Biomedical subjects

K Nakata

Publications and source records attributed to K Nakata.

At least 199 records · Page 11Linked to original sources

PubMed1998

Involvement of macrophage scavenger receptors in protection against murine malaria.

Macrophage scavenger receptor A (MSR-A) deficient mice MSR-A(-/-) were infected by the intraperitoneal injection of the Plasmodium berghei NK65 strain in the erythrocytic stage. The MSR-A(-/-) mice died significantly earlier than the control mice (P=0.060). In the surviving mice, two peaks of parasitemia were observed: the first 5-7 days and the second at 2-3 weeks after infection. Death of all MSR-A(-/-) mice occurred at either peak of parasitemia, suggesting that MSR-A protects mice from severe infection. This model may be useful for the study of molecular mechanisms of macrophage functions in malaria infection.

Animals↗

PubMed1998

[Development of NIHS Information and Computing Infrastructure (NICI)].

We describe the development of NICI, which we extended during June 1996 to May 1998. The direct lines between our Experimental Stations for Medicinal Plants at Tsukuba and Tsukuba Node for Inter Ministry Network, and newly opened Pharmaceuticals and Medical Devices Evaluation Center at Minato-ku and NIHS at Setagaya-ku in Tokyo, were constructed. Although the main frame in NIHS at Setagaya is not different since May 1996, we provided many databases and useful information on Drugs, Foods and Chemicals, constructing the interface between World Wide Web and databases. Our Home Page was timely updated.

Databases, Factual↗

PubMed1998

[Dissemination of drug information by the Internet].

We reported a system for dissemination of the drug information and its related subjects through the Internet (Drug Info Guide) in Bull. Natl. Inst. Health Sci. 1996. Since then, further information were added in the system. These include the web site for ICH Guideline in Japanese and English, and Australasian Cochrane Centre mirror site. Furthermore, the titles and their abstracts which were reviewed by Cochrane groups in Cochrane Library were translated in Japanese, and these information together with the search guide for useful resource regarding the drug information were also presented on WWW.

Databases, Factual↗

PubMed1998

Different alleles cause an imbalance in A2 and A2B phenotypes of the ABO blood group.

BACKGROUND AND OBJECTIVES: In several populations, including the Japanese, the frequency of the A2B phenotype is significantly higher than expected based on the A2 phenotype frequency. To understand the genetic basis of this 'excess' of A2B, we examined ABO alleles in individuals with A2-related phenotypes. MATERIALS AND METHODS: ABO alleles were identified by means of polymerase chain reaction single-strand conformation polymorphism (SSCP) and nucleotide sequence analyses. RESULTS: The frequencies of A2-related alleles (*A105, *A106, *A107, *A111 and *R101) were clearly different between the A2 and A2B phenotypes. In particular, a putative recombinant allele, *R101, was uncommon in the A2 but common in the A2B phenotype individuals. This allele was also detected in 4 of 401 (1%) unrelated A1 phenotype (AO genotype) individuals. CONCLUSION: *R101 is presumably expressed as phenotype A1 in *R101/*O heterozygous individuals, but as phenotype A2 in *R101/*B heterozygotes, thus giving rise to a high A2B phenotype frequency.

ABO Blood-Group System↗

PubMed1998

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (1996)].

