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Biomedical subjects

K Akatsuka

Publications and source records attributed to K Akatsuka.

At least 19 recordsLinked to original sources

Voltammetric detection of lectin using sugar labeled with electroactive substance.

The voltammetric detection of soybean agglutinin (SBA) was investigated on the basis of an interaction between the lectin and a sugar. Because galactose and lactose combined with SBA, the sugars were labeled by a Schiff base with an electroactive daunomycin. After the labeled sugar and SBA were mixed, measurements were carried out by voltammetry. When SBA-sugar binding occurs, a part of daunomycin of the labeled sugar is taken to the binding sites. As a result, SBA is detected by a change in the peak current of daunomycin, and the SBA-sugar interaction is evaluated. The length of the alkyl chain between daunomycin and the sugar was also considered. The electrode response to the concentration of SBA was linear over the range of 0.04-0.8 microg min(-1). The merits of this procedure are the convenient preparation of labeled sugar and a rapid measurement without separation. On the other hand, the detection of sugar at the 10(-9) mol dm(-3) level was achieved by a competitive reaction to limited binding sites of the lectin between the sugar and the labeled sugar.

Carbohydrates↗

[Clinical effects of cefoselis (CFSL) on infections in obstetric and gynecologic field and prevention of postoperative infections].

Clinical effects of cefoselis (CFSL) on various infections and prevention of postoperative infections in the field of obstetrics and gynecology were investigated with a total of 100 patients of 8 facilities in Yamagata and the following results were obtained: 1. For the patients (n = 70) who received the treatment with CFSL at 2 g/day for 5 days to prevent postoperative infections, the treatment was effective for such infections in 68 of 69 (98.6%) except one to whom the treatment was discontinued during the course. 2. For the patients with infections (n = 30) who were treated with CFSL at 2-4 g/day for 5-7 days, the treatment was markedly effective in 8/30 (26.7%), effective in 21/30 (70%) and not effective in 1/30 (3.3%). The overall rate of efficacy was 29/30 (96.7%). Based on the clinical effects for each isolate, the bacteriological efficacy was evaluated as 29/29 and the rate of bacterial eradication for each isolate was 23/29 (79.3%). 3. Laboratory test revealed liver functional abnormalities in one patient and eruption, a subjective/objective symptom caused by CFSL was noted in two patients. These results suggest that CFSL is effective for various infections in obstetric and gynecologic field and also the prevention of postoperative infections.

Adult↗

[Clinical studies of faropenem in the field of obstetrics and gynecology].

The clinical effect of faropenem was evaluated in 165 ambulatory patients with various infections in the field of obstetrics and gynecology at 10 institutions in Yamagata Prefecture. The results obtained are summarized below. 1. The rate of efficacy, as determined from the clinical effect following 3- to 7-day repeated administration at a dose of 600 mg/day, was 97.9% (46/47) for intrauterine infections, 92.0% (23/25) for adnexitis, 93.8% (15/16) for external genital infections, 88.9% (8/9) for mastitis, 94.0% (63/67) for cystitis, and 100% (1/1) for cervicitis. The overall efficacy rate was estimated to be 94.5% (156/165). 2. The rate of clinical efficacy, as classified by isolate, was high, 95.1% for Gram-positive bacteria, 100% for Gram-negative bacteria, and 100% for anaerobes. As for bacteriological response classified by isolate, the eradication rate was high, 91.4% (74/81) for Gram-positive bacteria, 98.4% (62/63) for Gram-negative bacteria, 89.5% (17/19) for anaerobes, and 93.9% (153/163) in all. 3. No adverse reactions or laboratory abnormalities were observed in any patient. The results presented suggest that faropenem is a highly safe and effective antibiotic for the treatment of obstetric or gynecological infections of various kinds in an ambulatory setting.

Adult↗

Rat zona pellucida glycoproteins: molecular cloning and characterization of the three major components.

