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Biomedical subjects

M Hirose

Publications and source records attributed to M Hirose.

At least 469 records · Page 26Linked to original sources
PubMed1991

Synergistic effect of recombinant interferon-gamma and interleukin-3 on the growth of immature human hematopoietic progenitors.

Purified peripheral blood hematopoietic progenitors from children in early remission from cancer respond to recombinant human interleukin-3 (IL-3), but not to granulocyte colony-stimulating factor (G-CSF). With these purified cells as a target, we studied the effect of recombinant human interferon-gamma (IFN-gamma) on progenitor growth, using both liquid-suspension limiting dilution assay (LDA) and regular methylcellulose culture of progenitors. We found that in LDA with IL-3, IFN-gamma directly stimulated the growth of blood progenitors in a dose-dependent manner with single-hit kinetics, whereas IFN-gamma suppressed the growth of G-CSF-supported progenitors obtained from bone marrow. The stimulatory effect was also observed in methylcellulose culture, but the addition of antibodies for G-CSF, granulocyte-macrophage CSF, IL-1 alpha, IL-1 beta, IL-6, or tumor necrosis factor did not result in a decrease of the colony number, supporting further the possible direct effect of IFN-gamma on progenitor growth. These results suggest that the inhibitory effect of IFN-gamma on hematopoietic progenitors is limited to those in an advanced stage of maturation. IFN-gamma may be one of the essential lymphokines upregulating the growth of human hematopoietic progenitor cells.

Blood Component Removal↗
PubMed1991

Effects of phenolic antioxidants in low dose combination on forestomach carcinogenesis in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine.

The combined effects of low doses of promoters or carcinogens on two-stage forestomach carcinogenesis were examined in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine. Groups of 15 rats were given a single 150 mg/kg body weight intragastric dose of N-methyl-N'-nitro-N-nitrosoguanidine. Starting 1 week later they were fed a diet containing low doses of known forestomach promoters/carcinogens (0.5% caffeic acid, 0.2% catechol, 0.5% butylated hydroxyanisole, or 0.25% 2-tert-butyl-4-methylphenol), alone or in combination, or basal diet without antioxidant supplement for 35 weeks. Histopathological examination revealed the incidences of forestomach squamous cell carcinomas in animals treated with N-methyl-N'-nitro-N-nitrosoguanidine followed by caffeic acid, catechol, butylated hydroxyanisole, 2-tert-butyl-4-methylphenol, and basal diet to be 27, 20, 13, 13, and 7%, respectively, whereas the incidence increased to 80% by the combined treatment with these four chemicals. The present results thus show that although the low doses of individual promoters/carcinogens did not have significant promoting activity, their combination exerted a strong enhancing influence on rat forestomach carcinogenesis. The findings indicate the importance of summation and synergism at a low dose for agents present in the human environment.

Animals↗
PubMed1991

Partially folded state of the disulfide-reduced N-terminal half-molecule of ovotransferrin as a renaturation intermediate.

A previous report (Hirose, M., Akuta, T., and Takahashi, N. (1989) J. Biol. Chem. 264, 16867-16872) has shown that for the efficient oxidative refolding of disulfide-reduced ovotransferrin, a preincubation under reduced conditions at a low temperature is essential. To study the renaturation pathway, the disulfide-reduced N-terminal half-molecule of ovotransferrin was analyzed by CD spectrum. The reduced protein was found to take, at low temperatures, a partially folded conformation that can be distinguished from both the native and denatured states. The folded protein was in a metastable state with delta GD value of 2.2-2.8 kcal/mol at 6 degrees C. The conformation was variable depending on temperature conditions; its stability was decreased at a lower temperature (1.0-1.2 kcal/mol at 0 degrees C). Subsequent reoxidation at 6 degrees C by oxidized glutathione led efficiently the reduced protein to the correctly renatured form having the iron-binding capacity, indicating that the partially folded state is the immediate precursor to subsequent oxidative refolding.

