Biomedical subjects

H Yagi

Publications and source records attributed to H Yagi.

At least 19 recordsLinked to original sources

PubMed1992

Mutagenic specificities of four stereoisomeric benzo[c]phenanthrene dihydrodiol epoxides.

The pS189 shuttle vector carrying a supF target gene was used to compare the mutagenic specificities of the four configurational isomers of benzo[c]phenanthrene 3,4-dihydrodiol 1,2-epoxide. One of these isomers is the most tumorigenic dihydrodiol epoxide tested to date and another is essentially inactive as a tumorigen. Overall mutagenicities were not correlated with tumorigenicities, but each configurational isomer induced a unique spectrum of mutational hot spots in the supF target gene, which monitors primarily point mutations. It is suggested that the demonstrated isomer-specific selectivity for mutation targets within the supF gene may be indicative of a similar selectivity for one gene versus another and that such selectivity may be one determinant of relative tumorigenicity.

Base Sequence↗

PubMed1992

Analysis of the roles of CD4+ and CD8+ T cells in autoimmune diabetes of NOD mice using transfer to NOD athymic nude mice.

The NOD mouse, which spontaneously develops insulitis and overt diabetes, is a model of autoimmune type I diabetes mellitus. For the precise analysis of the roles of CD4+ and CD8+ T cells in the pathogenesis of this mouse, these subsets must be transferred into recipients that are completely free of T cells and pathological changes. We used athymic NOD nude mice, which congenitally lack mature T cells and are free of insulitis and hyperglycemia up to the age of 60 weeks, as recipients for this purpose. To the nude recipients we transferred either one of a highly purified CD4+ or CD8+ T cell subset derived from non-diabetic female NOD mice; any in vivo increase in the contaminating T cell subsets was prevented by injecting the antibody homologous to it. Most of the T cell-reconstituted recipients were treated with cyclophosphamide to promote the onset of overt diabetes. Transfer of the CD8+ T cell subset alone did not induce insulitis or hyperglycemia. In contrast, transfer of the CD4+ T cell subset alone produced insulitis, but not hyperglycemia, in all the recipients. However, the subsequent transfer of CD8+ T cells into CD4+ T cell-reconstituted recipients induced severe insulitis and hyperglycemia in almost all the recipients. In these diabetic recipients, we observed severe damage of the pancreatic islets and the infiltration of a large number of CD8+ T cells into the remaining islets; insulin-secreting beta cells were no longer detected. These results suggest that CD4+ T cells play a predominant role in the development of insulitis and that CD8+ T cells migrate into the islets and are subsequently, with the aid of CD4+ T cells, differentiated into killer cells which act against beta cells.

Animals↗

PubMed1992

Acidic fibroblast growth factor prevents death of hippocampal CA1 pyramidal cells following ischemia.

Ischemic insult induces neuronal death in the CA1 subfields of the hippocampus which are designated generally as the most vulnerable brain region. Recent studies have shown that acidic and basic fibroblast growth factors are potent trophic factors that support the survival of neurons in many brain regions including the hippocampus. Here we demonstrate that continuous infusion of acidic fibroblast growth factor into the lateral cerebral ventricles beginning 2 days before ischemia prevents the death of the CA1 pyramidal cells in the hippocampus of gerbils. Furthermore, delayed continuous administration of acidic fibroblast growth factor starting 5 min after ischemia is equally protective. The results suggest a possible physiological function for acidic fibroblast growth factor in the normal support of hippocampal CA1 pyramidal cells and neurons in some other brain regions in considering the broad spectrum of responsive neurons.

Animals↗

PubMed1992

High selectivity of polyclonal antibodies against DNA modified by diastereomeric benzo[c]phenanthrene-3,4-diol-1,2-epoxides.