The bacteria isolated from the patients with lower respiratory tract infections were collected by institutions located throughout Japan, since 1981. Ikemoto et al. have been investigating susceptibilities of these isolates to various antibacterial agents and antibiotics, and characteristics of the patients and isolates from them each year. Results obtained from these investigations are discussed. In 16 institutions around the entire Japan, 557 strains of presumably etiological bacteria were isolated mainly from the sputa of 449 patients with lower respiratory tract infections during the period from October 1996 to September 1997. MICs of various antibacterial agents and antibiotics were determined against 98 strains of Staphylococcus aureus, 93 strains of Streptococcus pneumoniae, 84 strains of Haemophilus influenzae, 84 strains of Pseudomonas aeruginosa (non-mucoid strains), 17 strains of Pseudomonas aeruginosa (mucoid strains), 31 strains of Moraxella subgenus Branhamella catarrhalis, 21 strains of Klebsiella pneumoniae etc., and the drug susceptibilities of these strains were assessed except for those strains that died during transportation. 1) S. aureus S. aureus strains for which MICs of oxacillin (MPIPC) were higher than 4 micrograms/ml (methicillin-resistant S. aureus) accounted for 67.3%. The frequency of the drug resistant bacteria increased comparing to the previous year's 52.7%. Arbekacin (ABK) and vancomycin (VCM) showed the highest activities against both S. aureus and MRSA with MIC80s of 1 microgram/ml. 2) S. pneumoniae Imipenem (IPM) and panipenem (PAPM) of carbapenems showed the most potent activities with MIC80s of 0.063 microgram/ml. Faropenem (FRPM) showed the next potent activity with MIC80 of 0.125 microgram/ml. The other drugs except erythromycin (EM), clindamycin (CLDM) and tetracycline (TC) were active against S. pneumoniae tested with MIC80s of 8 micrograms/ml or below. 3) H. influenzae The activities of all drugs were potent against H. influenzae tested with MIC80s of 4 micrograms/ml or below. Cefotiam (CTM), cefmenoxime (CMX), cefditoren (CDTR) and ofloxacin (OFLX) showed the most potent activities with MIC80s of 0.063 microgram/ml. 4) P. aeruginosa (mucoid strains) Tobramycin (TOB) showed the most potent activity against P. aeruginosa (mucoid strains) with MIC80 of 1 microgram/ml. Ceftazidime (CAZ), cefsulodin (CFS), IPM, gentamicin (GM), ABK and ciprofloxacin (CPFX) showed the next potent activities, with MIC80s of 2 micrograms/ml. The MIC80s of the other drugs ranged from 4 micrograms/ml to 16 micrograms/ml. 5) P. aeruginosa (non-mucoid strains) TOB and CPFX showed the most potent activities against P. aeruginosa (non-mucoid strains) with MIC80s of 1 microgram/ml. The MIC80s of piperacillin (PIPC) and cefoperazone (CPZ) were 16 micrograms/ml in 1995, and they were 64 micrograms/ml in 1996. 6) K. pneumoniae All drugs except ampicillin (ABPC) were active against K. pneumoniae. CMX, cefpirome (CPR), cefozopran (CZOP) and carumonam (CRMN) showed the most potent activities against K. pneumoniae with MIC80s of 0.125 microgram/ml. The MIC80s of the other drugs ranged from 0.25 microgram/ml to 2 micrograms/ml. 7) M.(B) catarrhalis Against M.(B.) catarrhalis, all drugs showed good activities with MICs of 4 micrograms/ml or below. IPM and minocycline (MINO) showed the most potent activities with MICs of 0.063 microgram/ml. Also, we investigated year to year changes in the characteristics of patients, their respiratory infectious diseases, and the etiology. Patients' backgrounds were examined for 557 isolates from 449 cases. The examination of age distribution indicated that the proportion of patients with ages over 60 years was 71.0% of all the patients showing a slight increase over that in 1994. Proportions of diagnosed diseases were as follows: Bacterial pneumonia and chronic bronchitis were the most frequent with 35.9% and 30.3% respectively. They were followed by bronchiectasis with a proportion of 10.

Adult↗

PubMed1997

The HMC-1 human mast cell line expresses the hepatocyte growth factor receptor c-met.

