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Biomedical subjects

K Takayama

Publications and source records attributed to K Takayama.

At least 19 recordsLinked to original sources
PubMed1992

Difference in distribution of glutamate-immunoreactive neurons projecting into the subretrofacial nucleus in the rostral ventrolateral medulla of SHR and WKY: a double-labeling study.

Glutamate immunoreactivity was found in 19% and 21% of the neurons of the central autonomic nuclei projecting into the subretrofacial nucleus (SRF) in the rostral ventrolateral medulla of Wistar-Kyoto rat (WKY) and spontaneously hypertensive rat (SHR), respectively, using a double-labeling technique in combination with glutamate immunocytochemistry. Double-labeled neurons were distributed in 22 nuclei or subnuclei in the limbic system, hypothalamus, midbrain, pons and medulla. The average number of glutamate-immunoreactive neurons per thousand in SHR was significantly higher in the ipsilateral lateral parabrachial nucleus (P less than 0.05) and Koelliker-Fuse nucleus (P less than 0.01) than in WKY, while it was significantly lower in the ipsilateral medial subnucleus (P less than 0.05) and the commissure subnucleus (P less than 0.05) of the nucleus tractus solitarii in SHR than in WKY. The results indicate that: (1) glutamate-immunoreactive neurons (possibly glutamatergic) in many central autonomic nuclei project into the sympathetic vasomotor control neurons in the SRF; (2) the large population of glutamate-immunoreactive neurons in the lateral parabrachial nucleus and the Koelliker-Fuse nucleus of SHR is likely to increase excitatory inputs to the SRF vasomotor control neurons, while the smaller population of glutamate-immunoreactive neurons in the medial and commissure subnuclei of the nucleus tractus solitarii is likely to decrease excitatory inputs to the GABAergic neurons intrinsic to the SRF.

Animals↗
PubMed1992

Immunosuppressive effects induced by the polysaccharide moiety of some bacterial lipopolysaccharides.

The immunomodulatory properties of several lipopolysaccharides (LPS) derived from clinical isolates of Pseudomonas aeruginosa, Branhamella catarrhalis, and Bordetella pertussis were evaluated for their capacity to influence the magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III), which is known to be regulated by suppressor and amplifier T cells (Ts and Ta, respectively). The administration of LPS, two days after immunization resulted in a significant increase in the antibody response. Such enhancement may be due mainly to the ability of the lipid A moiety of LPS to abolish the negative effects of activated Ts, thereby enabling Ta function to be more fully expressed; however, B cell mitogenicity of the LPS molecule also may be involved. By contrast, treatment with LPS at the time of immunization with SSS-III induces significant suppression of the SSS-III-specific antibody response; such suppression is not induced by LPS or lipid A derived from Escherichia coli and Salmonella minnesota, and is independent of the capacity of LPS to activate B cells polyclonally, an activity generally attributed to the lipid A fraction of LPS. Studies conducted with the LPS of P. aeruginosa indicated that the suppression induced is T cell dependent and mediated by the polysaccharide (PS) fraction of LPS; it appears to be due-at least in part-to the capacity of PS to expand or increase the size of the precursor pool of Ts, activated in response to SSS-III. The significance of these findings to the pathogenesis of certain gram-negative infections is discussed.

Animals↗
PubMed1992

Immunochemical detection of arachidonoyl-preferential phospholipase A2.

Monoclonal antibodies were raised against rabbit platelet cytosolic arachidonoyl-preferential phospholipase A2. The antibodies precipitated the arachidonoyl-preferential phospholipase A2 activity in the soluble fraction of a rabbit platelet lysate in combination with an immobilized anti-mouse immunoglobulin antibody, and reacted predominantly with a protein exhibiting a molecular weight of approximately 88,000 on immunoblotting analysis. All three antibodies established so far reacted with human platelet arachidonoyl-preferential phospholipase A2 as effectively as the rabbit platelet enzyme. One of them reacted with the rat platelet arachidonoyl-preferential enzyme, whereas none of them reacted with rabbit platelet secretory 14-kDa group II phospholipase A2. The existence of an immunologically related phospholipase A2 was further shown in rabbit granulocytes, brain, lung, and liver, rat and mouse mast cells, and human monocytoma U937 cells. Thus, an arachidonoyl-preferential phospholipase A2 with similar structural properties appeared to be expressed in a variety of cells and tissues.