Animals↗
PubMed1991

Impaired production of burst promoting activity by blood mononuclear cells from chronic uremic patients.

The ability of blood mononuclear cells (MNC) to produce burst promoting activity (BPA) was evaluated in 31 patients with chronic renal failure. The BPA of cells from uremic patients, with or without hemodialysis, was consistently lower than that of 17 normal donors (mean 64%, P less than 0.01). Coculture of MNC with recombinant erythropoietin (rEpo) in vitro did not increase BPA production. Five of 31 patients received in vivo treatment with rEpo (1,500 units x3/week) and showed therapeutic benefit, but in all patients the BPA production remained low. On the other hand, in four patients who were on a hemodialysis protocol and subsequently underwent renal transplantation, impaired BPA production was resolved quickly, and at the same time the number of circulating BFU-E and the hemoglobin level increased toward normal ranges. Furthermore, such impaired BPA production was not observed in patients receiving continuous ambulatory peritoneal dialysis. These observations suggest that decreased production of BPA may play a role in the development of anemia associated with chronic uremic patients, and the correction of BPA production by the improvement of hemodialysis procedure may result in more effective therapy with rEpo for those patients.

Adult↗
PubMed1991

Early infectious complications after peripheral blood stem cell autografts in children.

Seventeen children underwent marrow-ablative high-dose chemotherapy with peripheral blood stem cell autografts and were studied retrospectively to determine the type, frequency, and outcomes associated with infectious complications 3 months postgraft. The patients were kept in isolated rooms with a laminar air flow facility, but no decontamination procedures, such as gut sterilization with nonabsorbable antibiotics, nonmicrobial diet, and skin cleansing, were used. They were under their mothers' daily care to maintain good psychological conditions. After the completion of marrow-ablative chemotherapy and the infusion of stem cells, the absolute granulocyte count exceeded 0.5 x 10(9)/liter with a mean of 17.9 days (range 6-65 days). Fifteen patients developed a total of 16 febrile episodes during the first 4 week period, and the confirmed diagnoses were mucositis (12), enterocolitis (nine), septicemia (four), central venous catheter-associated infection (three), pneumonia (one), perianal abscess (one), and possible invasive fungal infection (one). All episodes were successfully treated with parenteral antibiotic therapy, and no patient died of infectious complications. The observations suggest that high-dose chemotherapy can be performed safely with simple and efficient patient management protocol followed by peripheral blood stem cell autografts.

Adolescent↗
PubMed1991

Somatosensory evoked potentials to median nerve stimulation after partial section of the corpus callosum.

Cortical somatosensory evoked potentials (SEPs) to electrical stimulation of the median nerve were studied in four patients with intractable epilepsy who had undergone callosotomy and in a patient with infarction in the corpus callosum in order to determine whether the corpus callosum was involved in the generation of ipsilateral frontal components. Both pre- and postoperative SEPs were recorded in three of four epileptic patients. There were no significant differences in the latencies and amplitudes of the bilateral frontal components (P20, N26) between pre- and postoperative recordings. Furthermore, irrespective of the extent of the section or lesion in the corpus callosum, the nature of the impairment and the existence of the disconnection syndrome, the SEP findings showed no significant differences compared with those of normal subjects. It thus appears unlikely that the ipsilateral SEP responses are transmitted from the contralateral hemisphere through at least the anterior portion of the corpus callosum.

Adult↗
PubMed1991

Effects of deoxyadenosine on ribonucleotide reductase in adenosine deaminase-deficient lymphocytes.