The zona pellucida (ZP), the extracellular glycocalyx that surrounds the oocyte, is well known to mediate homologous gamete interaction. In a previous study from our laboratories, we reported the qualitative characterization of the rat ZP. The ZP in this species, like the mouse, hamster, and human, was found to contain three glycoproteins, namely rZP1, rZP2, and rZP3 (Araki et al. [1992] Biol Reprod 46:912-919). In this study, cDNAs encoding whole rat ZP major components have been isolated and characterized. A rat ovary cDNA library was screened with the mouse ZP3 and ZP2 cDNA probes, respectively. For rZP1 cDNA cloning, cDNAs generated using reverse transcriptase-polymerase chain reaction and rapid amplification of 5' and 3' cDNA ends, were isolated and sequenced. The rZP3 cDNA showed 1338 bp with a coding region containing 1272 bp, that translates into 424 amino acids. The total translation of rZP3 peptide has a molecular weight of 45,820, containing six potential N-glycosylation sites and 75 Ser/Thr residues, possible O-glycosylation sites. The amino acid sequence derived from the cDNA sequence shares high sequence homologies to mouse (90%), hamster (78%), and human (65%) ZP3 (ZPC) glycoproteins, indicating that the rat and mouse ZP3 have quite a conserved amino acid sequence, including the potential glycosylation sites. The total transcript of the rZP2 was 2154 nucleotides and the largest open reading frame was 695 amino acids. This would translate into a protein of 78.4 kDa. In the case of rZP1, the cDNA clone consisted of 1960 bp, and the coding region contained 1851 bp translating into 617 amino acids. Significant homologies were observed between rZP2 and ZPA family from various mammalian species. The rZP1 also showed a sequence homology to mouse ZP1, known as a mouse orthologue of ZPB family, suggesting that the rZP2 and rZP1 are members of ZPA and ZPB families, respectively. The message distributions for each zona components were limited within the ovary and the signal was detectable in the growing oocytes. The present results will further our understanding of the structure of rat zona components and lead to a better understanding of species-specificity observed during sperm-egg interaction.

Amino Acid Sequence↗

[Structure and assembly of human beta herpesviruses].

This review is concerned with the structure and assembly of HCMV, HHV6 and HHV7. A characteristic ultrastructural feature common to all these viruses is a distinct tegumentary coating of intracytoplasmic capsids. The tegument structure is also distinctly seen in the virions of HHV6 and HHV7. Morphologically, acquisition of the tegument was observed to have taken place in the cytoplasm. Immunoelectron microscopic studies of HCMV infected cells, however, have demonstrated the existence of a tegument protein, pp150, on the surface of intranuclear capsids as well as on capsids in the cytoplasm and in extracellular virions. In addition, another tegument protein, pp65 has been detected within the matrix of cytoplasmic and extracellular dense bodies but not in virions. The molecular mechanism of the assembly of beta herpesviruses was also discussed.

Capsid↗

Preventive effects of interleukin 1 beta for ACNU-induced myelosuppression in malignant brain tumors: the experimental and preliminary clinical studies.

The effect of recombinant human interleukin 1 beta (rHuIL-1 beta) on myelosuppression induced by 3-[(4-amino-2-methyl-5-pyrimidynyl)methyl]-1-(2-chloroethyl)-1-nit rosourea hydrochloride (ACNU) was studied. In in vivo study using BALB/c mice, pretreatment with 1 microgram/mouse of rHuIL-1 beta as a single intraperitoneal (i.p.) injection had a significant preventive effect on thrombocytopenia as well as granulocytopenia induced by ACNU at an intravenous dose of 60 mg/kg. Facilitated recovery by rHuIL-1 beta administered seven days after injection of high-dose ACNU was also observed. Experimental combination immunochemotherapy with high-dose ACNU and rHuIL-1 beta was performed in nude mice inoculated with human glioblastoma subcutaneously. The elongation of the survival time of the tumor bearing nude mice was also observed in combined use of high dose ACNU with rHuIL-1 beta. Seven patients with malignant brain tumors received intravenous 2.5-3 mg/kg ACNU. All patients were subcutaneously injected with 2 x 10(4)-U or more rHuIL-1 beta twice a week or daily. The mean nadir of leukocyte, granulocyte, and thrombocyte counts of the 7 patients received 2.5-3 mg/kg ACNU were significantly higher than in matched historical controls. In combination with rHuIL-1 beta, it may be possible to use chemotherapeutic agents at a relatively high dose.

