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Biomedical subjects

M Takase

Publications and source records attributed to M Takase.

At least 109 records · Page 6Linked to original sources

[Transcranial magnetic stimulation of the facial nerve--identification of the actual excitation site in the cat].

The site where transcranial magnetic stimulation excites the facial nerve was studied in 6 cats. Transcranial magnetic stimulation of the facial nerve was recorded from the left mentalis muscle. A figure-of-eight shaped magnetic coil was used, and coil induction direction had more influence on the facial nerve evoked compound muscle action potentials (CMAPs) than the coil position. No change could be detected in the CMAPs before and after craniotomy, after cerebellar lobectomy and after exposure of the facial nerve in the facial canal. The facial nerve was stimulated electrically at the porus, meatal portion, geniculum and horizontal portion. The latencies of the CMAPs for each portion were measured and compared with the magnetic response, which was coincidental with that of the meatal portion. The facial nerve was then transected distally from the porus, and CMAPs following magnetic stimulation were recorded at each step. The CMAPs disappeared when the nerve was transected at the fundus. The results of both approaches in this study led to the conclusion that transcranial magnetic stimulation excites the facial nerve at the meatal portion.

Action Potentials↗

[Lactoferrin in cervical mucus of patients with chorioamnionitis].

The antimicrobial activity of cervical mucus is regarded as a local defense mechanism against ascending infections by the vaginal bacterial flora. In this study, the content of lactoferrin in cervical mucus of patients with chorioamnionitis (CAM) and its correlation with other indicators of infection were determined. The results obtained are summarized as follows: 1. The lactoferrin content in cervical mucous was higher in pregnant than in non-pregnant women. It was significantly lower in CAM(+) patients than in CAM(-) patients (P < 0.001) in preterm labor and was lower in preterm labor than in full-term control (P < 0.002). Elastase contents in cervical mucus of CAM(+) patients were significantly higher than full-term control levels (P < 0.001), and showed a negative correlation with lactoferrin contents. 2. With regard to other indicators of infection, CRP, ESR, and WBC were higher in CAM(+) patients and fibronectin was detected (> 50 ng/ml) in the cervical mucus of all CAM(+) patients.

Cervix Mucus↗

Cloning and sequencing of the cDNA encoding tyrosinase of the Japanese pond frog, Rana nigromaculata.

We cloned and sequenced the cDNA encoding tyrosinase (TYN) of the Japanese pond frog, Rana nigromaculata. The 3511-bp cDNA contained a 54-bp 5'-noncoding region, a 1596-bp open reading frame encoding TYN of 532 amino acids (aa), and a 1861-bp 3'-noncoding region. The aa sequence of frog TYN predicted from the cDNA sequence was homologous to that of mouse and human TYNs. The aa sequence including the copper-binding domain, which is likely the active center of TYN, was highly conserved among these three species and Neurospora crassa, Streptomyces antibioticus, and S. glaucescens. The frog TYN also contains possible glycosylation sites and conserved Cys at sites similar to those in the mouse and human TYNs. There are two hydrophobic regions at the N-terminus and near the C-terminus, which are likely the signal (leader) peptide and a transmembrane domain, respectively.

Amino Acid Sequence↗

Identification of the bactericidal domain of lactoferrin.

We report the existence of a previously unknown antimicrobial domain near the N-terminus of lactoferrin in a region distinct from its iron-binding sites. A single active peptide representing this domain was isolated following gastric pepsin cleavage of human lactoferrin, and bovine lactoferrin, and sequenced by automated Edman degradation. The antimicrobial sequence was found to consist mainly of a loop of 18 amino acid residues formed by a disulfide bond between cysteine residues 20 and 37 of human lactoferrin, or 19 and 36 of bovine lactoferrin. Synthetic analogs of this region similarly exhibited potent antibacterial properties. The active peptide of bovine lactoferrin was more potent than that of human lactoferrin having effectiveness against various Gram-negative and Gram-positive bacteria at concentrations between 0.3 microM and 3.0 microM, depending on the target strain. The effect of the isolated domain was lethal causing a rapid loss of colony-forming capability. Our studies suggest this domain is the structural region responsible for the bacterial properties of lactoferrin.