Hepatocyte growth factor (HGF) was originally characterized as a strong inducer of liver regeneration. However, it is now clear that HGF and its receptor, the proto-oncogene c-met, can be expressed in many other tissues, and that HGF can mediate diverse biological activities. We investigated the expression and function of c-met in a human mast cell line (HMC-1). We found that HMC-1 cells express c-met and that c-met expression can be upregulated by treatment of the cells with phorbol 12-myristate 13-acetate (PMA). Although HGF did not detectably influence the proliferation or morphology of HMC-1 cells, HGF inhibited the cells' ability to release tumor necrosis factor-alpha (TNF-alpha) in response to stimulation with PMA and the calcium ionophore, A23187. These results add the inhibition of TNF-alpha production to the other recognized effects of HGF/c-met on cellular function.

Calcimycin↗

PubMed1997

Xenopus Zic3, a primary regulator both in neural and neural crest development.

Xenopus Zic3 is a Xenopus homologue of mouse Zic and Drosophila pair-rule gene, odd-paired. We show here that Zic3 has significant roles both in neural and neural crest development in Xenopus embryo. Expression of Zic3 is first detected in prospective neural plate region at gastrulation. Onset of the expression was earlier than most proneural genes and followed chordin expression. The expression was induced by blockade of BMP4 signal. Overexpression of Zic3 resulted in hyperplastic neural and neural crest derived tissue. In animal cap explant, the overexpression of Zic3 induced expression of all the proneural genes and neural crest marker genes. These findings suggest that Zic3 can determine the ectodermal cell fate and promote the earliest step of neural and neural crest development.

Animals↗

PubMed1997

Chemical kindling induced by pentylenetetrazol changes cholecystokinin mRNA and peptide levels in rat frontal cortex.

Kindling model is useful to study the mechanism of learning and memory. Cholecystokinin (CCK) mRNA and CCK-like immunoreactivity (CCK-LI) levels in the hippocampus and frontal cortex of chemically kindled rats were determined at different time points. In the frontal cortex, chronic treatment with pentylenetetrazol (PTZ) (40 mg/kg per day for 8 days) increased CCK mRNA level at 7 days, and decreased CCK-LI level at 2 and 7 days after the last injection. However, neither CCK mRNA nor CCK-LI levels in the hippocampus changed. These results suggest that PTZ-induced kindling increases CCK mRNA expression and CCK-LI release in the frontal cortex.

Animals↗

PubMed1997

FK506-binding proteins regulate smooth muscle contractility by altering neurotransmitter release.

To determine the roles of FK506-binding proteins, receptors for the immunosuppressant FK506, in tachykinin release, we examined the effects of the FK506 derivative ascomycin, [3S-[3R[E(1S,3S,4S)],4S,5R,8S,9E,12R,14R,15S,16R,18S,1 9S,26aR]]-8-ethyl- 5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro- 5,19-dihydroxy- 3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16- dimethoxy- 4,10,12,18-tetramethyl-15,19-epoxy-3H-pyrido[2,1-c][1,4]oxaazacyclotr icosine -1,7,20,21(4H,23H)-tetrone, on the contractility of the rabbit iris sphincter muscle. Ascomycin (10(-7) to 10(-5) M) caused concentration-dependent contractions, which were greatly attenuated by preexposure to rapamycin (10(-5) M), a FK506 receptor antagonist. Similarly, this contractile effect was abolished by preexposure to FK888 (10(-6) M), a tachykinin receptor antagonist, and to capsaicin (10(-5) M), a tachykinin-depleting agent. L-type voltage-dependent Ca2+ channel blockers, nicardipine (10(-5) M) and verapamil (5 x 10(-5) M), inhibited the ascomycin-induced contraction, but the N-type channel blocker omega-conotoxin (10(-6) M) did not. These results suggest that ascomycin stimulates tachykinin release by its binding to FK506-binding proteins and the subsequent activation of L-type Ca2+ channels. Thus, FK506-binding proteins may regulate muscle contractility by altering transmitter release from peripheral tachykininergic nerves.

Animals↗

PubMed1997

Dwarfism and age-associated spinal degeneration of heterozygote cmd mice defective in aggrecan.

