[The accessory cell function of human alveolar macrophages in antigen-induced T-lymphocyte proliferative responses].
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Biomedical subjects
Publications and source records attributed to K Fukuda.
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The antiemetic efficacy of high-dose metoclopramide (MCP), diphenhydramine (DPH), methylprednisolone (MPL), and diazepam (DZP) was investigated in 40 gynecologic cancer patients for a total of 98 chemotherapy courses, treated with cisplatin (50 mg/m2). With MPL (500 mg i.v. x 2) plus DZP (5 mg i.m. x 2), no vomiting occurred in 0% and mild emesis (vomiting 1-2 times) occurred in 20% of 25 courses. With MCP (2 mg/kg i.v. x 5) plus DPH (40 mg i.v. x 3), no vomiting occurred in 35% and mild emesis occurred in 10% of 20 courses. With a combination of MCP plus DPH and MPL plus DZP, no vomiting occurred in 51% and mild emesis occurred in 25% of 53 courses. These results indicate that high-dose MCP plus DPH are effective in preventing cisplatin-induced vomiting. Furthermore, the antiemetic efficacy of MCP plus DPH (0-2 vomiting episodes: 45%) was significantly enhanced (p less than 0.05) by the combined use of MPL plus DZP (0-2 vomiting episodes: 76%).
Although atrial natriuretic peptide (ANP) has recently been verified to function as a neuropeptide in the central nervous system, its definite identification has not been done so far. We have isolated two ANP-related peptides from porcine brain by utilizing alpha-ANP specific radiommunoassay coupled with immunoaffinity chromatography and reverse phase HPLC. By structural analyses, these two peptides were determined to be alpha-ANP [4-28] and alpha-ANP [5-28]. They were found to elicit chick rectum relaxant activity comparable to alpha-ANP. These results indicate that proteolytic processing of ANP precursor in the central nervous system takes place in a manner different from that in heart and plasma, where gamma-ANP and alpha-ANP are known to be the main components of ANP, respectively.
We have developed an enzyme-linked immunosorbent assay (ELISA) for the quantitation of C3 nephritic factor of the alternative pathway of complement (NeFA). Incubation of the NeFA-positive serum (patient KS serum) with normal human serum (NHS) in Mg-EGTA resulted in the formation of C3-B-IgG complex. No complex was formed in EDTA. At first this was detected as three types of complexes: C3-IgG, B-IgG and B-C3, by the combination of antibodies. The reaction mixture in Mg-EGTA was filtered through an ACA 22 column, from which the complexes were eluted in the same part as the first protein peak. When IgG purified from KS serum was incubated with NHS in Mg-EGTA, B-C3 complex increased in proportion to the dose of IgG. These results indicated that only one kind of complex consisting of IgG, C3 and B (IgG-C3-B) was generated by the addition of NeFA to NHS. Serum NeFA could be quantified as the titer of B-C3 complex formed after its incubation with NHS in Mg-EGTA. Using the ELISA method, NeFA was positive in five out of six patients with membranoproliferative glomerulonephritis (MPGN) type II and in only one of 17 with MPGN type I. Titers obtained by the new method were in good accordance with those by C3 conversion and C3bBb stabilization assays for NeFA, and the new method was more exact and simple than the conventional methods.
Two glycoproteins (apparent molecular weights 120,000 and 70,000) were extracted from rabbit erythrocyte membranes, and only one (Mr 120,000), which is a sialoglycoprotein, contained O-glycosidically linked sugar chains. Alkali-labile oligosaccharide units of the sialoglycoprotein were released as reduced oligosaccharides by NaOH-NaB3H4 treatment, and then purified by gel filtration on a Bio-Gel P-4 column followed by ion-exchange chromatography. From the results of methylation analysis, mass spectrometry and chromium trioxide oxidation, the main oligosaccharide unit was determined to be a linear trisaccharide (85% by weight), NeuNGc alpha(2----3)Gal beta(1----3)GalNAcol. In addition, small amounts of a tetrasaccharide (11% by weight) and a disaccharide (4% by weight) were found, which were determined to have the following structures, NeuNGc alpha(2----3)Gal beta(1----3)[NeuNGc alpha(2----6)] GalNAcol and Gal-GalNAcol, respectively.