Animals↗
PubMed1992

Cooperative transcription activation between Ad1, a CRE-like element, and other elements in the CYP11B gene promoter.

We previously reported the presence of six different cis-acting elements (Ad1 to Ad6) in the promoter region of the bovine CYP11B gene. Although the Ad1 site (TGACGTGA) was similar to a palindromic CRE (TGACGTCA), two other upstream sequences, Ad3 and Ad4, were identified as the cAMP response sequences of the gene. We analyzed the functional relationship between the Ad1 site and the upstream elements. Mutation analyses of the Ad1 site indicated that the 5' half of the site (TGACG) was important for the transcription of the gene in vitro. In Y-1 cells, a plasmid with a mutated Ad1 showed no response to cAMP. The effect of the mutation at the Ad1 site on the cAMP response was almost the same as that of the deletion of Ad3 and Ad4, although the role of each element seemed to be different. These results indicated that both the Ad1 site and the upstream elements, Ad3 and Ad4, were necessary for the full response to cAMP of the CYP11B gene. When the Ad1 site in the promoter region was replaced with a palindromic CRE, elevated transcription activity was detected both in vitro and in vivo. Two kinds of CREBs (43 and 47 kDa) purified from a HeLa cell nuclear extract bound to the Ad1 site. The binding of the palindromic CRE to the nuclear factor(s) was stronger than that of Ad1.

Animals↗
PubMed1992

The influence of detergents on skin barrier properties.

The influence of surfactants on the changes in skin barrier properties was investigated in rats. Various ionic and non-ionic surfactants were assessed using indomethacin as a model penetrant. The surfactants appeared to either increase or decrease the skin permeability, due to the properties of both compound and surfactant. Ionic surfactant sodium dodecylsulfate was the most powerful and exceeded controls by approximately 10 times measured by means of serum levels of indomethacin. Other surfactants caused concentration increase or decrease of indomethacin in serum.

Administration, Cutaneous↗
PubMed1992

Rhodopseudomonas sphaeroides lipid A derivatives block in vitro induction of tumor necrosis factor and endotoxin tolerance by smooth lipopolysaccharide and monophosphoryl lipid A.

Rhodopseudomonas (Rhodobacter) sphaeroides diphosphoryl lipid A is a relatively inert species of lipid A but has been shown to antagonize the effects of toxic lipopolysaccharide (LPS) both in vivo and in vitro. The antagonist and its monophosphoryl derivative were examined for the ability to block tumor necrosis factor synthesis and reverse tolerance induction in vitro in macrophage cultures stimulated with bioactive preparations of smooth LPS, rough LPS, diphosphoryl lipid A, and monophosphoryl lipid A. Inhibition of agonist activity and reversal of tolerance by these novel penta-acylated lipid A antagonists provides new insight into macrophage-LPS interactions.

Animals↗
PubMed1992

Structural features that influence the ability of lipid A and its analogs to abolish expression of suppressor T cell activity.

