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Biomedical subjects

T Ikenaga

Publications and source records attributed to T Ikenaga.

At least 19 recordsLinked to original sources

Penicillin derivatives induce chemical structure-dependent root development, and application for plant transformation.

We investigated five penicillin derivatives that are popularly used for transformation experiments with Agrobacterium rhizogenes-penicillin G, carbenicillin, ampicillin, amoxicillin and cephalexin-for their effects on the growth and morphology of Beta vulgaris, Capsicum annuum and Glehnia littoralis roots. Attention was given to the relationship between their chemical structures and functions. Ampicillin was found to stimulate root elongation but inhibit root branching, whereas carbenicillin inhibited root elongation but promoted root branching. Root cultures were also exposed to hydrolyzed products of these antibiotics-i.e. phenylmalonic acid (PM), phenylglycine and 6-aminopenicillanic acid (6-APA): PM inhibited root elongation the most, while root elongation was supported best by 6-APA. These results indicate that both the side chains and the major component of penicillin derivatives affect root development and that the nature of the side chains is responsible for the responses. Ampicillin but not carbenicillin was used in subsequent experiments described herein to eliminate bacteria and to support root growth of transformants of the recalcitrant plants.

Amoxicillin↗

Effects of intravascular perfusion of cooled crystalloid solution on cold-induced brain injury using an extracorporeal cooling-filtration system.

BACKGROUND: We evaluated cerebral metabolic change during brain hypothermia with intravascular perfusion of cooled crystalloid solution using an extracorporeal cooling-filtration system and cerebroprotective effects of this hypothermia on brain injury in an animal model. METHOD: Microdialysis probes were implanted into the bilateral parietal cortices. A cold-induced brain injury was produced behind the microdialysis probe on the right parietal cortex. Immediately after injury in the cooled group (n=9), Ringer's solution cooled to 5 degrees C was infused into the right vertebral artery after occlusion of the bilateral common carotid and the left vertebral arteries. Excessive fluid was ultrafiltrated by a dialyzer. Brain temperature was maintained at about 20 degrees C for 60 minutes. In 7 dogs, three neck arteries were occluded for 60 minutes after injury without cooled fluid infusion. The extracellular concentrations of glutamate, lactate, and pyruvate were measured serially for 180 minutes after injury. FINDINGS: Extracellular glutamate concentrations in the cooled group did not increase, while there was a significant increase in the injured hemisphere as compared to the uninjured hemisphere in the non-cooled group ( P<0.05). Extracellular lactate concentrations increased slightly after occlusion in both groups. The depth of cortical injury was limited in the cooled group, but extended into the white matter in the non-cooled group up to 240 minutes after injury. INTERPRETATION: Occlusion of three main arteries induced ischaemia under critical threshold in canine brains. Under this condition, intravascular cooling with crystalloid solution suppressed accumulation of extracellular glutamate and reduced tissue damage in the early phase after cold-induced brain injury, as cerebroprotective effects. This information suggests that a method employing brain hypothermia via intra-arterial cooling with an extracorporeal cooling-filtration system has potential to achieve successful, safe, selective brain cooling.

Animals↗

Expression and characterization of human rheumatoid factor single-chain Fv.

The variable region of heavy chain [V(H)] of human rheumatoid factor (hRF) IgM was connected with the variable region of light chain [V(L)] with the peptide-linker (GGGSGGGSGGGS) by genetic engineering method and the single-chain Fv (scFv) was expressed in E. coli. On design, scFv and scFv (tag) were planned; the latter had a detection marker at the carboxyl-terminal. These scFvs were expressed as inclusion bodies in E. coli, purified in the presence of 8 M urea by gel filtration and renatured to the active form in vitro. As a control, the Fv, non-covalently associated V(H) and V(L) fragments, was also constructed. The 3 derivatives showed almost the same binding activity to rabbit-IgG to which hRF is cross-reactive. ScFv (tag) was the most stable against urea among the 3 derivatives.

Amino Acid Sequence↗

Induction of furanocoumarin biosynthesis in Glehnia littoralis cell suspension cultures by elicitor treatment.