To explore the relationship between ribonucleotide reductase and immunodysfunction in adenosine deaminase deficiency, the effects of deoxyadenosine on ribonucleotide reductase in ADA-deficient lymphocytes was investigated. An assay system for ribonucleotide reductase in intact permeabilized lymphocytes was developed to approximate physiological conditions. The activity of cytidine diphosphate (CDP) reductase in resting but not in proliferating lymphocytes in culture was inhibited by 1 to 10 mumol/L deoxyadenosine. The resting cells were protected from the toxicity of 1 mumol/L deoxyadenosine by 5 mmol/L nicotinamide or 30 mumol/L deoxycytidine and from that of 10 mumol/L deoxyadenosine by 30 mumol/L deoxycytidine. These findings suggest that depletion of nicotinamide adenine dinucleotide might be the principal cause of death in resting lymphocytes with ADA deficiency. It is concluded that the mechanism of deoxyadenosine toxicity on non-replicating lymphocytes, which may not be mediated by ribonucleotide reductase inhibition, is closely related to the mechanism of immunodysfunction in patients with ADA deficiency.

Adenosine Deaminase↗
PubMed1991

Comparative study on the cardio-respiratory change during prostaglandin E1-induced hypotension in the patients in the supine and prone position.

Prostaglandin E(1)-induced hypotension (25% reduction from the preadministration level in mean arterial pressure) was applied to thirteen patients. Eight patients among them were operated in the supine position (group I) and other five in the prone position (group II). The maintenance dose of PGE(1) was considerably lower in group II than in group I (0.067 micro g.kg(-1).min(-1) vs. 0.119 micro g.kg(-1).min(-1)). In group I, there was a significant increase in CI, with a significant decrease in SVRI and PVRI during PGE(1)-induced hypotension. Such a high dose of PGE(1) (0.119 micro g.kg(-1).min(-1)) was considered to have a direct dilating action on the systemic resistance bed as well as on the pulmonary vasculature. It was considered that the suppression of hypoxic pulmonary vasoconstriction could be a mechanism to increase venous admixture during PGE(1)-induced hypotension. In group II, there was no significant increase in CI, and no significant decrease in SVRI and PVRI. PGE(1)-induced hypotension can be safely applied to the anesthetized patients, but we should be careful to apply it to the patients in the prone position, because lower dose of PGE(1) can induce severe hypotension, which is not accompanied by the increase in CI as occurres in the patients in the supine position.

Journal Article↗
PubMed1991

Mutagenic properties of 2-amino-N6-hydroxyadenine in Salmonella and in Chinese hamster lung cells in culture.

The mutagenicity of the base analogue, 2-amino-N6-hydroxyadenine (AHA), was tested in Salmonella typhimurium TA100 and TA98 and in Chinese hamster lung (CHL) cells. AHA showed very potent mutagenicity in TA100 without S9 mix, inducing 25,000 revertants/micrograms. The mutagenicity increased about 2-fold upon addition of S9 mix containing 10 microliters S9. AHA was found to be one of the strongest mutagens for TA100. Addition of S9 mix containing 100 microliters S9 induced no significant increase of revertants with AHA at amounts up to 50 ng per plate. AHA was also mutagenic for the frameshift mutant, TA98, without S9 mix, the mutagenicity for TA98 being about 1/1000 of that for TA100. When the mutagenicity of AHA was tested in CHL cells, with diphtheria toxin resistance (DTr) as a selective marker in the absence of S9 mix with a 3-h treatment of cells, DTr mutants increased dose-dependently at concentrations of 2.5-15 micrograms/ml. When cells were incubated with AHA for 24 h, a 200-fold increase in the number of DTr mutants was observed; the mutagenicity was 500-fold higher than that of ethyl methanesulfonate. This marked increase of mutagenicity by prolonged incubation may indicate that AHA induces mutations mainly after incorporation into DNA. The addition of a small amount of S9 increased the mutagenicity obtained with a 3-h treatment 2-fold, but a larger amount of S9 decreased the mutagenicity as was found with S. typhimurium TA100.

Adenine↗
PubMed1991

The formation of heart DNA adducts in F344 rat following dietary administration of heterocyclic amines.

