Biomedical subjects

K Ushijima

Publications and source records attributed to K Ushijima.

At least 19 recordsLinked to original sources

PubMed1998

Site-specific cleavage of tRNA by imidazole and/or primary amine groups bound at the 5'-end of oligodeoxyribonucleotides.

Sequence specific RNA cleaving molecules were synthesized by attaching novel polyamine derivatives bearing imidazole and/or primary amine groups to the 5'-end of DNA oligonucleotides as the sequence-recognizing moieties. The actions of the molecules on a half-tRNA(Asp) were investigated. The oligonucleotides directed the nuclease activity (the imidazole and the primary amine are the catalytic groups) of the enzyme to the nucleotides directly adjacent to the complementary target sequence on the substrate RNA. The cleavage reaction shows a bell-shaped pH dependence with a maximum at pH 7.0, indicating the participation of protonated and non-protonated imidazoles residues in the process. The specificity of these hybrid enzymes can be easily altered, and they should prove to be useful tools for probing RNA structures in solution and as potential reactive groups in antisense oligonucleotide derivatives. We also describe the site-specific cleavage of tRNA(Asp) by the cleaving reagents bearing imidazole and/or primary amine groups at the 5'-end of oligodeoxyribonucleotides.

Amines↗

PubMed1998

Skin vasomotor reflex as an objective indicator to assess the level of regional anesthesia.

UNLABELLED: We examined whether the absence of a skin vasomotor reflex (SVmR), which represents a sympathetic vasoconstrictive response to various stimuli, is an objective indicator of a somatosensory blockade. Skin blood flow was measured by using a laser Doppler flowmeter on the index finger tip. The somatosensory blockade level was determined in 15 patients under subarachnoid anesthesia. A cold stimulus, an ice cube applied to the skin, was repeated sequentially at each dermatome from L3 cephalad. The uppermost dermatome with negative response (the SVmR cold level) was determined, and the SVmR pain level was determined similarly using an electrical impulse (20-mA, 50-Hz, 0.25-ms square wave). The SVmR cold level and the SVmR pain level showed significant correlation with the conventionally assessed cold level (r = 0.83) and the pinprick level (r = 0.96). We conclude that the SVmR is useful to objectively estimate the level of somatosensory block induced by regional anesthesia. IMPLICATIONS: We evaluated the absence of decrease in skin blood flow after various stimuli as an indicator of somatosensory blockade. In patients under subarachnoid anesthesia, the uppermost level with negative response showed significant correlation with the conventionally assessed blockade level. This method is useful for objective assessment of regional anesthesia level.

Adult↗

PubMed1998

Intestinal absorption of ursodeoxycholic acid in children and adolescents with inflammatory bowel disease.

BACKGROUND: Ursodeoxycholic acid absorption in the proximal intestine may be impaired in patients with inflammatory bowel disease. METHODS: We examined the intestinal absorption of ursodeoxycholic acid by the oral ursodeoxycholic acid tolerance test in 19 children and adolescents with inflammatory bowel disease at various stages, including 8 patients with unoperated Crohn's disease, 3 patients with ileal-resected Crohn's disease, 8 with ulcerative colitis, and 8 healthy control subjects. RESULTS: Ursodeoxycholic acid malabsorption was present in all patients with unoperated Crohn's disease in the first diagnosed active stage, in 3 of 5 patients in a relapsing active stage, and in 2 of 8 patients in remission. Ursodeoxycholic acid absorption was significantly lower in patients in the first diagnosed active stage than in the healthy controls (p < 0.01) or in patients in remission (p < 0.01). There was no significant difference between healthy controls and the patients in a relapsing active stage or in remission. Ursodeoxycholic acid absorption was abnormal during the first postoperative month in patients with ileal-resected Crohn's disease, but normalized over time. Malabsorption of ursodeoxycholic acid was not observed in any patients with ulcerative colitis. CONCLUSIONS: These findings suggest that absorption of ursodeoxycholic acid in the proximal intestine is impaired in patients with Crohn's disease and that the oral ursodeoxycholic acid tolerance test is a convenient and useful means of evaluating the absorption of bile acid in the proximal intestine in pediatric patients with ileal or ileocolic Crohn's disease.

Adolescent↗

PubMed1998

[The majority of emergency calls are erroneous].