Aged↗

Pharmacological studies of imidazoline derivatives. I. A comparison of the effect on pre- and postsynaptic alpha-adrenoceptors in the rat vas deferens.

The effects of 8 imidazoline derivatives on pre- and postsynaptic alpha-adrenoceptors and [3H]norepinephrine release were investigated in the rat vas deferens and were compared with those of reference drugs, yohimbine, phentolamine, tolazoline, and prazosin. K-6341 and K-6343 activated postsynaptic alpha 1-adrenoceptor and were antagonized by prazosin. The order of potency series as alpha 1-antagonist, prazosin greater than phentolamine greater than yohimbine greater than K-4011 greater than K-3827 greater than K-4300, tolazoline was found in antagonism against phenylephrine. Many derivatives exhibited an antagonistic action against clonidine, and the potency series as alpha 2-antagonist was revealed as follows: phentolamine greater than yohimbine greater than K-3827 greater than K-4011 greater than K-6341 greater than K-6343 greater than K-4300, tolazoline greater than prazosin greater than K-4299. The antagonistic effect was more selective on presynaptic (alpha 2) than postsynaptic (alpha 1) adrenoceptor and the rank order of selectivity (KB-post/KB-pre) was K-3827 greater than yohimbine greater than K-4011 greater than tolazoline, K-4300 greater than phentolamine greater than prazosin. Imidazoline derivative increased [3H]norepinephrine release, the actions of K-3827, K-6341 and K-4300 being particularly potent. From these results, the structure-activity relationship was summarized. First, when 2',3'-methylenedioxyphenyl group is connected with the imidazoline ring via an amino or methylene residue, these compounds become alpha 1-agonist. Secondly, when the methylenedioxyphenyl group and the imidazoline ring are connected via an amino residue, these compounds show a weak agonistic and potent antagonistic characteristics at the presynaptic alpha 2-adrenoceptor. Thirdly, an addition of a methylenedioxy radical to the phenyl ring increased the affinity of the compounds to presynaptic alpha 2-receptor.

Animals↗

Pharmacological studies of imidazoline derivatives. II. Agonistic and antagonistic actions on alpha-adrenoceptors in various smooth muscle preparations.

The effects of 8 imidazoline derivatives on alpha-adrenoceptor-mediated contraction or relaxation of various kinds of smooth muscle preparations were investigated. In rabbit aortic strips, K-6341, K-6343 and K-4011 produced alpha-agonistic action which was antagonized by prazosin. In the study of alpha-antagonistic action of imidazoline derivatives, i.e. antagonism against norepinephrine- or phenylephyrine-induced contraction of the rabbit aortic strip, the order of potency series, prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300 greater than tolazoline was found. Reserpine pretreatment did not affect the results. In the study of alpha-antagonistic effect on the relaxing response to norepinephrine of methacholine-contracted rat ileum, the potency series was revealed as follows: prazosin greater than phentolamine greater than yohimbine greater than K-4011, K-3827, K-4300, tolazoline. A similar experiment was performed on histamine-contracted guinea-pig taenia coli, and the results were nearly identical to the case of the rat ileum, except that K-6341 and K-6343 also exhibited alpha-antagonistic action which was not detected in the rat ileum. This suggests that alpha 2-receptor may exist in the postsynaptic alpha-adrenoceptor in the guinea-pig taenia coli. The results of the present study indicate that the potency of imidazoline derivatives to inhibit norepinephrine-induced contraction of some smooth muscle is almost identical to that which inhibited norepinephrine-induced relaxation of other smooth muscles. Furthermore, K-4300 was found to possess anti-acetylcholine and anti-histamine actions in the guinea-pig taenia coli and anti-serotonin action in the rat fundus strips.

Acetylcholine↗

Pharmacological studies of imidazoline derivatives. III. Actions on cardiovascular system and acute toxicity.