Polyclonal antibodies were developed in New Zealand White rabbits against DNA modified with diastereomeric benzo[c]phenanthrene-3,4-diol-1,2-epoxide (B[c]PhDE)-1 (4-hydroxyl and epoxide cis) and B[c]PhDE-2 (4-hydroxyl and epoxide trans). Antiserum developed against B[c]PhDE-2-DNA was stereoselective. In competitive ELISA assays using wells coated with 160 fmol B[c]PhDE-2-DNA adducts, B[c]PhDE-2-DNA gave 50% inhibition at 200 fmol adducts/well. B[c]PhDE-1-DNA required a 10-fold higher amount of adducts/well to give 50% inhibition. Benzo[a]pyrene-7,8-diol-9,10-epoxide-2-DNA and 7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1-DNA caused only a 30% inhibition even at the highest doses tested (greater than 4000 fmol adducts/well). For antiserum developed against B[c]PhDE-1-DNA, 50% inhibition required 570 fmol B[c]PhDE-1-DNA adducts in wells coated with 100 fmol B[c]PhDE-1-DNA adducts. 7,12-Dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1-DNA and B[c]PhDE-2-DNA were also effective competitors: they caused 50% inhibition at 1900 and 1800 fmol adducts/well respectively. In contrast, benzo[a]pyrene-7,8-diol-9,10-epoxide-2-DNA gave no inhibition at the highest dose of competitor tested (4050 fmol adducts/well). Antisera from three rabbits immunized with B[c]PhDE-2-DNA demonstrated similar antigen specificities. The properties of these antisera differ from those reported previously for antibodies developed against benzo[a]pyrene-DNA in that they show selectivity for DNA modified by specific hydrocarbon diolepoxides, in one case for B[c]PhDE-2-DNA and in the other for B[c]PhDE-DNA or 7,12-dimethylbenz[a]anthracene-3,4-diol-1,2-epoxide-1-DNA. The specificity of these antisera will facilitate analysis of the modification of DNA by different polycyclic aromatic hydrocarbon diolepoxides.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1991

Dose-dependent differences in the profile of mutations induced by an ultimate carcinogen from benzo[a]pyrene.

Mutations in the coding region of the hypoxanthine (guanine) phosphoribosyltransferase (HPRT) gene of Chinese hamster V-79 cells were examined after exposure of the cells to a high cytotoxic dose (0.48 microM; 35% survival) and a low noncytotoxic dose (0.04 microM; 100% survival) of the ultimate carcinogen (+)-7R,8S-dihydroxy-9S,10R-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-BPDE]. Independent 8-azaguanine-resistant colonies were isolated and cDNAs were prepared by reverse transcription. The coding region of the cDNA of the HPRT gene was amplified by the polymerase chain reaction and sequenced. An examination of the DNA base sequence changes induced by different doses of (+)-BPDE demonstrated that the high dose of (+)-BPDE caused base substitution mutations almost exclusively at G.C base pairs whereas the low dose of (+)-BPDE caused mutations at both G.C and A.T base pairs. Thus, use of a low dose of (+)-BPDE allowed the detection of mutations (at A.T base pairs) that were not readily observed with a high dose of (+)-BPDE. The data also suggest that the low dose of (+)-BPDE may have caused a different profile of base substitutions at G.C base pairs and exon deletions than the high dose. The results indicate dose-dependent differences in the profile of mutations for an ultimate carcinogen.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗

PubMed1991

Polyadenylated and 3' processed mRNAs are transcribed from the mouse histone H2A.X gene.

We have isolated a cDNA clone encoding a mouse histone H2A.X from a cDNA library of teratocarcinoma F9 cells. The predicted amino acid sequence of this clone is 97% identical to human histone H2A.X. The first 119 residues of the mouse H2A.X were very similar (96-97%) to those of the major H2A histones (H2A.1 and H2A.2) of mouse and the long carboxy terminal sequence of H2A.X was homologous with those of several lower eukaryotes. Northern blot analysis revealed that this cDNA hybridized with two mRNAs in different sizes, 0.5 kb and 1.4 kb. The two mRNAs were present in tissue culture cells, and in spleen, thymus and testes of mice, but the ratio of abundance of the two transcripts differed in different cells and tissues. The shorter mRNA contained the highly conserved palindromic sequence typical of the 3' end of replication-dependent histone genes. The amount of this transcript was coupled to DNA synthesis and rapidly decreased in culture cells. It was synthesized just after the beginning of S-phase and degraded just after the end of S-phase. On the other hand, the longer mRNA was polyadenylated at 0.9 kb downstream from the palindromic sequence. This transcript was very stable when compared with the shorter one. These results indicate that these two mRNAs are transcribed from a single gene and maintained differently during the cell cycle, perhaps to maintain a partially replication-dependent level of histone H2A.X.