An emergency call system has been used to summon specialists for cardiopulmonary resuscitation in Kumamoto University Hospital since 1986. Many improvements have been made to the system since it was established. We performed a prospective evaluation of calls made during the period from April 1, 1996 to March 31, 1997. There were a total of 36 calls, but only two of them were judged to be true emergencies. While at first we considered the number of calls reflected a growing awareness of the cardiopulmonary resuscitation team in the hospital, the large number of erroneous calls (94%) indicated other factors needed to be considered. Further investigation revealed the existence of a special, and little-known, telecommunication system connecting various administrative offices of the Japanese Government. Some of the phone numbers in this system are similar to the emergency call number. Thus many of the emergency calls were probably caused by administrative officers who misdialed. We are proposing to change this emergency call number.

Cardiopulmonary Resuscitation↗

PubMed1997

Optimal timing of a second-look operation for advanced epithelial ovarian cancer.

To clarify the optimal timing of second look operation (SLO) for advanced ovarian cancer, we retrospectively reviewed the records of 53 patients with FIGO stage 2, 3 and 4 epithelial ovarian cancer. SLOs were performed more than 12 months after primary surgery in 35 patients (late SLOs), and immediately after first-line chemotherapy in 18 patients (early SLOs). We examined data on SLO findings and patients' clinical courses. SLO findings were positive 5 (27.7%) of 18 in the early SLO group and in 11 (31.4%) of 35 in late SLO group. Positive findings were detected by washing cytology in 3 (60%) of the 5 in the early SLO group compared with 2 (18.2%) of the 11 in the late SLO group. Patients with microscopic disease had better prognosis than patients with macro lesions. False-negative SLO findings were 30.8% in the early SLO group and 12.5% in the late SLO group. All patients who recurred after negative SLOs had grade 2 and 3 tumors. The benefits of SLO were limited to accurate evaluation of first-line chemotherapy and early detection of persistent disease. In these implications, early performance of SLO is recommended.

Adult↗

PubMed1997

[An anesthesia machine malfunction due to dew condensation produced by abnormally high humidity in the electronically-controlled panel].

We present a case of anesthesia machine (NAR-KOMED 2CTM; N2C) malfunction caused by dew condensation. N2C is electronically controlled by an alarm-panel using the remote display. Abnormally high humidity in the operating room made dew condensation in the alarm-panel resulting in an electronic short circuit. Of great importance may be the damp proof improvement on medical equipment including anesthesia machines which have electronic circuits.

Anesthesiology↗

PubMed1997

[General anesthesia for an infant with Rubinstein-Taybi syndrome].

A 5-year-old girl with Rubinstein-Taybi syndrome (RTS) was scheduled for ophthalmic surgery under general anesthesia. RTS is a well-defined syndrome with facial abnormalities including a high palate and micrognathia, broad thumbs and big toes, and mental retardation as main clinical features, which may be complicated with repeated respiratory infections, cardiac anomalies, and so on. Anesthesia was uneventfully induced and maintained with the inhalation of oxygen, nitrous oxide and sevoflurane. Special attention was paid to the possibilities of the difficult airway, aspiration pneumonia and cardiovascular dysfunction during anesthesia. No complications were observed throughout the perioperative procedures.

Anesthesia, General↗

PubMed1997

[Propofol anesthesia for a schizophrenic patient].

A 41-year-old man weighing 68 kg was scheduled for bilateral tonsillectomy because of palmoplantar pustulosis. The patient had been diagnosed as schizophrenic 10 years earlier. Psychotropic agents, mosapramine (75 mg.day-1), bromperidol (6 mg.day-1), cloxazolam (3 mg.day-1), biperiden (1 mg.day-1) and nitrazepam (5 mg as needed), were administered until the day before surgery. On the day of surgery, atropine (0.g mg) and midazolam (4 mg) were administered intramuscularly as premedication. Anesthesia was induced by intravenous propofol (120 mg) and fentanyl (100 microgram) followed by nasotracheal intubation using vecuronium (7 mg). Anesthesia was maintained with inhalation of oxygen and nitrous oxide (2 l.min-1 each) and the intravenous infusion of propofol (5-10 mg.kg-1 x h-1) supplemented by fentanyl (100 microgram). The patient recovered from anesthesia uneventfully. Immediately after surgery, intravenous haloperidol (5 mg) and intramuscular biperiden (1 mg) were given. The daily oral administration of psychotropics was resumed on the first postoperative day. There were no complications such as hypotension, arrhythmia, or worsening of the mental condition, throughout the course.

