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Biomedical subjects

K Ichikawa

Publications and source records attributed to K Ichikawa.

At least 343 records · Page 19Linked to original sources

A model for open-close control of cation channels in the plasma membrane of retinal rod outer segments.

A model for open-close control of cation channels in the plasma membrane of retinal rod outer segments is presented. A channel is assumed to open when 3 cGMP molecules bind to it and close as soon as one of the 3 cGMP molecules is released from it. The calcium ion (divalent cation) is a modulator of the channel conductance. The channel conductance is low when Ca2+ binds to it, while it is high when it is free from Ca2+. From the above assumptions, the reaction scheme of channels with cGMP and Ca2+ is created and the fraction of channels in the open and closed states was calculated using equations for this scheme. The kinetic constants used in the model are estimated from the experimental results of many studies and from the theories. From this estimation, it was found that at the physiological concentrations of intracellular and extracellular Ca2+, almost all channels are bound with Ca2+ and are in the low conductance state. The present model accounts for the reported dose(cGMP)-response(membrane current or conductance) relationship, where the Hill coefficient decreases as the cGMP concentration increases. The dark-level cGMP concentration of 8.13 microM is estimated from the model. This is in good agreement with the reported values. Moreover, the model predicts the invariance of current noise at relatively low Ca2+ concentrations when the cGMP concentration is raised from the dark level to a saturation level. The dynamic properties (opening and closing actions) of the channels in the present model are also in good agreement with the reported observations. The burst mode opening and closing of a channel is predicted by the present model, and it was found that the number of openings in a burst is controlled by the forward and backward rate constants between a channel protein and cGMP molecules. The simulated waveform of a single channel is similar to the reported observations.

Calcium Channels↗

IgG class anti-cardiolipin antibody as a possible marker for evaluating fetal risk in patients with systemic lupus erythematosus.

To identify the correlation between incidence of anti-phospholipid antibodies and fetal prognosis in pregnant SLE patients, we measured the amount of anti-cardiolipin antibody in their sera, using solid-phase enzyme immunoassay (EIA) methods. Findings in the group having poor obstetric results (fetal loss group) and in those with a history of full-term births (live birth group) were compared with regard to other anti-phospholipid antibodies. The incidence of IgG class anti-cardiolipin antibody was 60% in the fetal loss group and 19% in the live birth group, (P less than 0.05). The incidence of the other anti-phospholipid antibodies, including lupus anticoagulant and biological false-positive serological test for syphilis (BFP-STS), did not differ significantly between the two groups. Therefore, the presence of IgG class anti-cardiolipin antibody may prove to be a useful marker for evaluating fetal risk in SLE patients.

Biomarkers↗

ECF pH dynamics within the ventrolateral medulla: a microelectrode study.

Using pH-sensitive microelectrodes, we evaluated pH dynamics of extracellular fluid (ECF) within the ventrolateral medulla (VLM) beneath the central chemoceptive areas in anesthetized, spontaneously breathing cats. Static ECF pH was acid in the superficial layers (less than 1 mm), compared with the overlying cerebrospinal fluid pH that became alkaline gradually during the experiments. In the deeper VLM areas (1-3 mm), no systematic gradients of ECF pH were observed. We found various, isolated regions where intravertebral artery injections of CO2-saturated saline evoked acidic shift of ECF pH in the time course analogous to ventilatory augmentation. Those responsive regions were found to be scattered not only in the superficial layers but also in the deeper VLM areas, although many nonresponsive regions were also intermingled among them. Occlusions of the principal vessels supplying the tested VLM regions diminished but failed to abolish the ECF pH responses to the CO2 loadings, suggesting a collateral blood flow by fine pial vessels. The present study suggests a possibility that the pH-dependent central chemoreceptors, if any, would be scattered in the deeper VLM areas as well as the superficial layers.

Animals↗

Counterregulation of nuclear 3,5,3'-triiodo-L-thyronine (T3) binding by oxidized and reduced-nicotinamide adenine dinucleotide phosphates in the presence of cytosolic T3-binding protein in vitro.