Amino Acid Sequence↗

In vivo anti-tumor activity of arginine deiminase purified from Mycoplasma arginini.

Arginine deiminase (EC 3.5.3.6) was purified to homogeneity from the cell extract of Mycoplasma arginini by molecular-sieve, anion-exchange and arginine-affinity chromatographies. The purified enzyme was composed of 2 identical sub-units with a molecular weight of 45.000 and had a pI of 4.7. Its Vmax value and Km value for L-arginine were estimated to be 50 units/mg protein and 0.2 mM, respectively. It exerted maximal enzyme activity at pH 6.0-7.5 and at 50 degrees C. The arginine deiminase was stable at neutral pH. When injected i.v. into mice, the half-life of the arginine deiminase in blood was about 4 hr. In culture, the enzyme strongly inhibited the growth of 6 kinds of mouse tumor cell lines by depleting L-arginine in the culture media. When the in vivo growth-inhibitory activity of arginine deiminase was tested for the 6 tumor cell lines, i.p. administration of the purified enzyme effectively prolonged the survival time of the mice injected with all kinds of the tumor cell lines. Especially, the in vivo growth of a hepatoma cell line, MH134, was completely prevented by the daily administration at a dose of 0.2 mg/mouse for 14 days. These results raise the possibility of the use of the arginine deiminase derived from Mycoplasma arginini as a new anti-tumor drug.

Animals↗

Antibacterial spectrum of lactoferricin B, a potent bactericidal peptide derived from the N-terminal region of bovine lactoferrin.

A physiologically diverse range of Gram-positive and Gram-negative bacteria was found to be susceptible to inhibition and inactivation by lactoferricin B, a peptide produced by gastric pepsin digestion of bovine lactoferrin. The list of susceptible organisms includes Escherichia coli, Salmonella enteritidis, Klebsiella pneumoniae, Proteus vulgaris, Yersinia enterocolitica, Pseudomonas aeruginosa, Campylobacter jejuni, Staphylococcus aureus, Streptococcus mutans, Corynebacterium diphtheriae, Listeria monocytogenes and Clostridium perfringens. Concentrations of lactoferricin B required to cause complete inhibition of growth varied within the range of 0.3 to 150 micrograms/ml, depending on the strain and the culture medium used. The peptide showed activity against E. coli O111 over the range of pH 5.5 to 7.5 and was most effective under slightly alkaline conditions. Its antibacterial effectiveness was reduced in the presence of Na+, K+, Mg2+ or Ca2+ ions, or in the presence of various buffer salts. Lactoferricin B was lethal, causing a rapid loss of colony-forming capability in most of the species tested. Pseudomonas fluorescens, Enterococcus faecalis and Bifidobacterium bifidum strains were highly resistant to this peptide.

Amino Acid Sequence↗

[Quantitative analyses of the normal throat flora of children with upper respiratory tract infections].

Relationship between the normal throat flora and pathogenic bacteria recovered from the throat in 139 children with upper respiratory tract infections in winter were studied using quantitative analyses. Pathogenic bacteria examined include S. pyogenes, H. influenzae, S. aureus, and S. pneumoniae, and the normal floras include alpha-streptococci, gamma-streptococci, Neisseria species, and Micrococci. Children with S. pyogenes in their throats (S. pyogenes group) were examined with anti-streptococcal antibodies such as anti-streptolysin O, anti-streptokinase, and anti-deoxyribonuclease B. Eighty seven pathogenic bacteria were recovered from 72 children (51.8%) out of 139. S. pyogenes and S. pneumoniae groups showed significantly lower alpha-streptococci and gamma-streptococci in incidence of appearance when compared with children with the no pathogenic bacteria in their throats (no bacteria group). H. influenzae group showed significantly lower gamma-streptococci and higher Neisseria sp. in incidence of appearance compared with the no bacteria group. Positive cases for anti-streptococcal antibodies showed a significantly lower alpha-streptococci in number compared with negative cases for antibodies and the no bacteria group, and a significantly lower gamma-streptococci in incidence of appearance compared with the no bacteria group. These data suggest that the normal throat flora may have a role in prevention of colonization by the pathogenic bacteria in vivo, as were shown in vitro by many authors, and that the quantitative analysis of the normal flora is useful because this methodology might reveal whether the bacteria recovered from the throat show the pathogenicity.