Mouse cartilage matrix deficiency (cmd) is an autosomal recessive disorder caused by a genetic defect of aggrecan, a large chondroitin sulfate proteoglycan in cartilage. The homozygotes (-/-) are characterized by cleft palate and short limbs, tail, and snout. They die just after birth because of respiratory failure, and the heterozygotes (+/-) appear normal at birth. Here we report that the heterozygotes show dwarfism and develop spinal misalignment with age. Within 19 months of age, they exhibit spastic gait caused by misalignment of the cervical spine and die because of starvation. Histological examination revealed a high incidence of herniation and degeneration of vertebral discs. Electron microscopy showed a degeneration of disc chondrocytes in the heterozygotes. These findings may facilitate the identification of mutations in humans predisposed to spinal degeneration.

Aggrecans↗

PubMed1997

X-ray study of beijeran sodium salts, a new galacturonic acid-containing exo-polysaccharide.

X-Ray fiber diffraction patterns were obtained from oriented films of sodium salts of a new uronic acid-containing polysaccharide (beijeran) both in its native, poly [-->3)-alpha-D-GalA-(1-->3)-beta-L-Rha-(1-->3)-alpha-D-Glc-O6Ac-(1 -->], and deacetylated forms. Initially the stretched films of both polysaccharides were amorphous, but the crystallinity was much improved by annealing at high temperature. The deacetylated specimen had higher crystallinity than the native. Both films showed similar X-ray fiber patterns indicating that these polysaccharides had similar unit cell dimensions and that the O-acetyl groups in the native beijeran chain did not disturb the regular array in the crystal having space group P21. All the visible reflections could be indexed in terms of a monoclinic unit cell with dimensions a = 1.277, b = 1.611, c (fiber axis) = 2.437 nm, and gamma = 96.79 degrees. The fiber axis length and the presence of (002) and (006) reflections indicated that the conformation was made up of two trisaccharide residues, in an extended two-fold helix.

Carbohydrate Conformation↗

PubMed1997

Efficacy of immunization of high-risk infants against hepatitis B virus evaluated by polymerase chain reaction.

The polymerase chain reaction (PCR) is a rapid and very sensitive method to detect viral genomes. In the present study, the efficacy of immunization against hepatitis B virus (HBV) of high-risk infants was evaluated by PCR. Twenty-nine infants born to 24 HBeAg-positive carrier mothers were given hepatitis B immune globulin (HBIG) at birth and thereafter received repeated inoculations of plasma-derived vaccine or HBIG, or both, within 1 year. Serum samples at 1 year following immunization were stored at -40 degrees C for later analysis using PCR to detect HBV-DNA. When HBV genomes were detected in infants, the DNA sequences in the S gene of HBV were determined. Of 29 infants, 2 were positive for HBV-DNA at the 1 year following immunization; one had the HBV containing only the wild-type sequence in the S gene and became negative for HBV-DNA during the follow-up period. In contrast, another had the HBV, which contained nucleotide substitutions that altered the expression of the common group-specific determinant "a" of the S gene and resulted in clinical hepatitis with viral persistence. PCR analysis suggests that immunization against HBV prevents effectively high-risk infants from mother-to-child transmission. Even then, however, it is possible that amino acid substitutions in the "a" determinant of the S gene are associated with failure of conventional immunization against HBV.

Amino Acid Sequence↗

PubMed1997

Gefarnate stimulates secretion of mucin-like glycoproteins by corneal epithelium in vitro and protects corneal epithelium from desiccation in vivo.