The role of cytosolic T3-binding protein (CTBP) in the regulation of nuclear T3 binding was studied in vitro. Nuclear [125I]T3 binding was observed in the presence of 1.0 mM dithiothreitol (DTT). When the nuclei prepared from rat kidney were incubated with inactive form of CTBP which was also prepared from rat kidney, [125I]T3 binding to nuclei was not affected. When the nuclei were incubated with inactive form of CTBP in the presence of NADP, [125I]T3 binding to nuclei was increased, whereas binding was diminished when nuclei were incubated with CTBP in the presence of NADPH. The inactive form of CTBP was activated by NADPH. NADP also activated CTBP in the presence of DTT. Both active forms of CTBP were again inactivated by extraction with charcoal, and these inactive forms were reactivated by NADPH or by NADP and DTT, but not by NADP alone. Although the nuclei treated with 0.3 M NaCl lost the binding activity for [125I]T3 in the absence of NADP, the nuclei retained the binding activity for [125I]T3 in the presence of NADP and the inactive form of CTBP. Treatment of the nuclei with 0.5 M NaCl lost the binding activity for [125I]T3 not only in the absence but also in the presence of NADP and CTBP. These results suggested that NADP and NADPH play roles as counterregulatory factors for nuclear T3 binding in the presence of CTBP. Further, it was speculated that binding sites for the T3-CTBP complex, which is generated in the presence of NADP and DTT, are present in nuclei, and that binding sites for the complex are different from nuclear T3 receptors.

Animals↗

Cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) regulation of nuclear T3 binding: evidence for the presence of T3-CTBP complex-binding sites in nuclei.

Effect of cytosolic 3,5,3'-triiodo-L-thyronine (T3)-binding protein (CTBP) on [125I]T3 binding to nuclei was investigated in vitro. CTBP and nuclei were prepared from rat kidney. CTBP was inactivated by incubating with charcoal and activated by incubating with NADPH or with NADP and dithiothreitol. Two complexes of CTBP and T3 [CTBP-T3(NADPH) and CTBP-T3(NADP)] were separately prepared, and the functions of these complexes were estimated. [125I]T3 binding to nuclei was not influenced by the inactive form of CTBP. NADP or NADPH alone did not modify [125I]T3 binding to the nuclei. However, the binding was markedly inhibited by NADPH in the presence of the inactive form of CTBP, but it was not inhibited by NADP in the presence of the inactive form of CTBP. The ability of nuclei to bind [125I]T3 was markedly diminished by pretreatment of the nuclei with 10(-8) M unlabeled T3. The diminished activity was not modified by adding NADPH or NADP. However, [125I]T3 bound to these nuclei in the presence of NADP and the inactive form of CTBP. Binding of [125I]T3 to these nuclei was not observed in the presence of NADPH and the inactive form of CTBP. When the nuclei that had previously been saturated with 10(-6) M unlabeled T3 were incubated with [125I]T3-CTBP(NADP) complex, radioactivity bound to the nuclei. The binding of radioactivity, however, was not observed when these nuclei were incubated with [125I]T3. The [125I]T3-CTBP(NADPH) complex did not bind to these nuclei. When the nuclei that had previously been treated with T3-CTBP(NADP) complex were incubated with [125I]T3, radioactivity bound to the nuclei. The binding of radioactivity, however, was not observed when these nuclei were incubated with [125I] T3-CTBP(NADP) complex. The [125I]T3-CTBP(NADPH) complex did not bind to these nuclei. These results suggested that 1) CTBP activated by NADP plays a role as a carrier protein for T3 from cytoplasm to nucleus; 2) there are binding sites for T3-CTBP(NADP) complex in rat kidney nuclei; and 3) these binding sites are different from nuclear T3 receptors.

Animals↗

The screening of Chinese crude drugs for Ca2+ antagonist activity: identification of active principles from the aerial part of Pogostemon cablin and the fruits of Prunus mume.

Hot aqueous extracts of 134 Chinese crude drugs were subjected to screening for inhibitory activity on K+ contracture of guinea pig taenia coli, and significant activity was observed in 17 crude drugs. Chemical investigations of two crude drugs, Kakko and Ubai, which originate from Pogostemon cablin and Prunus mume, respectively, were undertaken, and patchouli alcohol (I) and 5-(hydroxymethyl)-2-furaldehyde (II) were identified as their active principles, respectively.

Animals↗

[Pharmacological studies of a non-steroidal analgesic and antipyretic drug of LFP83].