Lipid A preparations derived from the lipopolysaccharides of several gram-negative bacteria, as well as chemically defined synthetic lipid A's and their analogs (both glucosamine mono- and disaccharides), were used to establish the chemical structures required for (i) abolishing the expression of suppressor T cell (Ts) function and (ii) inducing polyclonal activation of B cells. Salmonella minnesota R595 lipid A (diphosphoryl lipid A) possesses both of these activities. Decreasing the number of phosphate groups in lipid A from two to one (monophosphoryl lipid A) as well as decreasing the fatty acyl content, primarily by removing the residue at the 3 position, resulted in a progressive reduction in toxicity; however, these structural modifications did not influence its ability to abolish the expression of Ts function. Reducing the fatty acyl content from five to four (lipid A precursor IVA or Ia) eliminated the capacity to influence Ts function but not to induce polyclonal activation of B cells. None of the monosaccharide analogs of lipid A examined influenced the expression of Ts activity, although some were able to activate B cells polyclonally. Thus, in order to be able to abolish the expression of Ts function, lipid A (i) must be a glucosamine disaccharide, (ii) may have either one or two phosphate groups, and (iii) must have at least five fatty acyl groups. Also, the chain length of the nonhydroxylated fatty acid, as well as the location of acyloxyacyl groups (2' versus 3' position), may play an important role. These findings indicate that the chemical structures responsible for the toxicity of lipid A differ from those that influence its capacity to abolish the expression of Ts function and to induce polyclonal activation of B cells.

Animals↗
PubMed1992

Percutaneous absorption of ketoprofen from acrylic gel patches containing d-limonene and ethanol as absorption enhancers.

The percutaneous absorption of ketoprofen (KPF) from gel patches containing d-limonene and ethanol was investigated in rats. Plasma levels of KPF varied with the kind of polymers which constitute the gel patch, and the highest level was observed when the copolymer of ethylacrylate (EA) and diethyleneglycolmethacrylate (DEGMA) was used as a vehicle. The amount of KPF permeating through the rat skin from the gel patch was well correlated with that of ethanol. Permeations were enhanced with increase in the amount of d-limonene distributed from the vehicle to the skin tissue. The amount of d-limonene accumulated in the skin varied greatly with the kind of polymers; the highest accumulation was observed with the EA-DEGMA copolymer, and decreased with increasing affinity of d-limonene to the polymers. The reason EA-DEGMA copolymer showed the highest percutaneous absorption of KPF from gel patches containing d-limonene may be the hydrophilic nature of this polymer which showed the lowest affinity to d-limonene.

Administration, Cutaneous↗
PubMed1992

Effect of d-limonene on the amounts of ethanol and indomethacin penetrated from aqueous gel ointments to rat skin.

The amounts of d-limonene, ethanol and indomethacin (IMC) which were transferred from aqueous gel ointments to the skin were determined in rats. The concentration of IMC in the skin correlated well with the plasma concentration of IMC percutaneously absorbed from the gel ointment. The increase of d-limonene concentration in the gel ointments was directly proportional to the accumulation of ethanol in the skin. The amount of ethanol in the skin was closely associated with the percutaneous absorption of IMC. As a possible mechanism for enhancement action of d-limonene and ethanol, it was considered that, at first, d-limonene penetrates into the skin under coexistence with ethanol and may change the barrier structure of the stratum corneum. The transfer of ethanol to the skin is thereby enhanced under the coexistence of d-limonene in the skin. Thus, the permeation of IMC can be promoted due to its affinity with ethanol.

Absorption↗
PubMed1992

Factors affecting prednisolone release from hydrogels prepared with water-soluble dietary fibers, xanthan and locust bean gums.

The release behavior of prednisolone from hydrogels prepared with xanthan and locust bean gums was investigated. Newly developed equipment was employed in order to increase the gum concentration in the hydrogels. The apparent release rate of prednisolone from the hydrogels decreased with increasing gum concentration, suggesting that the diffusion of drug molecules was mainly controlled by the density of the three-dimensional network structure in the matrix. The effect of additives such as glycerin and sucrose on the release behavior of prednisolone was also investigated in detail. Drug release was significantly lowered by the addition of these compounds to these hydrogels. A linear relation was observed between the apparent release rate of prednisolone and microscopic viscosity of the hydrogels. These results indicated that the drug release could be controlled not only by the density of the network structure but also by the microscopic viscosity of the hydrogels.

Delayed-Action Preparations↗
PubMed1992

The usefulness of step sectioning of transbronchial lung biopsy specimen in diagnosing sarcoidosis.