Adult↗

PubMed1997

[Promising new drugs for gynecological cancer].

Five promising new drugs for gynecological cancer were reviewed. Taxans (Paclitaxel: Taxol and Docetaxel: Taxotere) diterpenoid plant products enhance the polymerization of tublin. Taxol showed significant activity for platinum refractory ovarian cancer in a phase 1 clinical trial in the United States. The combination with cisplatin (CDDP) showed superior results to CDDP plus Cyclophosphamide and has been recognized as a new standard in adjuvant chemotherapy for advanced ovarian cancer. The major toxicities are myelosuppression, alopecia, and hypersensitivity reactions (HSRs). HSRs were overcome by pretreatment with anti-histamines and over 24 hours administration. It was also reported that Taxol was administered safely by over 3 hours infusion with reduced myelotoxicity, but the incidence of HSRs may be increased. Clinical trials of intraperitoneal administration and combination with Carboplatin (CBDCA) are ongoing. Taxotere, an analog of Taxol, is also effective as Taxol with a low incidence of HSRs. Topoisomerase inhibitors (Irinotecan hydrochloride: CPT-11 and Topotecan) have promising antitumor activity for ovarian and cervical cancer. CPT-11 is a semisynthetic camptothesin analog developed in Japan. It was also effective for platinum-resistant ovarian cancer, such as mucinous and clear cell carcinoma. An adverse effect was observed in the combination of CPT-11 and CDDP. The phase 1 clinical trial showed a 40% response rate against recurrent ovarian cancer. CPT-11 50-60 mg/m2 (day 1,8,15) and CDDP 50-60 mg/m2 (day 1) are a recommended schedule. The major toxicities are neutropenia and diarrhea. Thrombocytopenia is not severe and diarrhea is also controllable. Topotecan is also a promising topoisomerase inhibitor and reported superior result to Taxol for platinum refractory ovarian cancer. A phase II trial is ongoing for ovarian and cervical cancer in Japan. Nedaplatin, a new analog of cisplatin, has similar activity especially for cervical cancer with less myelotoxicity and nephrotoxicity.

Antineoplastic Agents, Phytogenic↗

PubMed1996

Hairpin antisense oligonucleotides containing 2'-methoxynucleosides with base-pairing in the stem region at the 3'-end: penetration, localization, and Anti-HIV activity.

Hairpin antisense oligodeoxyribonucleotides containing 2'-methoxynucleosides were more active in the micromolar concentration range than linear and DNA hairpin phosphorothioate oligonucleotides with the same sequence. Furthermore, the abilities of hairpin antisense and random hairpin phosphorothioate oligonucleotides to inhibit HIV-1 replication were examined. Antisense oligonucleotides inhibit the replication and the expression of HIV-1 more efficiently than random-oligomers of the same length or with the same internucleotide modification. Four different target sites (gag, pol, rev, and tat) within the HIV-1 genome were studied with regard to the inhibition of HIV-1 replication by antisense oligonucleotides. Antisense oligomers complementary to the sites of the initiation sequences of gag were most effective. The [32P]-labeled hairpin phosphorothioate oligonucleotide was rapidly assimilated by MOLT-4 cells, whereas the [32P]-labeled hairpin phosphodiester oligonucleotide was not. In MOLT-4 cells treated with the FITC-hairpin phosphorothioate oligonucleotide containing 2'-methoxynucleosides by a confocal laser scanning microscope, diffuse fluorescence was observed in the cytoplasm. Interestingly, fluorescent signals accumulated in the nuclear region of chronically infected MOLT-4/HIV-1 cells after a 60 min incubation.

Antiviral Agents↗

PubMed1996

Nonenzymatic sequence-specific cleavage of duplex DNA via triple-helix formation by homopyrimidine phosphorothioate oligonucleotides.

