimetabolites, Antineoplastic↗

[A case of non-resectable pancreatic cancer surviving more than 4 years by intra-arterial infusion chemotherapy with angiotensin-II].

This is a report of a 62-year-old woman whose non-resectable pancreatic cancer had been treated effectively by a new method of intra-arterial regional chemotherapy for more than 4 years. A catheter was placed into the celiac artery during laparotomy, and an intra -arterial chemotherapy (methotrexate (50 mg) and Angiotensin-II (AT-II, 5 micrograms)) has been repeated every other week (108 times) in addition to the external beam therapy (50 Gy). Both pain relief and "partial response" in the size of tumor have been obtained, with no hepatic metastasis or adverse effect. She died of brain metastasis at 51 postoperative months. Autopsy revealed that the pancreatic tumor was mostly replaced by fibrous connective tissues. Scintigraphic study indicated that the intra-arterial infusion of AT-II increased the blood flow in the tumor but decreased it in the surrounding non-cancerous tissues. This seemed to explain the effective loco-regional control in the present case.

Angiotensin II↗

Nitric oxide, a physiological modulator of mitochondrial function.

The effect of nitric oxide (NO) on the energy transfer reactions of mitochondria was examined under different oxygen tensions. Mitochondrial functions, such as respiration, ATP synthesis and regulation of membrane potential, were inhibited by NO in a concentration-dependent manner. In the presence of various substrates, NO also inhibited uncoupled respiration in an oxygen concentration-dependent manner. The inhibited function recovered completely at certain times after adding NO. When added to mitochondrial suspensions, NO disappeared rapidly from the medium and more rapidly at high oxygen tensions than at low oxygen tensions as determined by the formation of methemoglobin and EPR methods. From these results it is concluded that NO might play an important role in the regulation of mitochondrial functions particularly under low oxygen concentrations.

Animals↗

[Adult pneumococcal meningitis complicated by cerebral infarction: a case report].

We describe a 36-year-old man with pneumococcal meningitis who suddenly showed a left central type facial palsy and left hemiparesis. Magnetic resonance imaging (MRI) revealed a low intensity area in the posterior limb and genu of the right internal capsule to caudate nucleus in T1-weighted images and a high intensity area in T2-weighted images. We surmised vasculitis as the cause of cerebral infarction, because steroid treatment was effective.

Adult↗

[Recombinant virus-mediated transfer of the wild-type p53 gene is a potent therapeutic strategy for human cancer].

Tumor suppressor p53 gene, which is most commonly mutated in human cancers, plays an important role in the control of cell cycle and the induction of apoptosis (programmed cell death). Transfection of the wild-type p53 gene into tumor cells induced either growth suppression or apoptosis. We have examined the effect of the recombinant retroviral or adenoviral vector expressing the wild-type p53 gene on the tumor cell proliferation as well as on the sensitivity of infected-tumor cells to various anticancer agents. The possible application of recombinant virus-mediated direct in vivo transfer of the wild-type p53 gene to human cancer therapy will be discussed.

Adenoviridae↗

Inhibition of neutrophil superoxide generation by hypericin, an antiretroviral agent.

We previously reported that phorbol 12-myristate 13-acetate (PMA)-induced superoxide (O2.-) generation of neutrophils was inhibited by hypericin, a photosensitizing pigment found in St. Johnswort (herb Hypericin triquetrifolium Turra), via a mechanism involving protein kinase C (PKC). To obtain further insights into the mechanism of inhibition, the effects of hypericin on stimulation-dependent O2.- generation and related enzymes of neutrophils were investigated. Hypericin inhibited O2.- generation of neutrophils induced by PKC-dependent and -independent stimuli in a light- and concentration-dependent manner. Oxygen was required for the light-dependent inhibition by hypericin. NADPH oxidase activity in a cell-free system and TNF-alpha-induced tyrosyl phosphorylation of neutrophil proteins were also inhibited by hypericin in a concentration- and light-dependent manner. However, tyrosine kinase of p60src, an enzyme not bound to a membrane, was not inhibited either in the light or in the dark. Oxygen uptake of neutrophils by photosensitization with hypericin resulted in the formation of singlet oxygen (1O2), O2.-, and hydroxyl radical (.OH) and enhanced lipid peroxidation. The formation of 1O2 was inhibited by azide, a quencher of 1O2, but not by desferrioxamine (DSF), a ferric ion chelator. By contrast, both generation of .OH and lipid peroxidation were inhibited by DSF but not by azide. Furthermore, PMA-induced O2.- generation inhibited by hypericin partially recovered in the presence of azide but not DSF. These results suggested that the light-dependent inhibition of O2.- generation by hypericin might be due to inhibition of tyrosine kinase, PKC, and NADPH oxidase via an oxygen-dependent mechanism, possibly through both Type I and II photosensitization mechanisms.

Anthracenes↗