The effects of 8 imidazoline derivatives on the cardiovascular system and their acute toxicity were investigated. In anesthetized rats, K-6341 and K-6343 produced relatively long-lasting elevation of blood pressure. This hypertensive response was prevented by prazosin. In contrast, K-4011, K-3827 and K-4300 exerted long-lasting hypotensive actions. Norepinephrine-induced increase in blood pressure was competitively antagonized by these three derivatives. Therefore, the hypertensive and hypotensive actions of imidazoline derivatives are conceivably exerted by activating and blocking alpha 1-adrenoceptors. In the isolated guinea-pig atrial preparations, K-4011, K-3827, K-6341 and K-6343 produced positive inotropic responses which were independent of beta-adrenoceptor activation. The positive inotropic effect of K-6341, which was the most potent, was specifically attenuated or abolished by diltiazem, suggesting that a change in Ca2+ movement across the cell membrane is contributing to K-6341-induced increase in atrial contractions. The main symptoms of mice manifested when injected with imidazoline derivatives were a decrease in spontaneous movement, exophthalmos, an increase in palpebral opening, paralysis of four limbs and respiratory depression. Acute LD50 values of imidazoline derivatives in mice (i.v., i.p.) were between these of tolazoline and naphazoline.

Animals↗

Ultrastructures of leuco-adsorption on monolayers infected with influenza virus.

Leuco-adsorption occurring in influenza virus infected-cell cultures was studied morphologically to clarify the mechanisms of adsorption of leukocytes. Among the various types of chicken leukocytes studied, such as lymphocytes, monocytes, granulocytes, and thrombocytes, all were found to adhere to the virus-infected cells. The adsorption seems to occur through at least two processes, one is mediated by microvilli (microvillus-attachment), and the other is direct adherence of both cells (cell-to-cell-attachment). In the former, the leukocytes are bound to the microvilli protruding from the infected MDCK cells and in the latter both cell membranes attach directly. In the cell-to-cell-attachment, there was an electron-lucent gap of about 12 nm in width in the intermembranous space of the junctional regions. This region was similar morphologically to the gap junction. As a result of leucoadsorption no cytolytic effects occurred in the MDCK cells under the experimental conditions.

Adsorption↗

Electron microscopic study on vaccinia virus release.

FL cells infected with the IHD-W strain of vaccinia virus were studied by scanning and transmission electron microscopy. A large number of naked virus particles were found to accumulate beneath the host cell plasma membrane and to protrude from the cell surface. It was seen in some cases that naked viral particles were released by budding not only from the cell surface but also from the surface of cytoplasmic packets which were seen along the cell periphery.

Amnion↗

[Reproduction study of Guanabenz, a new antihypertensive agent (2) - teratological test in rats].

Guanabenz (WY-8678) was given to pregnant rats to examine its effects on dams, their fetuses, and offspring. The drug was administered orally to rats at 15, 5 and 1 mg/kg/day from the 7th days of gestation. The vehicle used was 5%-Arabic Gum at dose level of 5 ml/kg, and a control experiment where only the vehicle was administered was also conducted. The results obtained were as follows. 1. In the observation of the dams, the increase of body weight tended to be repressed in the 15 mg/kg group, and body weight decreased in the 30 mg/kg group. 2. The drug produced decreased spontaneous movement, sedation, and lacrimation of red exudate in dams. 3. Half of the 30 mg/kg group had a resorption, but there were no remarkable effects on length of gestation and nursing in the nursing group. 4. The weight of the thymus decreased dose-dependency. 5. No difference was observed in each group in the number of corpora lutea, the number of resorptions, the number of live fetuses, sex ratio, and mean placental weight of the fetuses. The mean body weight of the fetuses decreased in the 30 and among 15 mg/kg groups. 6. In observation of the fetuses, no difference was observed among groups regarding external and visceral malformations. In the skeletal observation, retardation of ossification of the forelimb and hind limb was observed in the 30 and 15 mg/kg groups, and retardation of ossification of the sternebra was observed in the 30 mg/kg group. 7. In observation of the offspring, the number of implantations, the number of live fetuses, delivery rate, and viability rate decrease in the 30 mg/kg group. No difference was observed among groups as to postnatal development symptoms, the faculties of sensation, and emotion. From these results, it is conducted that Guanabenz has no teratogenic potential in rats and the safe dosage levels seems to be below 5 mg/kg/day.

Abnormalities, Drug-Induced↗