Mutants of the Torpedo nicotinic acetylcholine receptor in which each of the putative transmembrane segments of the alpha-subunit is replaced by the hydrophobic transmembrane segment of the vesicular stomatitis virus glycoprotein or of the human interleukin-2 receptor have been produced in Xenopus oocytes by cDNA manipulations. Functional analysis of these mutants shows that the hydrophobic segment M4 can be replaced by foreign transmembrane sequences without loss of channel activity. It is also suggested that the hydrophobic segments M1, M2 and M3 and the amphipathic segment MA are important for efficient expression of the acetylcholine receptor on the cell surface and that the specific amino acid sequence of segment M2 may be involved in channel activity.
Kinetic study of the reaction between vitamin E radical and vitamin C has been performed. The rates of reaction of vitamin C (ascorbic acid 1, 6-0-stearyl ascorbic acid 2, and 2,6-O-dipalmitoyl ascorbic acid 3) with vitamin E radical (5,7-diisopropyl-tocopheroxyl) in benzene-ethanol (2:1, v/v) solution have been determined spectrophotometrically, using stopped-flow technique. The second-order rate constants obtained are 549 +/- 30 M-1s-1 for 1, 626 +/- 53 M-1s-1 for 2, and 4.84 +/- 1.41 M-1s-1 for 3 at 25.0 degrees C. The result shows that the ascorbic acid ester 2 having a long-alkyl-chain at 6-position is 1.14 times as reactive as the ascorbic acid 1, whereas the ascorbic acid ester 3 substituted at 2-position is only 0.01 times as reactive as the ascorbic acid 1.
The interaction of the specific sugar residue in ginsenosides with egg phosphatidylcholine vesicles was investigated by ESR spectrometry using phosphatidic acid spin-labeled at the polar head groups. Ginsenoside-Rc, which has an alpha-L-arabinofuranose residue and agglutinability toward egg yolk phosphatidylcholine vesicles (Fukuda, K. et al. (1985) Biochim. Biophys. Acta 820, 199-206), caused the restriction of the segmental motion of spin-labeled phosphatidic acid in egg phosphatidylcholine vesicles, indicating that the saponin interacted with the polar head groups of vesicles. Other ginsenosides-Rb2, Rb1, Rd and p-nitrophenyl glycoside derivatives which have less or no agglutinability were also investigated in the same manner. Only ginsenoside-Rb2 and p-nitrophenyl alpha-L-arabinofuranoside which have the specific sugar residue (arabinose) showed a strong interaction with the polar head groups of vesicles. To gain an insight into the mechanism of agglutination by ginsenoside-Rc, the interaction with the fatty acyl groups was also studied by using phosphatidylcholine spin-labeled at the fatty acyl groups. Ginsenoside-Rc increased the order parameter of the spin-labeled phosphatidylcholine, indicating that the saponin was inserted into lipid bilayers. In other saponins investigated, only ginsenoside-Rb2 interacted with the fatty acyl part of vesicles. The process of expression of agglutination by ginsenoside-Rc was discussed on the basis of the ESR studies.
The four kinds of subunits of the Torpedo californica nicotinic acetylcholine receptor have been produced in various combinations by injecting Xenopus oocytes with the corresponding subunit-specific mRNAs synthesized by transcription in vitro of the cloned cDNAs. Functional analysis suggests that association of the alpha-subunit with either the gamma- or the delta-subunit is a prerequisite for generating the conformation necessary for agonist binding. The acetylcholine receptor devoid of either the beta-, gamma- or delta-subunit exhibits weak channel activity.
A highly sensitive and rapid liquid chromatographic method for the determination of free and total phenylacetic and p- and m-hydroxyphenylacetic acids in human urine is described. After extraction of urine with diethyl ether, these acids and phenylpropionic acid (internal standard) are converted into the corresponding fluorescent derivatives by treatment with 3-bromomethyl-6,7-dimethoxy-1-methyl-2(1H)-quinoxalinone in the presence of potassium hydrogen carbonate and 18-crown-6 in acetonitrile. The derivatives are separated on a reversed-phase column (Radial-Pak cartridge C18) with aqueous 65% (v/v) methanol and detected fluorimetrically. The detection limits for phenylacetic and p- and m-hydroxyphenylacetic acids are 5, 30 and 100 fmol, respectively, at a signal-to-noise ratio of 5 in a 20-microliter injection volume. This sensitivity permits precise determination of the free and total acids in 20 microliter of normal human urine.