Cell suspension cultures were established from Glehnia littoralis plants belonging to two different geographic strains. When the cells were treated with yeast extract, they started to produce and excrete furanocoumarins into the culture medium; a major component, bergapten, and a minor one, xanthotoxin, were detected and identified by HPLC and GC/MS. Changes in phenylalanine ammonia-lyase (PAL) activity and furanocoumarin production after elicitor treatment were traced, showing that PAL activity increased rapidly, reached a maximum after 24 h, and then declined to the normal level after 96 h which preceded the induced bergapten production. The induced-PAL activity of the cultured cells established from an S-type plant which accumulated trace amounts of furanocoumarins was about 50% of that in the cultured cells from an N-type plant that accumulated more than 0.1% furanocoumarins in the underground parts. However, the elicited production of bergapten was about six times higher in the cell cultures from the S-type plant. Addition of the PAL inhibitor 2-aminoindan-2-phosphoric acid (AIP) at 10 microM suppressed the induction of PAL activity and furanocoumarin production.

5-Methoxypsoralen↗

Anthocyanin production of Glehnia littoralis callus cultures.

A stable callus line that produces anthocyanins was established from callus derived from a petiole of a Glehnia littoralis seedling and subcultured in the dark. The major anthocyanin which made up about 60% of the total anthocyanins was determined as cyanidin 3-O-(6-O-(6-O-(E)-feruloyl-beta-D-glucopyranosyl) -2-O-beta-D-xylopyranosyl-beta-D-glucopyranoside) by chemical and spectroscopic analyses. Anthocyanin contents in the cells cultured on B5 basal medium containing NAA (1 mg l-1), kinetin (0.01 mg l-1) and 3% sucrose reached 14% (dry wt basis) and the productivity has been sustained for 5 years.

Anthocyanins↗

[Unilateral dissection of the cervical portion of the internal carotid artery and ipsilateral multiple cerebral infarctions caused by suicidal hanging: a case report].

This paper presents a case of traumatic dissection of the unilateral internal carotid artery of the cervical portion caused by hanging. A 63-year-old man attempted suicide by hanging and was rescued immediately after. No neurological deficits were detected for the first 4 hours. But then, right hemiplegia, aphasia and disturbed consciousness suddenly developed. On the 2nd day, MRI revealed multiple infarctions in the left cerebral hemisphere. MR angiography demonstrated severe stenosis at the cervical portion of the left internal carotid artery due to dissection. The left middle cerebral artery was not demonstrated. The patient was conservatively treated with fibrinolytic agents and regained consciousness gradually. But aphasia and right hemiplegia remained. During the next few weeks, the stenosis at the ICA slightly improved and the MCA was completely recanalized. Extracranial Doppler sonography revealed chronological hemodynamic changes of mean flow velocity and pulsatility index at the proximal and distal portion of the ICA stenosis.

Carotid Artery Diseases↗

Production of choleretic substances in the capitulum, leaf and stem of Artemisia capillaris during the plant growth cycle.

Five Artemisia capillaris plants were selected at random from among a bed of twenty plants cultivated in a field for one year. Several branches were collected from each plant once a month, except in August and October, when two collections were made during budding and flowering. Each organ (leaf, stem, and capitulum) was separated from the branch and dried, and later analyzed for capillarisin and 6,7-dimethylesculetin content by high-performance liquid chromatography (HPLC). The capillarisin and 6,7-dimethylesculetin content reached maximum levels in the leaf just before the appearance of flower buds at end of July. About one month later, at the end of August during budding and flowering, capillarisin content in the capitulum reached a peak and then decreased. On the other hand, 6,7-dimethylescuretin content reached a maximum at the beginning of September, two weeks after the capillarisin maximum. The results suggest that the most appropriate time to harvest A. capillaris for use as a crude drug is between the flower bud stage and early flower stage, from late August to early September.

Calibration↗

Renin inhibitors. III. Synthesis and structure-activity relationships of transition-state inhibitors containing dihydroxyethylene isostere at the P1-P1 site.