Most heterocyclic amines formed during the cooking of meat and fish have been shown to form adducts in the livers of rats. Recently, however, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), administered in the diet to Fischer 344 (F344) rats for 4 weeks, was shown to produce the highest levels of adducts in the heart. In the present study 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-amino-6-methyldipyrido[1,2-a:1',2'-d]imidazole (Glu-P-1) were given to F344 rats at carcinogenic dose levels (IQ 0.03%, MeIQx 0.04%, Trp-P-1 0.015%, Glu-P-1 0.05%) in the diet for 4 weeks. DNA adducts in the liver and heart were analyzed by 32P-postlabeling. DNA adducts were demonstrated to appear in the hearts of all animals exposed to heterocyclic amines at the following levels: IQ, 1.8 adducts/10(7) nucleotides, MeIQx, 3.8/10(7) ntd, Trp-P-1, 20/10(7) ntd and Glu-P-1, 7.2/10(7) ntd. Values for the heart were 10-20% of the respective liver adduct levels. Heart adducts increased linearly throughout the observed period when MeIQx was administered for up to 40 weeks. When MeIQx feeding was discontinued after 20 weeks and the animals subsequently given the basal diet, the adduct level at 20 weeks did not change during the following 20 weeks. A possible role for heart DNA alterations caused by food-borne heterocyclic amines in the development of age-related myopathies and cardiovascular disease is not inconceivable.

Administration, Oral↗
PubMed1991

Effects of butylated hydroxyanisole pretreatment on low dose N-methyl-N'-nitro-N-nitrosoguanidine- or N,N-dibutylnitrosamine-induced rat forestomach or esophageal carcinogenesis.

The effects of butylated hydroxyanisole (BHA) pretreatment on subsequent low dose N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or N,N-dibutylnitrosamine (DBN) treatment on forestomach or esophageal carcinogenesis were investigated in male F344 rats. Groups of animals were pretreated with 2% BHA or basal diet alone for 24 weeks and then were given 20 mg/kg body wt MNNG once every 2 weeks, 0.025% DBN in drinking water continuously or basal diet alone for the subsequent 24 weeks. Further groups of rats were similarly treated with BHA or basal diet alone for 24 weeks, placed on basal diet for the next 24 weeks and then treated with MNNG, DBN or basal diet alone for the subsequent 24 weeks. Animals were killed 48 or 72 weeks after the beginning of the experiment. Histopathological examination showed that the incidence of forestomach tumors was not significantly affected by the BHA pretreatment in the MNNG-treated groups. On the other hand, the incidence of esophageal squamous cell carcinomas was lower in the group pretreated with BHA followed by DBN than in that treated with basal diet followed by DBN (48 week experiment). There was no significant difference in esophageal tumor incidence in the 72 week experiment. The results thus indicate that continuous treatment with 2% BHA for 24 weeks does not exert initiating activity on forestomach and esophageal epithelia.

Animals↗
PubMed1991

Modifying effects of the naturally occurring antioxidants gamma-oryzanol, phytic acid, tannic acid and n-tritriacontane-16, 18-dione in a rat wide-spectrum organ carcinogenesis model.

The modifying effects of the naturally occurring antioxidants gamma-oryzanol, phytic acid, tannic acid and n-tritriacontane-16, 18-dione (TTAD) were investigated in a rat wide-spectrum organ carcinogenesis model. Animals were initiated with two i.p. injections of 1000 mg/kg body wt 2,2'-dihydroxy-di-n-propylnitrosamine (DHPN) followed by two i.g. administrations of 1500 mg/kg body wt N-ethyl-N-hydroxy-ethylnitrosamine (EHEN), and then three s.c. injections of 75 mg/kg body wt 3,2'-dimethyl-4-aminobiphenyl (DMAB) during the first 3 weeks. Starting 1 week after the last injection, groups of rats received diet containing 1% gamma-oryzanol, 2% phytic acid, 0.2% TTAD or 1% tannic acid or basal diet alone for 32 weeks. Animals were then killed and complete autopsy was performed at the end of week 36. Histological examination revealed enhancement of lung carcinogenesis by gamma-oryzanol, and the incidence of urinary bladder papillomas to be increased by phytic acid. On the other hand, TTAD inhibited hepatic and pancreatic carcinogenesis. Phytic acid and tannic acid were marginally effective in inhibiting hepatic and colon carcinogenesis respectively. The results thus indicated that naturally occurring antioxidants each exert specific modifying effects depending on the organ site and indicate that wide-spectrum carcinogenesis models are useful for defining complex influences.