Amino Acid Sequence↗

PubMed1991

Novel stereoselectivity of rat liver cytochrome(s) P450 toward enantiomers of the trans-1,2-dihydrodiol of triphenylene.

Metabolism of 3H-labeled (+)-(S,S)- and (-)-(R,R)-1,2-dihydrodiols of triphenylene by rat liver microsomes and 11 purified isozymes of cytochrome P450 in a reconstituted monooxygenase system has been examined. Although both enantiomers were metabolized at comparable rates, the distribution of metabolites between phenolic dihydrodiols and bay-region, 1,2-diol 3,4-epoxide diastereomers varied substantially with the different systems. Treatment of rats with phenobarbital (PB) or 3-methylcholanthrene (MC) caused a slight reduction or less than a twofold increase, respectively, in the rate of total metabolism (per nanomole of cytochrome P450) of the enantiomeric dihydrodiols compared to microsomes from control rats. Among the 11 isozymes of cytochrome P450 tested, only cytochromes P450c (P450IA1) and P450d (P450IA2) had significant catalytic activity. With either enantiomer of triphenylene 1,2-dihydrodiol, both purified cytochrome P450c (P450IA1) and liver microsomes from MC-treated rats formed diol epoxides and phenolic dihydrodiols in approximately equal amounts. Purifed cytochrome P450d (P450IA2), however, formed bay-region diol epoxides and phenolic dihydrodiols in an 80:20 ratio. Interestingly, liver microsomes from control or PB-treated rats produced only diol epoxides and little or no phenolic dihydrodiols. The diol epoxide diastereomers differ in that the epoxide oxygen is either cis (diol epoxide-1) or trans (diol epoxide-2) to the benzylic 1-hydroxyl group. With either purified cytochromes P450 (isozymes c or d) or liver microsomes from MC-treated rats, diol epoxide-2 is favored over diol epoxide-1 by at least 4:1 when the (-)-enantiomer is the substrate, while diol epoxide-1 is favored by at least 5:1 when the (+)- enantiomer is the substrate. In contrast, with liver microsomes from control or PB-treated rats, formation of diol epoxide-1 relative to diol epoxide-2 was favored by at least 2:1 regardless of the substrate enantiomer metabolized. This is the first instance where the ratio of diol epoxide-1/diol epoxide-2 metabolites is independent of the dihydrodiol enantiomer metabolized. Experiments with antibodies indicate that a large percentage of the metabolism by microsomes from control and PB-treated rats is catalyzed by cytochrome P450p (P450IIIA1), resulting in the altered stereoselectivity of these microsomes compared to that of the liver microsomes from MC-treated rats.

Animals↗

PubMed1991

Possible mechanism of the preventive effect of BCG against diabetes mellitus in NOD mouse. I. Generation of suppressor macrophages in spleen cells of BCG-vaccinated mice.

With the aim of clarifying the mechanism of the suppressive action of BCG against insulitis and overt diabetes in NOD mice, we studied the effects of BCG on spleen cell populations and on the in vitro immune responses of spleen cells. The spleen cells of BCG-vaccinated mice showed much lower responsiveness to various mitogens such as Con A, PHA, PWM, and LPS than those of saline-treated mice. Low responsiveness to alloantigens was also observed. Flow cytometric analysis of the spleen cells revealed that Mac-1+ and Mac-2+ cells had increased while T and B cells had decreased in the BCG-vaccinated mice compared with the saline-treated mice at the time when the maximum level of inhibition of mitogen responses of BCG-vaccinated mice was observed. This suggests that the decreased in vitro immune response was due to the increase in macrophages which suppress lymphocyte functions. Support for this interpretation comes from the following two findings: (1) the restoration of mitogen responses of spleen cells when macrophages were eliminated by plastic adhesion or FACS sorting and (2) resuppression of PHA and Con A responses of plastic-nonadherent spleen cells by addition of adherent cells or flow cytometrically sorted Mac-1+ cells obtained from BCG-vaccinated mice. These results indicate the generation of suppressor macrophages after BCG vaccination and suggest that these macrophages prevent the autoimmune pathogenesis leading to diabetes in NOD mice.