The effect of drugs for gastritis and gastric ulcer (ecabet sodium, gefarnate, teprenone, and troxipide) on the secretion of mucin-like glycoproteins from rat cornea were investigated in vitro and on a short-term, rabbit dry eye model in vivo. For the studies in vitro, cultured rat cornea sections (3 mm diameter) were incubated with radiolabeled sodium sulfate, rinsed, and then incubated for 30 min in the presence of one of the drugs. The culture media were reacted with Dolichos biflorus agglutinate (DBA)-lectin, and the radioactivity of DBA-bound mucin-like glycoproteins was measured. A cytotoxicity assay confirmed that mucin-like glycoproteins had not leaked from damaged cells. For studies in vivo, eye drop vehicle or drops containing gefarnate were instilled in the eyes of nine anesthetized rabbits, and then the eyes were kept open with specula for two hours. These rabbits and two control rabbits not subjected to ocular drying were killed, and their eyes were enucleated and stained with methylene blue. Corneal epithelial damage from desiccation was evaluated based on the extent of methylene blue staining. Among the four kinds of drugs for gastritis and gastric ulcers, only gefarnate significantly increased the mucin-like glycoprotein secretion from cultured rat corneas in vitro; this stimulatory effect of gefarnate was dose-dependent. In vivo, the instillation of gefarnate reduced corneal epithelial damage from desiccation in a dose-dependent fashion. These results suggest that gefarnate reduces desiccation of corneal epithelium, perhaps by stimulating secretion of mucin-like glycoproteins from corneal epithelium.

Animals↗

PubMed1997

Involvement of both L- and N-type voltage-dependent Ca2+ channels in KCl- and veratridine-evoked transmitter release from non-adrenergic, non-cholinergic nerves in the rabbit iris sphincter muscle.

To determine which types of voltage-dependent Ca2+ channels mediate tachykinin release in the isolated rabbit iris sphincter muscle, we examined the effects of several Ca2+ channel modulators on contractions induced by either an elevation of the extracellular KCl concentration or application of the Na+ channel activator veratridine. Contractions caused by either 45.9 mM KCl or veratridine (10 microM) were inhibited by spantide (10 microM), a tachykinin receptor antagonist, and capsaicin (10 microM), a tachykinin-depleting agent, but were not changed by atropine. Nicardipine, an L-type Ca2+ channel blocker, inhibited contractions induced by KCl and veratridine in a concentration-dependent manner. omega-Conotoxin GVIA (1 microM), an N-type Ca2+ channel blocker, inhibited only contractions induced by lower concentrations of KCl, both when applied alone and when combined with nicardipine. Bay K 8644, an L-type Ca2+ channel activator, caused a spantide- and nicardipine-sensitive contraction in muscles partially depolarized with 15.9 mM KCl, and enhanced contractions induced by 15.9 mM KCl and veratridine (2 microM). omega-Agatoxin IVA (0.3 microM), a P-type voltage-dependent Ca2+ channel blocker, did not affect contractions induced by either KCl or veratridine. Contractions induced by exogenous substance P were not modified by any of the Ca2+ channel blockers or by Bay K 8644. These results suggest that, in the rabbit iris sphincter muscle. L- and N-type voltage-dependent Ca2+ channels are involved in neurotransmitter release from tachykininergic nerves elicited by high KCl and by veratridine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1997

Effects of the immunosuppressant cyclosporin A on neurotransmitter release from peripheral non-adrenergic, non-cholinergic nerves.

This study was undertaken to determine the effect of the immunosuppressant cyclosporin A on neurotransmitter release from non-adrenergic, non-cholinergic nerves (tachykininergic nerves) in the rabbit iris sphincter muscle. Cumulative application of cyclosporin A (0.1 to 10 microM) caused a slow onset of contraction in a concentration-dependent manner. Both FK888 (1 microM) and capsaicin (10 microM), a substance P receptor antagonist and a substance P-depleting agent, respectively, inhibited the contractile effect of cyclosporin A, whereas atropine (1 microM) had no effect. Both cyclosporin A and capsaicin (10 microM) stimulated the release of substance P-like immunoreactivity in the iris. Neither the sodium channel blocker tetrodotoxin (1 microM), the N-type voltage-dependent Ca2+ channel blocker omega-conotoxin GVIA (1 microM) nor the P-type channel blocker omega-agatoxin IVA (0.2 microM) affected cyclosporin A (1 microM)-induced contraction. In contrast, the L-type Ca2+ channel blocker nicardipine (10 microM) inhibited this contractile effect. These results suggest that cyclosporin A stimulates substance P-like tachykinin release by activating L-type voltage-dependent Ca2+ channels, resulting in contraction of the rabbit iris sphincter muscle.