Phenanthroline was attached covalently to the 5'-terminus of the unmodified and modified (3'-terminal phosphorothioate) oligonucleotide sequences, TTTTTTCTTCTCTTTCC (OP-17 mer) and TTTTTTTCTTCTCTTTCsC (OPRp-17 mer or OPSp-17 mer) via a phosphoramidite bond. Simian virus 40 DNA contains a single target site for these oligonucleotides. In the presence of copper ions, the efficient double-stranded cleavage at 37 degrees C and pH 7.0 was observed by agarose gel electrophoresis. The asymmetric distribution of the cleavage sites on the two strands revealed that the cleavage reaction took place in the minor groove, even though the linker was located in the major groove. Of particular interest are the 3'-terminal phosphorothioate oligonucleotide-phenanthroline derivatives (Rp or Sp), which were found to have cleavage activities of the same order as for the oligonucleotide phenanthroline (OP-17 mer). Furthermore, the OPSp-17 mer was intact after incubation in 10% fetal bovine serum for 24 h, whereas, the OPRp-17 mer was slightly more unstable than the OPSp-17 mer. However, the OP-17 mer was completely degraded. An increased resistance to nucleases has been observed by the introduction of phosphorothioate groups on the 3'-terminus of oligonucleotide-phenanthroline derivatives. This stabilization should help us to design much more efficient chemical recognition enzymes and antisense nucleic acid based anti-viral therapies, which could be used as tools in cellular biology.

Animals↗

PubMed1996

Improvement of intraperitoneal chemotherapy for rat ovarian cancer using cisplatin-containing microspheres.

Microspheres consisting of L-lactic acid and glycolic acid copolymer containing cisplatin (CDDP-PLGA) were developed to improve the delivery of cisplatin. We evaluated the effects of intraperitoneal administration of cisplatin prepared as CDDP-PLGA in rats with ovarian cancer. The toxicity, platinum distribution, and therapeutic effects of CDDP-PLGA were evaluated as compared with those in the case of cisplatin aqueous solution. The LD50 of CDDP-PLGA was almost four-fold higher than that of cisplatin aqueous solution. CDDP-PLGA released cisplatin slowly and achieved a higher concentration in the peritoneal cavity and in peritoneal tumors for prolonged periods, while the tissue concentration of cisplatin was reduced elsewhere in the body, as compared with the case of cisplatin aqueous solution. The survival of rats with peritoneal carcinomatosis was increased by this delivery system relative to cisplatin aqueous solution. CDDP-PLGA thus allows a higher dose to be given without increasing systemic toxicity, enhancing the therapeutic effect of cisplatin.

Animals↗

PubMed1996

Reassessment of second look operation for epithelial ovarian cancer.

We retrospectively reviewed 91 patients with epithelial ovarian cancer who underwent second-look operation (SLO). SLO identified a persistent tumor in 18 (19.8%) of 91 patients. Of these 18 patients, 13 (72.2%) showed disease progression after SLO. Patients with a positive SLO in which the identification of the persistent disease was only possible by washing cytological study showed better prognosis than patients with macroscopic lesions. Of the 73 patients with a negative SLO, 12 (16.4%) developed recurrence after cessation of treatment. These 12 patients were from stage 1c to 3 with Grade 2 and 3 tumors. The SLO findings were more sensitive than the serum tumor marker in identifying persistent disease. Also we reviewed 55 patients having no SLO. Among 57 cases in stage 1 and 2 with Grade 1 tumor, there were no cases of recurrence, regardless of whether they had SLO or not. Our results suggest that SLO findings correlate well with the patient's prognosis. SLO may not be needed for patients in stage 1 and 2 with Grade 1 tumor. Patients with advanced stage disease with Grade 2 and 3 tumors have high-risk for recurrence after negative SLO. While SLO is still of benefit in management of ovarian cancer, refinements are needed to determine its indication and scheduling.

Adult↗

PubMed1996

Experimental intraperitoneal administration of cisplatin-activated carbon for rat ovarian adenocarcinomas.

Selective delivery of a high level of cisplatin (CDDP) to the omentum, intraperitoneal disseminated tumors and lymph nodes was studied using a dosage form of CDDP-activated carbon. Although intraperitoneal CDDP-activated carbon delivered much higher levels of CDDP to the omentum, tumors and lymph nodes, a primary burst phenomenon of CDDP occurred just after administration. This indicates that activated carbon is an unsuitable particle to provide a slow steady release of CDDP.

Adenocarcinoma↗

PubMed1996

[Combination of irinotecan hydrochloride (CPT-11) and cisplatin as a new regimen for patients with advanced ovarian cancer].