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The effects of the monoclonal antibody-mitomycin C conjugate against human colon cancers were studied, in vitro and in vivo. Mitomycin C (MMC) was conjugated with the human colon cancer-specific monoclonal antibody, using a cyanogen bromide method. The effect of the conjugate and free MMC, in vitro, was measured by incubation with human colon cancer SW1116 cells. The MMC concentration of the conjugate and of free MMC needed for 50 per cent killing of target cells was 0.11 microgram/ml and 7.00 micrograms/ml, respectively. The effect of the conjugate and of free MMC, in vivo, was assayed by the growth inhibition of human colon cancer xenografted in nude mice, after intraperitoneal injections of 30 micrograms MMC/kg. Antitumor effects of the conjugate against the cancer in nude mice were significantly more potent than that of free MMC.
Among about 1000 male college students, 6 short and 5 long sleepers were finally selected on the basis of their responses to a sleep habit questionnaire. The subjects slept in the laboratory for 6 consecutive nights. On nights 4, 5 and 6, deliberate sleep interruption was performed during the second sleep cycle. During interruption, subjects were asked to perform 3 different kinds of tasks on each of the 3 nights. Stage REM latencies after interruption were distributed bimodally with peaks at sleep onset after the interruption (sleep onset REM period: SOREMP) and 50-60 min later (non-SOREMP). SOREMPs were observed only in the sleep of short sleepers. Short sleepers showed a shorter sleep latency and a greater amount of stage REM in the 2nd and the 3rd sleep cycle of their baseline sleep record than did long sleepers. These characteristics of short sleepers' sleep and sleep interruptions probably affected the occurrence of SOREMPs. The mean duration of SOREMPs was significantly shorter than that of non-SOREMPs.
After recognizing that moth, butterfly, caddis fly, and chironomid were the insects predominantly found in our environment, reaginic sensitivities to these insects in patients with asthma were investigated with extracts of silkworm wing for the detection of moth and/or butterfly allergy, caddis fly wing for caddis fly allergy, and chironomid whole body for chironomid allergy. At least 50% of 56 randomly selected patients with asthma had positive intracutaneous reactions to these insect extracts, and at least 80% of the skin reaction positive patients had specific IgE antibodies. An immunochemical assay of these insect-related aeroallergens in the dust collected 18.6 m above ground revealed the presence in the air of insect-related particles less than 10 microns in diameter with two peaks a year, one in the spring (silkworm wing, 3.18 ng protein equivalent to that of the crude extract per cubic meter of air; caddis fly wing, 3.08 ng/m3; and chironomid whole body, 5.21 ng/m3) and one in the autumn (silkworm wing, 8.24 ng/m3; caddis fly wing, 4.74 ng/m3; and chironomid whole body, 18.19 ng/m3). Although we have no idea whether or not such peak values are enough to cause asthmatic symptoms, seasonal fluctuations of specific IgE antibodies to these insects appeared to be similar to those of atmospheric insect allergens measured by this method. These findings suggest that insects are widespread and common inhalant allergens.
Our previous experiment showed that the sensitivity of striatal dopaminergic metabolism to apomorphine was lowered after pretreating rats with methamphetamine. This study further demonstrated that haloperidol administered with methamphetamine prevented the effect of the methamphetamine pretreatment. Since gamma-butyrolactone was administered in combination with apomorphine so as to remove complications which might arise from the modification of impulse flow through the striatonigral feedback loop, it is possible that the observed effect of apomorphine upon striatal dopaminergic metabolism and its antagonism with haloperidol may be mediated by autoreceptors of dopaminergic axon terminals in rat striatum.
We reported the results of a survey of patients who suffered from schizophrenia with predominate hallucinatory and delusional states, and who had been unresponsive to a variety of antipsychotics like haloperidol but responded more favorably to zotepine. In 10 of the 22 zotepine-responsive patients in this study, there was marked improvement with zotepine. Considering the results from previous drug treatment, the phenothiazines (especially levomepromazine) surpassed the butyrophenones in efficacy, suggesting that zotepine might resemble levomepromazine clinically. After administration of zotepine, cenesthesic hallucination, behavior caused by hallucination, egorrhoe, affective symptoms, and catatonic symptoms were markedly improved. However, insight into disease and negative symptoms were minimally improved after administration of zotepine. Zotepine was effective in the refractory psychoses due to its potent action on the delusional dynamics, in spite of producing little marked improvement in such main symptoms as hallucination and delusion. The authors speculate that zotepine's potent activity at serotonin-1 receptors may lead to a beneficial effect in refractory psychoses, just as in the case of its antimanic effect.