Animals↗

PubMed1997

SA4503, a novel cognitive enhancer, with sigma 1 receptor agonistic properties.

We found a potent and selective sigma 1 (sigma 1) receptor ligand, SA4503 (1-(3,4-dimethoxyphenethyl)-4-(3-phenylpropyl)piperazine dihydrochloride). This compound had a high affinity for sigma 1 receptor subtype (IC50 = 17 +/- 1.9 nM), but a low affinity for sigma 2 receptor subtype (IC50 = 1800 +/- 310 nM). The present study examines the effect of this compound on the central cholinergic functions, since sigma receptor has been reported to interact with the central cholinergic neurons. SA4503 elicited the increase in extracellular acetylcholine level in rat frontal cortex, while it did not affect the striatal acetylcholine level. On the other hand, tetrahydroaminoacridine (THA), an acetylcholinesterase (AChE) inhibitor, increased the extracellular acetylcholine level in both regions. Although both compounds had anti-amnesic effect against scopolamine-induced memory impairment, THA also induced catalepsy in rats. These results suggest that SA4503 may be a novel cognitive enhancer, with sigma 1 receptor agonistic properties. In addition, SA4503 does not cause striatal cholinomimetic side-effects, which is different from THA.

Acetylcholine↗

PubMed1997

Avulsion fracture of the anteromedial bundle of the anterior cruciate ligament.

The avulsion fracture of the tibial attachment site of the anterior cruciate ligament is relatively rare among adults. Although partial avulsion fracture of this site is very rare, complex forces exerted on the knee joint could produce this type of fracture. We report on an adult patient with an avulsion fracture of the attachment site of anteromedial bundle of the anterior cruciate ligament associated with injuries of lateral and medial collateral ligament and fibular fracture. We speculate varus stress in a flexed knee coupled with rotation between the femur and tibia caused this type of injury.

Adult↗

PubMed1997

M3 muscarinic receptor mediates regulation of protein secretion in rabbit lacrimal gland.

PURPOSE: To identify which muscarinic receptor subtypes mediate protein secretion in isolated rabbit lacrimal glands. To compare protein secretory profiles in vitro with those in rabbit tears. METHODS: Rabbit lacrimal gland slices were incubated with carbachol in the presence and absence of different muscarinic antagonists. Protein secretion into the incubation medium was characterized with a Bio-Rad protein assay dye reagent in conjunction with Laemmli's method of SDS-PAGE. The medium protein profile was compared to that in tear samples. RESULTS: Dose dependent increases in protein secretion were elicited by carbachol between 10(-7) and 10(-4) M. During the first 20 min period, a maximal increase of 64% above the basal level was seen at the highest concentration. With 10(-4) M carbachol, the response was transient because after 100 min it decreased to its basal level. The increases in protein secretion caused by 10(-4) M carbachol were completely suppressed in the presence of 10(-5) M atropine. On the other hand, the relatively selective M1 antagonist, pirenzepine, at concentrations from 10(-6) M to 10(-4) M, had no effect on either the basal levels or the stimulatory effects of carbachol. Similarly, the relatively selective M2 antagonist, gallamine, at concentrations from 10(-6) M to 10(-4) M, had no effect on either of these levels. In contrast, the relatively selective M3 antagonist, 4-DAMP, at concentrations from 10(-6) M to 10(-4) M, progressively suppressed the stimulated level of protein secretion elicited by 10(-4) M carbachol without affecting the basal level. The protein profiles found in the tears and in the incubation medium were similar to one another. CONCLUSION: In vitro rabbit lacrimal gland protein secretion is comparable to that in vivo. Cholinergic-mediated control of rabbit lacrimal gland protein secretion occurs through stimulation of the M3 muscarinic receptor subtype.

Animals↗