To evaluate the usefulness of step sectioning of the transbronchial lung biopsy (TBLB) specimens obtained from patients with suspected sarcoidosis, we examined all TBLB specimens obtained from 132 patients who were diagnosed clinically as having sarcoidosis at our institute. When routine sections of TBLB specimens did not show sarcoid granuloma, we prepared additional serial sections from each block and stained every fifth section with hematoxylineosin (step sectioning). All step sections were examined histologically. With the aid of step sectioning, the diagnostic yield of sarcoidosis increased from 38 percent (18/47) to 47 percent (22/47) in stage 1 patients, and from 57 percent (37/65) to 82 percent (53/65) in stage 2 patients. All of the newly detected granulomas were identified between the first and seventh sections. We conclude that step sectioning is useful method in diagnosing sarcoidosis.

Aged↗
PubMed1992

Influence of limonene and laurocapram on percutaneous absorption of nonsteroidal anti-inflammatory drugs.

The promoting effect of cyclic monoterpenes, 1% limonene (CAS 5989-27-5) and 1% cineole (CAS 470-82-6), on percutaneous absorption of nonsteroidal anti-inflammatory drugs was investigated in the rats. Compared with 1% laurocapram, drug absorption from the gel ointments was significantly more enhanced by addition of 1% limonene, while without any enhancer only ibuprofen penetrated across the skin in the limited amount. When using formulation with propylene glycol or 50% propylene glycolethanol solution, instead of carboxyvinyl polymer gel, percutaneous absorption significantly decreased and neither limonene nor cineole or laurocapram were capale to promote percutaneous absorption of flufenamic acid to sufficient serum level. Cineole and limonene were also evaluated in permeation experiments in vitro. Enhancement ability of limonene in the gel oinment was approximately 5 times higher comparing with enhancement ratio of cineole, while in 100% propylene glycol enhancement ability of both cyclic monoterpenes was equal. Good correlation was observed between in vivo and in vitro experiments. Evaluation of solubility proved that in the gel ointment simulated as water-ethanol solution were relatively best condition for percutaneous absorption of flufenamic acid when comparing with propylene glycol or 50% propylene glycol-ethanol solution.

Administration, Topical↗
PubMed1991

Glutamate-immunoreactive neurons of the central amygdaloid nucleus projecting to the subretrofacial nucleus of SHR and WKY rats: a double-labeling study.

Glutamate immunoreactivity was found in 9%, in the case of Wistar Kyoto rats (WKY), and 14%, in the case of spontaneously hypertensive rats (SHR), of neurons located in the medial division of the central amygdaloid nucleus (CeM) projecting ipsilaterally to the subretrofacial nucleus (SRF) in the rostral ventrolateral medulla using a double-labeling technique in combination with glutamate immunocytochemistry. The results indicate that possibly-glutamatergic neurons located in the CeM project to the SRF, in which vasomotor neurons are present, suggesting involvement of the CeM in blood pressure regulation. No significant difference was found between the distribution of labeled CeM neurons in SHR and WKY rats.

Afferent Pathways↗
PubMed1991

Lipid A-like molecules that antagonize the effects of endotoxins on human monocytes.