Adolescent↗

Absorption enhancement of polypeptide drugs by cyclodextrins. I. Enhanced rectal absorption of insulin from hollow-type suppositories containing insulin and cyclodextrins in rabbits.

The absorption of insulin (from porcine pancreas) from the rectum of rabbits after the administration of hollow-type suppositories containing insulin and five kinds of cyclodextrins (CyDs) was investigated. Three types of suppositories were employed: suppository I containing insulin (approximately 26 IU/mg) and various amounts of each CyD in citric buffer solution at pH 3.0 or powder in its cavity, suppository II containing CyD without insulin, and suppository III containing insulin without CyD. Without CyD, the insulin and glucose levels in plasma were unchanged, whereas a significant increase in the plasma insulin concentration and a marked decrease in the glucose levels were found following simultaneous administration of insulin and CyDs by suppository I. The enhancing effect of CyD on rectal insulin absorption (absorption-enhancing effect) by chemically modified CyDs (heptakis(2,6-di-O-methyl)-beta-CyD (DM-beta-CyD) and 2-hydroxypropyl-beta-CyD (HP-beta-CyD)) was higher than those by natural CyDs (alpha-, beta-, and gamma-CyD). The area under the plasma concentration-time curve (AUC) and Cmax of insulin significantly decreased with the preadministration (administration of CyD 6, 24 and 48 h before rectal insulin administration) of DM-beta-CyD. The absorption-enhancing effect disappeared 24 h after preadministration. These results suggest that CyDs enhance insulin absorption from the rectum, and that attenuation of the membrane transport barrier function in the rectum recovers at a maximum of 24 h after administration of CyDs.

Absorption↗

Spontaneous disappearance of arteriovenous fistula between the vertebral artery and deep cervical vein--case report.

A 58-year-old female was readmitted with pulsatile tinnitus in the right ear 8 months after subtemporo-occipital transtentorial clipping of a peripheral superior cerebellar artery aneurysm. On examination, she was normal except for pulsatile bruit over the right mastoid region. Angiography showed a fistulous communication between the muscular branches of the right vertebral artery and the deep cervical vein. The incision of the aneurysm surgery was supratentorial, so the only possible cause of the upper cervical arteriovenous (AV) fistula was fine gold acupuncture needles implanted for bronchial asthma 18 years before. The AV fistula disappeared spontaneously after 1 month, possibly because of thrombosis of the affected veins.

Arteriovenous Fistula↗

[Ocular effects of topical instillation of UF-021 ophthalmic solution in healthy volunteers].

Phase I studies, as divided into two stages, were conducted in healthy volunteers with the ophthalmic solution of UF-021, a novel prostaglandin metabolite-related compound, that was reported to exhibit potent intraocular pressure (IOP)-reducing activity in various species of animals. In the first stage, the vehicle as well as UF-021 ophthalmic solutions at concentration of 0.03%, 0.06% and 0.09% were applied topically to the eyes of 8 healthy volunteers to determine their respective effects through observations on the IOP, and local ocular and systemic side effects. In the second stage, 2 dosages of UF-021 ophthalmic solution, 0.06% and 0.12%, were applied topically to 11 healthy volunteers to investigate the IOP-reducing activities and local ocular side effects. The results revealed that ophthalmic solutions of UF-021 at concentrations ranging from 0.03% to 0.12% reduced IOP in a dose-dependent manner with neither systemic nor local ocular controversial side effects at those dosage levels. In summary, UF-021 ophthalmic solutions, when administered to healthy volunteers through single instillation, reduced IOP significantly without causing any side effects.

Administration, Topical↗

[A mechanism for reducing intraocular pressure in normal volunteers using UF-021, a prostaglandin-related compound].

The mechanism of reduction of intraocular pressure (IOP) and other ocular effects were studies after topical application of prostaglandin (PG) F2 alpha and UF-021, a new PG related compound, in eight normal volunteers. IOP, aqueous humor flow rate and outflow rate were evaluated during a period of four hours after the application. Both PGF2 alpha and UF-021 caused significant and similar IOP reduction for four hours. Neither compound produced any significant change in the aqueous humor flow rate or outflow rate, suggesting the increase of unconventional outflow rate as being the possible mechanism of IOP reduction in normal human eyes.