Animals↗

PubMed1991

Possible mechanism of the preventive effect of BCG against diabetes mellitus in NOD mouse. II. Suppression of pathogenesis by macrophage transfer from BCG-vaccinated mice.

Our previous reports showed that a single injection of live BCG, one of the biological response modifiers, prevents insulitis and overt diabetes in NOD mice and that the suppression could be due to the generation of some type of suppressor cells in the BCG-treated mice. Furthermore, a more recent study has revealed that macrophages suppressive against a variety of lymphocyte functions can be induced by BCG, which suggests that these macrophages are involved in the suppression of the pathogenesis. To obtain valid evidence for this speculation, the effects of transfer of macrophage and T-cell fractions on the pathogenesis were examined in the present study. Transfer of macrophage-enriched spleen cell fraction harvested from the BCG-treated females to young females abolished the occurrence of spontaneous diabetes up to the age of 25 to 30 weeks. Also, macrophage transfer prevented the progress of insulitis. In contrast, transfer of a T-cell-enriched fraction did not suppress insulitis and overt diabetes. From these results, it could be concluded that the suppression of the autoimmune pathogenesis of diabetes by BCG is due to the generation of suppressor macrophages.

Animals↗

PubMed1991

Perinatal changes in bombesin-stimulated muscle contraction in rabbit stomach and colon.

Bombesin and its mammalian homologue, gastrin-releasing peptide, stimulate smooth muscle contraction and may promote the growth of gastrointestinal tissues. Isometric contraction of strips from circular muscle of the gastric fundus and longitudinal muscle of the distal colon were used to compare changes in the response to bombesin in newborn and weanling rabbits. There was an age-related qualitative change in gastric muscle from biphasic contractions including phasic and tonic components in the newborn to phasic contractions alone in the weanling. The colon contractions were tonic at both ages. In both tissues there was an age-related fivefold increase in stress in response to maximally effective concentrations of bethanechol (P less than 0.05). In contrast, in the stomach age-related decreases in the response to maximally effective concentrations of bombesin were observed, from 2930 +/- 179 mN/cm2 (98% of the maximal response to bethanechol) in the newborn to 565 +/- 81 mN/cm2 (4% of the maximal response to bethanechol) in the weanling (P less than 0.005). In the colon, a twofold increase in response to bombesin was observed, from 446 +/- 59 mN/cm2 (82% of the response to bethanechol) in the newborn to 862 +/- 11 mN/cm2 (29% of the response to bethanechol) in the weanling (P less than 0.05). No age-related changes were observed in the potency of bombesin in either tissue. Neither atropine nor tetrodotoxin altered the contractions in either tissue, suggesting that bombesin interacted directly with myocytes. There was three times as much bombesinlike immunoreactivity in the stomach compared with the colon, but no age-related changes in either tissue. In summary, by the age of weanling the stomach lost the tonic component of contraction and 80% of the efficacy of bombesin-stimulated phasic contraction that had been present in the newborn. The loss of efficacy, absolute in the stomach and relative to bethanechol in the colon, suggest that bombesin may be most important in stimulating motility in the neonatal period.

Animals↗

PubMed1991

Developmental changes in agonist-mediated colonic smooth muscle contraction in the rabbit.