Lipopolysaccharide (LPS) endotoxin is implicated as the bacterial product responsible for the clinical syndrome of Gram-negative septicemia. Although the lipid A domain of LPS appears to be responsible for the toxicity of endotoxin, lipid A from the photosynthetic bacterium Rhodobacter sphaeroides (RSLA) and a disaccharide precursor of lipid A from enteric bacteria, termed lipid IVA, have little activity on human cells. Using the human promonomyelocytic cell line THP-1 and human monocytic cells, we now show that both lipid IVA and RSLA are antagonists of LPS. Complete, apparently competitive, inhibition of LPS activity is possible at a 10-100-fold excess of antagonist, as judged by measuring the release of cytokines and prostaglandin E2. Both antagonists prevent monocyte stimulation by endotoxin extracted from a variety of Gram-negative bacteria. Cells pretreated with either inhibitor and subsequently washed still show attenuated responses to LPS. Stimulation of monocytes by whole Gram-negative bacteria is also antagonized in a dose-dependent manner. Lipid X has no inhibitory effect in the same dose range as lipid IVA and RSLA. These findings rule out LPS sequestration as the explanation for the observed antagonism. Neither inhibitor alters monocyte stimulation by phorbol 12-myristate 13-acetate, Staphylococcus aureus, or purified protein derivative, demonstrating specificity for LPS. Although RSLA appears to inhibit LPS when tested with macrophages from both humans and mice, lipid IVA had the unique ability to act as an LPS antagonist with human-derived cells but to exhibit LPS-like effects with murine-derived cells. Like LPS, lipid IVA stimulated the release of both tumor necrosis factor alpha and arachidonic acid from murine-derived RAW 264.7 macrophage tumor cells. The range of concentrations necessary for lipid IVA to induce LPS-like effects in murine cells was similar to that necessary to antagonize the actions of LPS in human monocytes. The agonist activities of lipid IVA were completely inhibitable by RSLA. This unique species-dependent pharmacology observed with lipid IVA may reflect differences between human and murine LPS receptors. RSLA and lipid IVA may be useful in defining the role of LPS in Gram-negative bacterial infections and may prove to be prototypical therapeutic agents for the treatment of Gram-negative septicemia.

Animals↗
PubMed1991

An improved synthesis of trehalose 6-mono- and 6,6'-di-corynomycolates and related esters.

A simplified synthesis of 6-mono- and 6,6'-di-corynomycolate esters of alpha,alpha-trehalose, and related compounds, was achieved by coupling the (hydroxyl-protected) acids to the partially trimethylsilylated sugar in the presence of dicyclohexylcarbodiimide and 4-dimethylaminopyridine. As acid reactants, (2-RS,3-RS)-3-hydroxy-2-tetradecyloctadecanoic acid (DL-corynomycolic acid) and its 2RS,3SR diastereomer were prepared from methyl palmitate by sequential Claisen condensation, reduction, chromatographic separation, and saponification. Reaction with tert-butylchlorodimethylsilane (imidazole) gave the disubstituted ether-esters, which were converted into the required 3-tert-butyldimethylsilyl ethers by partial hydrolysis. 6-Linked monocorynomycolate was obtained in excellent yield (78%) from the reaction of the RS,SR acid with the known heptakis-O-(trimethylsilyl)trehalose, and in good yield from equimolar portions of RS,RS acid and hexakis-O-(trimethylsilyl)trehalose. An excess (2.5-molar portions) of the RS,RS acid gave the 6,6'-diester (69%). The mono- and di-palmitate were similarly obtained from (Me3Si)6-trehalose. The mono (RS,RS)-(Me3Si)6-trehalose coupling product was partially resolved on a silica gel column into its RR and SS diastereomers, the former corresponding to the naturally occurring trehalose monocorynomycolate. All coupling products were deprotected to free trehalose esters by treatment first with K2CO3 in methanol, then tetrabutylammonium fluoride-trifluoracetic acid in oxolane.

Carbohydrate Sequence↗
PubMed1991

Detection of 14-kDa group II phospholipase A2 in human seminal plasma.

About 90% of phospholipase A2 activity detected in human seminal plasma reacted with monoclonal antibodies raised against human synovial fluid phospholipase A2. The crude seminal plasma yielded a pure immuno-cross-reactive phospholipase A2 preparation in a single purification step using immuno-affinity chromatography. The amino acid sequence of the N-terminal 20 residues of this seminal enzyme was determined and found to be identical with that of human synovial phospholipase A2. Thus, it is suggested that human seminal plasma contains phospholipase A2, belonging to the 14-kDa group II enzyme family, as the major isoenzyme.

Amino Acid Sequence↗