Adult↗

Antitumor activities and schedule dependence of orally administered MST-16, a novel derivative of bis(2,6-dioxopiperazine).

We studied bioavailability, treatment schedule dependence, and therapeutic efficacy of orally administered MST-16, a novel derivative of bis(2,6-dioxopiperazine), against murine tumors and human tumor xenografts. The rate of its intestinal absorption was about 50%, and it was immediately metabolized to its parent compound, ICRF-154. Therapeutic efficacy of MST-16 was heavily dependent on the treatment schedule: 9 daily oral administrations and treatment every 4 h on day 1 only were much more effective against s.c.-implanted L1210 leukemia than a single dose or five daily administrations giving the same total dose. Orally administered MST-16 showed potent life-prolonging effects (196%, 219% and 148%) in mice inoculated i.p. with P388, L1210 leukemia, and C-26 colon adenocarcinoma, respectively, but had no effect on B16 melanoma inoculated in the same way. MST-16 inhibited more than 80% growth of Lewis lung carcinoma, B16 melanoma, and C-38 colon adenocarcinoma implanted s.c., but had only a minor effect on M5076 fibrosarcoma. Lung metastasis of Lewis lung carcinoma was also effectively suppressed. Furthermore, MST-16 significantly inhibited growth of human colon, lung and breast cancers implanted s.c. in nude mice. We also made a kinetic analysis of the in vitro cell-killing effect by ICRF-154, the active form of MST-16 in vivo. It demonstrated a cell cycle phase-specific and time-dependent action, providing a reasonable explanation for the schedule-dependent therapeutic effect of MST-16.

Administration, Oral↗

[Synthesis and antifungal activity of butenafine hydrochloride (KP-363), a new benzylamine antifungal agent].

In screening of new antifungal agents, bis(naphthalenemethyl)amines were found to have more potent antifungal activity than clotrimazole. Studies on their structure-activity relationships indicated that benzylamines had potent antifungal activity. Among them, butenafine hydrochloride (N-p-tert-butylbenzyl-N-methyl-1-naphthalenemethylamine hydrochloride, KP-363) has proved to show the strongest activity. It exhibits a wide spectrum activity in vitro against particularly dermatophytes (87 strains; minimal inhibitory concentration (MIC) range, 0.0015 to 0.05 microgram/ml), and also against Aspergillus (15 strains; MIC range, 0.025 to 0.78 microgram/ml), Cryptococcus neoformans (4 strains; MICs 0.78 and 1.56 micrograms/ml) and yeasts of genus Candida (67 strains; MIC range, 3.13 to greater than 100 micrograms/ml).

Animals↗

Potent antibacterial peptides generated by pepsin digestion of bovine lactoferrin.

The antibacterial properties of enzymatic hydrolysates of bovine lactoferrin were examined to determine whether active peptides are produced from this protein. Hydrolysates prepared by cleavage of lactoferrin with porcine pepsin, cod pepsin, or acid protease from Penicillium duponti showed strong activity against Escherichia coli O111, whereas hydrolysates produced by trypsin, papain, or other neutral proteases were much less active. Low molecular weight peptides generated by porcine pepsin cleavage of lactoferrin showed broad-spectrum antibacterial activity, inhibiting the growth of a number of Gram-negative and Gram-positive species, including strains that were resistant to native lactoferrin. The antibacterial potency of the hydrolysate was at least eightfold greater than that of undigested lactoferrin with all strains tested. The active peptides retained their activity in the presence of added iron, unlike native lactoferrin. The effect of the hydrolysate was bactericidal as indicated by a rapid loss of viability of E. coli O111. The lactoferrin hydrolysate described in the present study has commercial value as a natural preservative agent for use in foods and cosmetics, and as a functional component of new clinical foods for prevention or treatment of gastrointestinal disease.

Animals↗

[[Population, birth, and death in Japan for the period 1890-1920]].