Pharmacological properties of LFP83, a non-steroidal analgesic and antipyretic drug, were studied in mice, rats and rabbits. LFP83 is a prodrug of flurbiprofen (FP) which is its active major metabolite in vivo. In experimental models of acetic acid writhing, the Randall and Selitto method, arthritic pain, yeast fever, LPS fever, carrageenin edema and adjuvant arthritis, LFP83 (i.v.) showed remarkable analgesic, antipyretic and antiinflammatory activities; and it was more potent than ketoprofen (i.m.) and aspirin DL-lysine (i.v.). The analgesic activity of LFP83 was equal to or more potent than that of pentazocine, and its duration was longer than those of aspirin DL-lysine and pentazocine. In addition, the analgesic potency of LFP83 was approximately the same or more potent than that of FP (p.o.), and the onset of this analgesic effect began earlier. On the other hand, the ulcerogenic activity of LFP83 on rat gastric mucosa was less than that of FP (p.o.) in both single and consecutive (7 days) administrations. The safety index (UD50/ED50) of LFP83 was three to ten-fold higher than that of FP (p.o.). As mentioned above, LFP83 is a potent analgesic, antipyretic and antiinflammatory drug; and in comparison to oral FP, it has a more potent and immediate effect, weak gastric irritation and high safety index.

Analgesics↗

[Effects of antiinflammatory agents on rat paw tuberculin response].

A marked tuberculin response as well as carrageenin edema were induced in rat hind paw to compare the effects of antiinflammatory agents on these responses. Non-steroidal antiinflammatory agents such as diclofenac and piroxicam were very weak inhibitors of the paw tuberculin response. These agents showed only a slight inhibitory effect on tuberculin response even at doses that were four to five times larger than the 50% effective doses for inhibiting carrageenin edema. On the other hand, steroidal antiinflammatory agents, dexamethasone and prednisolone, showed potent inhibitory effects on the paw tuberculin response at the 50% effective doses for inhibiting carrageenin edema. The above findings clearly revealed the difference in characters between non-steroids and steroids by comparing their effects on tuberculin response and carrageenin edema. The different properties of two classes of antiinflammatory drugs may be of significance in evaluating the effect of antiinflammatory agents on delayed-type hypersensitivity.

Animals↗

Stabilization, accurate determination, and purification of rat liver nuclear thyroid hormone receptor.

Rat liver nuclear thyroid hormone receptor lost 3.5.3'-tri-iodo-L-thyronine (T3)-binding activity with a half-life of 14 days, 4h, 139 min, 62 min, 16 min or 6 min at 0, 36, 38, 40, 43 or 45 degrees C respectively, when present in crude nuclear extracts. Glycerol increased the half-life of the receptor during heat inactivation. Protection was reversible by removing the glycerol. The receptor was unstable at a pH below 6.0 or above 10.0. We also found a loss of the receptor activity during the separation of bound and free hormone using the resin test. Of several conditions tested for the separation of bound and free hormone, the addition of heated nuclear extract gave the most accurate estimation of bound hormone when using the resin test. Using these characteristics of the receptor, we purified the receptor to 1220 pmol T3-binding capacity/mg protein with a final yield of 14.6 micrograms/4 kg rat liver.

Animals↗

Possible role of histones in the organization of rat liver thyroid hormone receptors in chromatin.

The effects of histone subfractions on rat liver thyroid hormone receptor-DNA interaction were examined using an in-vitro DNA-cellulose binding assay. H1 histones bound to DNA showed reversible and potent inhibition of receptor-DNA binding without affecting receptor hormone binding. Poly-lysine, bovine serum albumin, ovalbumin and cytochrome c did not alter receptor-DNA binding. H1 histone subfractions (calf thymus lysine-rich histone (CTL)-1, CTL-2 and CTL-3) showed potent inhibition of receptor-DNA binding indistinguishable from each other. The quantity of H1 histone subfractions bound to DNA was the same. Although each subfraction has different functional properties, inhibition of receptor-DNA binding was a common feature of all the H1 histone subfractions, which is important for the non-random distribution of the receptor in chromatin. Binding of the receptor to core histones was investigated; it was found to bind to core histones more potently than to other proteins (H1 histone, ovalbumin and cytochrome c). Among core histone subfractions, H4 histone bound to the receptor most potently and is the candidate to be one of the acceptor sites of the receptor in chromatin.

Animals↗

Changes in cytosolic 3,5,3'-tri-iodo-L-thyronine (T3) binding activity during administration of L-thyroxine to thyroidectomized rats: cytosolic T3-binding protein and its activator act as intracellular regulators for nuclear T3 binding.