The design, synthesis and structure-activity relationships of transition-state inhibitors containing the dihydroxyethylene isostere at the scissile site are described. The compounds with (2S,3R,4S)-4-amino-5-cyclohexyl-1-morpholino-2,3-pentanediol at the P1-P1 site are potent renin inhibitors. (2S,3R,4S)-4-[N-[(2S)-3-Ethylsulfonyl-2-(1-naphthylmethyl)propiony l]-L- norleucyl]amino-5-cyclohexyl-1-morpholino-2,3-pentanediol (2) (BW-175), which is the most potent inhibitor (IC50: 3.3 nM against human renin) in this series, poorly inhibits cathepsin D (IC50: 26000 nM) and pepsin (IC50: > 100000 nM), and thus it is specific for renin. Compound 2 contains only one amino acid and showed an oral bioavailability of 2.8% at 10 mg/kg and 9.7% at 30 mg/kg in rats. The interaction between renin and inhibitor 2 is discussed on the basis of molecular modeling studies.

Animals↗

Branch retinal artery occlusion following thyroidectomy for papillary carcinoma of the thyroid: report of a case.

A rare case of branch retinal artery occlusion (BRAO) following a subtotal thyroidectomy for thyroid cancer in a 58-year-old woman is reported herein. Five days after her thyroidectomy, the patient complained of having had a reduction in visual acuity and visual field loss of the superior nasal side in her right eye since the operation. BRAO was diagnosed following the discovery by funduscopy of inferotemporal branch artery occlusion with retinal edema, hemorrhage, and periarterial sheathing in the right eye. Despite immediately puncturing the anterior camera and massaging the eyeball while administering intravenous anticoagulant therapy, the visual field disturbance remained unchanged. The most common causative factor of postoperative sudden BRAO is reported to be emboli. However, in our case, the most likely cause was the stretching and pressure exerted on the carotid artery with consequent atheromatous plaque formation at the time of thyroidectomy.

Carcinoma, Papillary↗

Restriction fragment length polymorphisms (RFLPs) of medicinal plants and crude drugs. I. RFLP probes allow clear identification of Duboisia interspecific hybrid genotypes in both fresh and dried tissues.

A simple and efficient method for identification of Duboisia leichhardtii F. Muell, D. myoporoides R. BR. and their interspecific hybrid was established by analyzing restriction fragment length polymorphism (RFLP) profiles using non-radioactive rice ribosomal DNA as a probe. This procedure was shown to be applicable to both fresh and dried samples, and also suitable for detection of somatic hybrid at the callus stage after protoplast fusion.

DNA↗

Phosphoramidon-sensitive endothelin-converting enzyme in the cytosol of cultured bovine endothelial cells.

Neutral metalloproteases with endothelin-1 (ET-1) converting activity were detected in membranous and cytosolic fractions of cultured endothelial cells (EC) from bovine carotid artery in a ratio of 5:1, respectively. The cytosolic enzyme specifically and quantitatively converts big ET-1 to ET-1 (Km = 10.7 microM), but does not convert big ET-3. Like the membranous enzyme, the cytosolic enzyme is only active at pH 6.5-7.5, and is competitively inhibited by phosphoramidon (Ki = 0.79 microM). The apparent molecular weight of the cytosolic enzyme is about 540 kD, which is 5-6 times greater than that of the membranous enzyme. These results indicate the presence of two types of phosphoramidon-sensitive neutral ET-converting enzyme in vascular EC.

Animals↗

In vivo effect of human granulocyte colony-stimulating factor derivatives on hematopoiesis in primates.