"Japanese mortality statistics since 1872 show upward [trends] in overall mortality until 1920, and thereafter mortality goes down. Whether this was true or just...caused by improvement in [the] death registration rate has been a matter of debate. The author tried to examine the accuracy and completeness of death registration data for the period 1890-1920....[It is found that] registered mortality data for the period 1890-1920 are believed to be highly reliable and would be a valuable source of data for the study of the early stage of mortality transition." (SUMMARY IN ENG)

Asia↗

Effects of topical application of UF-021, a novel prostaglandin derivative, on aqueous humor dynamics in normal human eyes.

The mechanism underlying the intraocular pressure (IOP) lowering effect of a prostaglandin-related compound, isopropyl 20-ethyl-9 alpha,11 alpha-dihydroxy-15-keto-cis-delta 5-prostanoate (UF-021), and its possible adverse effects in long-term use were studied in normal human eyes. A single instillation of 0.12% UF-021 significantly lowered IOP without affecting aqueous flow rate, tonographic C value or episcleral venous pressure. Protein concentration in the anterior chamber and corneal endothelial permeability to fluorescein remained unaffected. It was suggested that UF-021 lowers IOP mainly by increasing uveoscleral outflow. Twice daily application of 0.12% UF-021 for 4 weeks caused no significant changes in aqueous protein concentration, aqueous flow rate or corneal endothelial permeability. Neither single nor long-term use of topical UF-021 induced irritative responses in the outer segment of the eye. The present study suggests that UF-021 has potential as a safe and effective ocular hypotensive drug with a mechanism of action different from other drugs currently available for the treatment of glaucoma.

Administration, Topical↗

Effects of prolactin and bromocryptine on the regulation of testicular luteinizing hormone receptors in mice.

The binding of luteinizing hormone (LH) to testicular homogenates increased gradually in mice from 15 to 60 days of age, while the level at 90 days was almost the same as that at 60 days. The plasma concentration of prolactin (PRL) increased significantly from 15 to 40 days and thereafter remained constant. In order to ascertain the influence of PRL on testicular receptors for LH, bromocryptine was injected subcutaneously for 10 days into immature (20-day-old) and adult (90-day-old) mice. In 20-day-old mice, treatment with bromocryptine significantly reduced the plasma levels of PRL but had no significant effects on the binding of LH to receptors in 30-day-old mice. However, in 90-day-old mice, treatment with bromocryptine led to a significant reduction in numbers of receptors for LH 10 days later. There was no difference in dissociation constants (Kd) between groups of oil-injected (Kd = 6.5 x 10(-10) M) and bromocryptine-injected (Kd = 4.6 x 10(-10) M) mice. The reduction in binding of LH per testis of 100-day-old mice after treatment with bromocryptine was eliminated by the simultaneous administration of ovine (o) PRL. The plasma level of follicle-stimulating hormone (FSH) in 100-day-old mice, which tended to be decreased as a result of treatment with bromocryptine, was markedly increased by treatment with oPRL. There were no distinct changes in binding of FSH in any of the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Antitumor activity of MST-16, a novel derivative of bis(2,6-dioxopiperazine), in murine tumor models.

We studied the antitumor activity of newly synthesized bis(1-acyloxymethyl) derivatives of 4,4'-(1,2-ethanediyl)bis(2,6-piperazinedione) using i.p.-i.p. models of P388 leukemia and B16 myeloma. As a result, we found 4,4'-(1,2-ethanediyl)bis(1-isobutoxycarbonyloxymethyl-2,6-piperazi nedione) (MST-16) to possess considerable therapeutic activity. MST-16 showed not only marked life-prolonging effects in both P388 leukemia- and B16 melanoma-bearing mice but also a greater therapeutic ratio than did its parent compounds, ICRF-154 and ICRF-159. Further studies revealed that MST-16 has considerable therapeutic activity against a number of other tumors such as ascitic forms of L1210 leukemia, colon 26 adenocarcinoma, and MH-134 hepatoma and solid forms of B16 melanoma, Lewis lung carcinoma, colon 38 adenocarcinoma, and M5076 fibrosarcoma. These results suggest that MST-16 is very promising as an antitumor agent.

Animals↗