Adenoma↗
PubMed1991

Presence of carcinogenic heterocyclic amines in urine of healthy volunteers eating normal diet, but not of inpatients receiving parenteral alimentation.

For estimation of human exposures to carcinogenic heterocyclic amines, the amounts of four compounds, 3-amino-1, 4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), in human urine were measured. Twenty-four hour urine specimens were collected from ten healthy volunteers eating normal diet (five males and five females) and three inpatients (two males and a female) receiving parenteral alimentation, and the levels of the four heterocyclic amines were measured by HPLC after partial purification by treatment with blue cotton and ion exchange column chromatography. Trp-P-1, Trp-P-2, PhIP and MeIQx were detected in the 24 h urine samples of all healthy volunteers at levels of 0.04-1.43 ng, 0.03-0.68 ng, 0.12-1.97 ng and 11-47 ng respectively. As 1.8-4.9% of an oral dose of MeIQx is reported to be excreted unchanged in the urine, the daily exposure of humans to MeIQx was estimated to be 0.2-2.6 micrograms/person. The four heterocyclic amines were not detected in the urine of parenterally fed inpatients. These results indicate that humans are continually exposed to carcinogenic heterocyclic amines in food, and these compounds may not be formed endogenously.

Adolescent↗
PubMed1991

Role of an intrachain disulfide bond in the conformation and stability of ovalbumin.

Ovalbumin, which contains one intrachain disulfide bond and four cysteine sulfhydryls, was reduced with dithiothreitol under non-denaturing conditions, and its conformation and stability were compared with those of the disulfide-bonded form. The CD spectrum in the far-UV region revealed that the overall conformation of the reduced form is similar to that of the disulfide-bonded one. Likewise, the inaccessibility to trypsin and the non-reactivity of the four cysteine sulfhydryls, exhibited by the native disulfide-bonded ovalbumin, were still retained in the disulfide-reduced form. Thus, the reduced ovalbumin appeared to substantially take the native-like conformation. However, the near-UV CD spectrum slightly differed between the native and disulfide-reduced forms. Protein alkylation with a fluorescent dye and subsequent sequence analysis showed that the two sulfhydryls (Cys73 and Cys120) originating from the disulfide bond are highly reactive in the reduced form. Furthermore, upon proteolysis with subtilisin, the N-terminal side of Cys73 was cleaved in the reduced form, but not in the disulfide-bonded one. Upon heat denaturation, the transition temperature of the reduced form was lower, by 6.8 degrees C, than that of the disulfide-bonded one. Thus, we concluded that ovalbumin has a native-like conformation in its disulfide-reduced form, but that the local conformation of the reduced form fluctuates more than that of the disulfide-bonded one. Such local destabilization may be related to the decreased stability against heat denaturation.

Amino Acid Sequence↗
PubMed1991

Induction of renal cell tumors in rats and mice, and enhancement of hepatocellular tumor development in mice after long-term hydroquinone treatment.