We studied smooth muscle strips from rabbit distal colon to determine age-related changes in length-tension properties and agonist-mediated contraction. Strips from newborn (1-d-old) and weanling (11-wk-old) rabbits were oriented to measure isometric tension in longitudinal muscle. Active tension comprised 47 +/- 4 and 75 +/- 5% of the total tension in the newborn and weanling, respectively. Total and active tensions in the weanling were greater than in the newborn (p less than 0.001). Although the potencies for bethanechol were similar, the maximal response was nearly 9-fold greater in weanlings (6900 +/- 292 mN/cm2) versus newborns (753 +/- 112 mN/cm2), p less than 0.001. Maximal stress increased with age for bethanechol, high extracellular potassium, substance P, neurokinin A, cholecystokinin octapeptide, bombesin, and serotonin. ED50 for bethanechol, substance P, neurokinin A, and bombesin did not change with age. Serotonin was 12 times more potent in newborns versus weanlings (p less than 0.05). In contrast, cholecystokinin octapeptide was five times less potent in newborns (18.6 nM versus 3.4 nM, respectively, p less than 0.05). Substance P-induced contractions were inhibited partially by atropine. We conclude that length-tension properties of longitudinal colonic smooth muscle differ, and responses to agonists increase with age.

Animals↗

PubMed1991

Intranasal administration of His-D-Trp-Ala-Trp-D-Phe-LysNH2 (growth hormone releasing peptide) increased plasma growth hormone and insulin-like growth factor-I levels in normal men.

The effects of intranasal and iv administration of His-D-Trp-Ala-Trp-D-Phe-LysNH2 (GHRP) on plasma GH, PRL, LH, FSH, TSH, cortisol, insulin, IGF-I as well as GHRH-like immunoreactivity (LI) levels were examined in 6 healthy male subjects. An iv bolus injection of GHRP(1 micrograms/kg BW) caused a remarkable increase in plasma GH levels with a mean (+/- SE) peak of 54.9 +/- 4.2-micrograms/L. In addition an intranasal administration of GHRP resulted in a significant, dose-related increase in plasma GH with peaks of 39.6 +/- 15.3 micrograms/L at a dose of 30 micrograms/kg BW, 14.1 +/- 5.0 micrograms/L at 15 micrograms/kg BW and 7.5 +/- 5.7 micrograms/L at 5 microgram/kg BW. Plasma PRL and cortisol levels were slightly but significantly increased after iv administration of GHRP, whereas GHRP totally failed to affect plasma TSH, LH, FSH, insulin, blood sugar and GHRH-LI levels. Seven consecutive, intranasal administrations of 15 micrograms/kg BW GHRP every 8h were well tolerated in all subjects examined. During this treatment, GH responsiveness to GHRP was not attenuated by desensitization and plasma IGF-I was increased from 94.5 +/- 5.8 micrograms/L before GHRP to 125.8 +/- 6.0 micrograms/L after repeated GHRP administration. These findings indicate that intranasal administration of GHRP stimulates GH secretion and consequently enhances IGF-I production in normal subjects. If GHRP is demonstrated to be beneficial in the treatment of some patients with GH deficiency, the intranasal route of administration may be more useful than the painful injection because a prolonged period is required for the treatment.

Administration, Intranasal↗

PubMed1991

Otoplasty in microtia.

Microtia patients encountered over 9 years from 1978 to 1986 were listed. The total number of patients for the period was 155, 113 males and 42 females. The microtia occurred on the right side in 93 cases, on the left in 50 cases and bilaterally in 12 cases. Surgery was performed in 115 cases during the period. We applied a modification of the Brent method and have to date obtained good results. This method has several advantages: 1) Use of 7th and 8th rib cartilage means a relatively small amount of material, minimal surgical invasion and short operation time; 2) A more naturalistic auricle with clear grooves and ridges; 3) Preschool start completion of auricle reconstruction is possible, which contributes to the peace of mind of patient and parents.

Cartilage↗

PubMed1991

[The significance of bacillus Calmette-Guerin in the therapy of carcinoma in situ of the bladder].

We treated ten patients with carcinoma in situ of the bladder (primary type, 6 and secondary type, 4) by intravesical bacillus Calmette-Guerin therapy. All patients received 8 weekly instillation, and among them 3 patients were followed by additional instillation monthly for 7 months. Complete regression (negative biopsies and cytology study) was observed after 8 weekly instillation in all patients. To elucidate the mechanism of action of BCG on carcinoma in situ, the biopsied specimens after BCG instillation were examined light and electronmicroscopically. It was speculated that BCG might act on cancer cells in two ways: one was sloughing and denudation of the cancer cells by acute tuberculous cystitis, and the other was a role of the macrophages through immune reaction. In our study, the toxicity and complications seemed to be much severer than previously reported. Vesicoureteral reflux was observed in 6 patients. Decreased bladder capacity noted in all patients, among them radical cystectomy and colocystoplasty were performed in 2 patients under the diagnosis of bladder contracture. Although complete regression was observed in all patients after 8 weekly BCG instillation, the duration being free from cancer cells was variable. And we also discussed on the additional therapy in such patients in the literature.