Changes in the amount of cytosolic 3,5,3'-tri-iodo-L-thyronine (T3)-binding protein (CTBP) and its activator during administration of L-thyroxine (T4) to thyroidectomized rats were investigated. Thyroidectomy decreased the amount of CTBP in the kidney, whereas the activator was not significantly modified by thyroidectomy. The activator was increased by administration of T4 to thyroidectomized rats. The amount of CTBP was also increased by administration of T4. The activator increased the maximal binding capacity (MBC) without changes in the affinity constant for T3 binding in CTBP. A T4-induced increase in MBC in cytosol inhibited nuclear T3 binding in vitro by competition of T3 binding between CTBP and the nuclear receptor. These results suggest that thyroid hormone increases the capacity for cytosolic T3 binding through increasing the amount of CTBP and its activator, and that these increases play a role in regulating the amount of T3 that binds to its nuclear receptor.

Animals↗

[Statistical investigation on orthodontic patients who received treatment at Fukuoka Dental College during 15 years].

It has been fifteen years since the Department of Orthodontics started in 1973, and this report concerns mainly the results of clinical observations during these period. The results were as follows: 1) Three thousand four hundred and three patients visited during a fifteen years period and 2,065 (61%) of them received orthodontic treatment. This statistical investigation was performed on 2,065 patients. 2) The numbers of treated patients increased from 1973 to 1983 without 1980 but have almost unchanged with about 180 patients from 1984 to 1987. 3) The male patients were less than the female by the ratio of 1:1.67. As to age, the patients from 6 to 12 years old accounted for 72% of all the treated. 4) Analyzed by dental age categories, patients at the stage of III A and III B comprised 54% of all the treated. 5) Analyzed by month, the patients visited on March, July and August in spring and summer vacations. 6) Most of the patients (92%) lived in Fukuoka Prefecture and 38% of them lived in Sawara-ku, where lay in the south-western part of Fukuoka city. 7) Fifty six per cent of all patients were introduced by doctors and dentists. 8) As to malocclutions, the number of mandibular protrusion was the largest, crowding case was next, and maxillary protrusion was third. The total sum of these three cases accounted for 78% of all the treated. 9) In the initial orthodontic appliances, the use of the multi-brackets appliances was first, the chin cap appliances was second and plate appliances was third. The total sum of these three appliances accounted for about 73%. 10) Analyzing to age and initial orthodontic appliances, plate, chin cap, F. K. O. and I. M. A. appliances were used at the age from 7 to 8. Lingual arch appliances were also used at the age of 8. The multi-brackets appliances increased remarkably during the recent five year period and were used at the age of 10 to 11 and over 20 years.

Adolescent↗

[Study on the effect of disodium cromoglycate (DSCG) on antigen induced IL-2 responsiveness].

We tested the effects of disodium cromoglycate (DSCG) on antigen-induced IL-2 responsiveness in lymphocytes from patients with atopic dermatitis and/or bronchial asthma. Patient lymphocytes pretreated with 5 x 10(3) micrograms/ml DSCG for 24 or 48 hours failed to induce the responsiveness to IL-2 on stimulation with Dermatophagoides farinae (Df) or ovalbumin (OVA) antigen. DSCG-treated adherent cells were blocked to present the antigen to nonadherent responding cells for induction of IL-2 responsiveness. In contrast, DSCG-treated non-adherent cells, recombined with antigen-activated adherent cells, acquired IL-2 responsiveness. However, Con A-activated lymphocytes from the same patients were not affected by the same treatment. The results indicate that DSCG is capable of suppressing antigen-induced IL-2 responsiveness but not the response induced by mitogen such as Con A.

Antigens↗

The role of suppressive macrophages in influenza virus-induced immunosuppression.

To confirm the role of macrophages in influenza virus (IV)-induced immunosuppression (IS) of mice, silica, a selectively destructive agent for macrophages, was tested for its ability to influence the IV-induced IS. Silica completely abolished that effect. In contrast, Indomethacin--a prostaglandin inhibitor--did not influence the IV-induced IS. Peritoneal macrophages of mice infected with IV were suppressive for plaque forming cell (PFC) response of normal spleen cells in vitro. The assumption was made that suppressive macrophages were induced by IV in mice. However, no suppressive factors were found in the culture fluid of these cells.

Animals↗