Hydroquinone (HQ) was administered to F344 rats and B6C3F1 mice of both sexes at a level of 0.8% in the diet for two years. This treatment induced renal tubular hyperplasia as well as adenomas, predominantly in males of both species, and was associated with chronic nephropathy in rats. In addition, the occurrence of epithelial hyperplasia of the renal papilla was increased in male rats. Foci of cellular alteration of the liver were significantly reduced in number by HQ in rats, but in contrast, were increased in mice, where development of hepatocellular adenoma was also enhanced in males. The incidence of squamous cell hyperplasia of the forestomach epithelium was significantly higher in mice of both sexes given HQ than in the controls, but no corresponding increase in tumor development was observed. The present study strongly indicates potential renal carcinogenicity of HQ in male rats and hepatocarcinogenicity in male mice. Thus, it is possible that HQ, which is present in the human environment, may play a role in cancer development in man.

Animals↗
PubMed1991

Modifying effects of various chemicals on preneoplastic and neoplastic lesion development in a wide-spectrum organ carcinogenesis model using F344 rats.

Modifying potentials of various chemicals on tumor development were investigated in a wide-spectrum organ carcinogenesis model using male F344/DuCrj rats. The animals were treated with N-nitrosodiethylamine (100 mg/kg body weight, ip, single injection at the commencement of the study), N-methyl-N-nitrosourea (20 mg/kg body weight, ip, 4 times during weeks 1 and 2) and N-bis(2-hydroxypropyl)nitrosamine (0.1% in drinking water, during weeks 3 and 4) for multi-organ initiation and then were given one of 14 test chemicals including 6 hepatocarcinogens, 7 non-hepatocarcinogens and 1 non-carcinogen, or basal diet for 16 weeks. All rats were killed at the end of week 20, and the major organs were carefully examined for preneoplastic and neoplastic lesions. Immunohistochemical demonstration of glutathione S-transferase-positive foci was also used for quantitative assessment of liver preneoplastic lesion development. Modifying effects were shown for 11 out of 14 test agents in the liver, forestomach, glandular stomach, lung, urinary bladder or thyroid, 7 of them targeting more than two organs. This was the first demonstration to our knowledge that clofibrate possesses enhancing potential for urinary bladder carcinogenesis and an inhibiting effect on thyroid carcinogenesis. Caprolactam showed no effect in any organ, in agreement with its established inactivity. The results indicated that the system could be reliably applied as a medium-term multiple organ bioassay for assessment of the modification potential of test agents in unknown target sites.

Administration, Oral↗
PubMed1991

Organ-specific modification of tumor development by low-dose combinations of agents in a rat wide-spectrum carcinogenesis model.

The combined effects of low doses of various carcinogens and carcinogenesis modifiers on tumor development were investigated by using a wide-spectrum organ carcinogenesis model in F344 rats. These agents were administered as three groups: (1) a group of known hepatocarcinogens; (2) a group of nitroso compounds having various target organ specificities; and (3) a group of antioxidants having various inhibiting or enhancing activities depending on the target organ. Doses were used which were generally below the known effective level for the individual chemical. These groups of chemicals were administered with or without prior administration of N-diethylnitrosamine (100 mg/kg body wt., i.p.), N-methylnitrosourea (4 x 20 mg/kg body wt., i.p.) and dihydroxy-di-N-propylnitrosamine (0.1% in drinking water for 2 weeks). The hepatocarcinogen group in combination with various nitroso compounds increased the incidences of liver hyperplastic nodules and hepatocellular carcinomas. In contrast, incidences were clearly reduced when the hepatocarcinogens and/or the nitroso compounds were administered in combination with the antioxidants. For the urinary bladder, the combination with nitroso compounds and antioxidants enhanced cancer development, and the addition of hepatocarcinogens further increased tumorigenesis. For the glandular stomach, additive effects on the numbers of pepsinogen isozyme 1-altered pyloric glands, a putative preneoplastic lesion, were produced by the combination treatment of antioxidants and the nitroso compounds. No synergistic effects on tumor development were seen in other organs. The results of the present study demonstrated that combinations of various compounds at low doses can additively or synergistically exert either enhancing or inhibitory effects on the development of preneoplastic and neoplastic lesions in different organs in a single model having a wide spectrum of organ effects.

Animals↗