Administration, Intravesical↗

PubMed1991

Acute poisoning from hair dye.

A series of 18 cases of acute hair dye (paraphenylenediamine) poisoning were reported. The characteristic features of swollen face and the chocolate brown colour of the urine were diagnostic. Asphyxia was found to be the major early challenge of life. Tracheostomy and intensive medical treatment with hydrocortisone and chlorpheniramine maleate (antihistaminic drug) and penicillin cover were life saving in all serious cases. The mild cases were successfully treated with hydrocortisone and chlorpheniramine maleate and penicillin without tracheostomy. The dye was detected in the urine by thin layer chromatography on silica gel and proved to be paraphenylenediamine. Early prompt diagnosis and clinical management proved to be life saving in both serious or mild hair dye poisoning.

Adolescent↗

PubMed1991

Sinusitis in Sudanese patients: a clinical review.

A retrospective study was carried out to show the pattern of sinusitis in Sudanese patients. Patients with sinusitis were 32% of all patients with nasal diseases. Sinusitis affected males more than females. The highest incidence of the disease was at ages 21-30 years. The maxillary sinuses were the most affected by sinusitis followed by the ethmoid and frontal sinuses respectively. The disease was rare in the sphenoid sinuses. Bacteriological review showed that Staphylococci, Streptococci and E. coli were the commonest causative organisms isolated in culture. Medical treatment by the appropriate antibiotics, antihistamines and local decongestants cured the majority of patients.

Adolescent↗

PubMed1991

An unusual foreign body in the oesophagus.

UNLABELLED: Unusual swallowed foreign bodies are uncommon in normal individuals. They may be encountered in the mentally deranged or the subnormal. A case of an unusual foreign body, two safety pins hooked together, in the upper oesophagus of a 27-year-old lady who looked apparently normal at the time of admission to hospital is reported. CASE REPORT: A 27-year-old lady presented with history of discomfort in the throat and difficulty in swallowing for two weeks. She denied having swallowed anything unusual. At the time of admission, she looked mentally normal, with normal behaviour. She had no signs of dehydration. There was tenderness on movement of the trachea. Indirect pharyngoscopy showed minimal pooling in the piriform fossae. Plan X-ray of the neck showed a foreign body in the upper oesophagus: two safety pins hooked together (Fig I and II). Under general anaesthesia, oesophagoscopy was carried and the foreign body was successfully removed. During oesophagoscopy, it was attempted to bring the two limbs of each safety pin together and to get the sharp end of the lower safety pin into the oesophagoscope. Fortunately, the lower safety pin broke at the joint. The upper safety pin was delivered in toto and the lower one in two pieces. The foreign body was tarnished suggesting that it stayed in the oesophagus for two weeks. Figure III shows the foreign body repositioned after removal. Post-operative recovery was uneventful and the patient was discharged home after five days in good condition. We met the patient accidentally after six months. She looked well and mentally stable.

Adult↗

PubMed1990

Involvement of specific placental antigen X-P2 in rat olfaction: an immunohistochemical study in the olfactory bulb.

Human placental antigen X-P2 (hPAX-P2), an antigen complex associated with cytochrome P-450 of aromatase within estrogen synthesizing tissues, has been reported to be present in a distinct group of rat primary olfactory receptors involved in suckling behavior. In this study, most of the mitral and tufted cells in the rat olfactory bulb were found to possess hPAX-P2 immunoreactivity. This suggests that the activity of these cells can be hormonally modulated and that hPAX-P2 is involved in rat olfaction not only at the receptor level but also at integrative brain levels via the secondary projecting neurons of the olfactory pathway.

Animals↗