It has been reported that the antitumor effect of CPT-11 is manifested through the inhibition of topoisomerase I by SN-38 which is an active metabolite of CPT-11 produced by intracellular carboxylesterase, and that CPT-11 is effective against recurrent ovarian carcinoma. We investigated the antitumor effect and adverse reactions in the combined therapy with CPT-11 and CDDP in patients with prior chemotherapy for recurrent carcinoma, and in 7 patients without prior chemotherapy, consisting of 4 patients with postoperative adjuvant chemotherapy for clear cell carcinoma and 3 patients with metastatic ovarian carcinoma. CDDP was administered on day 1 and CPT-11 was administered three times on days 1, 8 and 15. The dose of both CDDP and CPT-11 was 50 mg/m2 or 60 mg/m2. Adverse reactions were investigated in all patients and the antitumor effect was assessed in 12 patients with recurrent carcinoma who had measurable lesions. (1) The DLF was neutropenia. The neutrophil count nadiar occurred on day 18 or 19. Grade 3 or 4 adverse reactions were observed in 60% or more of the patients, but they disappeared following short term administration of G-CSF. In patients with recurrent carcinoma given CDDP and CPT-11 at 60 mg/m2, the incidence of grade 3 or 4 adverse reactions and number of occasions on which CPT-11 administration had to be postponed were higher than those in patients given 50 mg/m2. (2) Mild platelet reduction was observed. (3) Grade 3 or 4 diarrhea was observed in 3.2% of patients with recurrent carcinoma and in 7.7% of patients with metastatic ovarian carcinoma. (4) The antitumor effect was evaluated in 12 patients with recurrent carcinoma: CR in 2 patients. PR in 3, NC in 6, and PD in one. The response rate was 41.7%. (5) An antitumor effect was observed in 2 patients with serous carcinoma and in one patient each with mucous carcinoma, clear cell carcinoma and endometrial carcinoma. In conclusion, adverse reactions caused by the combination therapy with CPT-11 and CDDP (CPT-11: 50-60 mg/m2 on days 1, 8 and 15, CDDP: 50-60 mg/m2 on day 1) can be relieved by short term administration of G-CSF and it is suggested that the combination therapy may be effective in treating ovarian carcinoma.

Adult↗

PubMed1996

[Intraoperative use of plasma-derived activated factor VII (F VII a) in a hemophilia A patient with inhibitors].

We treated a 1-year 9-month-old boy with severe hemophilia A who developed high level of F VIII inhibitor. A placement of an implantable intravenous access device was scheduled under general anesthesia. After a slow induction using oxygen, nitrous oxide and sevoflurane, a peripheral venous line was placed and plasma-derived F VII a was infused. A catheter was inserted via the jugular vein to the SVC and it was connected to the device placed subcutaneously in his right chest wall. The peroperative blood loss was slight, and anesthesia and surgery went uneventfully.

Anesthesia, General↗

PubMed1995

Carbohydrate malabsorption.

Carbohydrate malabsorption is a very important clinical entity, particularly in pediatrics, where, if untreated, it can lead to malnutrition and failure to thrive. Malabsorption that can be treated readily with elimination of the offending carbohydrate. Knowledge by the physician of the specific mechanisms involved in the physiology of carbohydrate absorption and digestion will help in the handling of the clinical situation of malabsorption.

Carbohydrate Metabolism↗

PubMed1995

Absorption of fructose by isolated small intestine of rats is via a specific saturable carrier in the absence of glucose and by the disaccharidase-related transport system in the presence of glucose.

Previous studies have shown that the absorption of fructose is aided by simultaneous ingestion of glucose. The aim of the present study was to reproduce this finding in vitro to better understand the mechanism of the effect of glucose on absorption of fructose. The phenomena could not be reproduced with everted sleeves of rat intestine or brush border vesicles. In a perfused segment of isolated intestine, it was possible to demonstrate that the transport of fructose was accelerated when glucose was present in the perfusion medium. The enhanced transport was inhibited by sucrose and also by acarbazone, an inhibitor of intestinal alpha-disaccharidases. Phlorizin had no effect on the transport of fructose. The results of these studies indicate that there is a specific carrier for fructose saturated with a low concentration of the sugar, and that in the presence of glucose there is joint absorption of the two sugars by the disaccharidase-related transport system.

Animals↗