Using cynomolgus monkeys, we studied the hematopoietic effect and antigenicity of the human granulocyte colony-stimulating factor (hG-CSF) derivatives mutated at N-terminal amino acids (NC-59 and KW-2228) and that lacking N-terminal amino acids (M-7) in comparison with intact hG-CSF. These compounds were subcutaneously administered daily into the back of cynomolgus monkeys at the doses of 1 and 100 micrograms/kg for 2 weeks, and withdrawn for 2 weeks (1st course). After that, the same schedule was repeated (2nd course), and intact hG-CSF and KW-2228 were further administered for 2 weeks (3rd course). In the first course, all of the G-CSF derivatives showed excellent dose-dependent granulopoietic activities. In the 2nd course, however, the activities of NC-59 and M-7 were decreased and the elevations of binding and neutralizing antibody titers were observed. On the other hand, KW-2228 showed granulopoietic activities equal to or better than that of intact hG-CSF and had low antibody titer throughout all the courses.

Amino Acid Sequence↗

Flat adenoma and flat mucosal carcinoma (IIb type)--a new precursor of colorectal carcinoma? Report of two cases.

Two flat adenomas and a flat mucosal carcinoma of the colon were reported in patients with synchronous and metachronous colonic carcinomas. These lesions were almost flat and were not detected by preoperative endoscopic examinations. Colonoscopists should be aware of the presence of flat adenomas, which can be easily missed, and recognize them as lesions that play an important role in the "adenoma-carcinoma sequence."

Adenoma↗

[A cooperative study of alternating immunochemotherapy with futraful and PSK (second report)--3-year survival rate].

Patients who had undergone gastrectomy for stomach cancer were placed on adjuvant chemotherapy two weeks after surgery. They were divided into three groups according to the following regimen in order to compare the 3-year survival rate : in the first group, administration of futraful was carried out for 3 consecutive months and followed by administration of PSK for 2 consecutive months. This course was repeated for more than 2 courses. Administration of futraful in the second group was repeated for 3 consecutive months with 2 months of withdrawal and repeated for more than 2 courses. The third group received surgery alone. When all the patients of each group were compared, there was no difference in 3-year survival rate, but the group receiving alternating therapy with futraful and PSK showed a significantly high survival rate for the first year only. Further, among patients having stage III carcinoma, those with n2 + n3 or poorly differentiated adenocarcinoma had a remarkably high survival rate.

Adjuvants, Immunologic↗

[Safety evaluation of micronomicin IV. Acute toxicity in rats, rabbits and dogs after drip intravenous infusion].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc, as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Toxicological studies of MCR were carried out for safety evaluation as follows: Studies were carried out to assess acute toxicity, when administered in 1 hour by drip intravenous infusion to Wistar rats, Japanese White rabbits and Beagle dogs. The results of the studies are summarised as follows: There was no difference on acute toxicity between drip intravenous infusion (d.i.v.) and intramuscular injection (i.m.) in rats. However, acute toxicity of d.i.v. was less than that of bolus intravenous administration (i.v.) in rats. Acute toxicity of d.i.v. was stronger than that of i.m. in dogs when administered in rats. Acute toxicity varied with species, and it was ranked in rabbits not equal to dogs greater than rats. There was no difference on symptoms between d.i.v. and i.m.

Aminoglycosides↗

[Safety evaluation of micronomicin VI. Subacute toxicity in rabbits after drip intravenous infusion].

Micronomicin (MCR) is a new aminoglycoside antibiotic produced by Micromonospora sagamiensis var. nonreducans which was isolated from soil collected at Sagamihara City by Nara et al. This antibiotic shows a close similarity to gentamicin C components in physical and chemical properties. The antibacterial activity of MCR is broad-spectrum and almost equal to that of gentamicin C complex. MCR exhibits particularly high activity against Pseudomonas, Proteus, Klebsiella pneumoniae, Serratia, etc. as well as against some Pseudomonas aeruginosa strains resistant to gentamicin C1a. Subacute toxicity studies of MCR in rabbits were carried out by drip intravenous infusion (d.i.v.) comparing with intramuscular injection (i.m.) for 30 days (doses; d.i.v. = 4, 25, 63 mg/kg, i.m. = 63 mg/kg). The results of the studies are as follows: Animals did not die at any dose. Renal disorders occurred mainly at the dose level of 63 mg/kg; they were almost similar to those observed when administered by i.m., and the grade of disorders in d.i.v. was the same as in i.m. The maximum safety dose was 4 mg/kg.

Aminoglycosides↗