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Biomedical subjects

M Kawabe

Publications and source records attributed to M Kawabe.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of fasting subjects' posture on 13C-urea breath test for detection of Helicobacter pylori infection.

BACKGROUND: Although many factors that may affect the 13C-urea value have been verified, no literature is available regarding the effect of the posture of the patient on the shape of the delta 13C excretion curve. In an effort to contribute to the development of a simple and standard procedure for the 13C-urea breath test, we investigated whether either the posture of the patient during the procedure or the mouthwash after dosing affects the shape of the delta 13C excretion curve. MATERIALS AND METHODS: Seventy-two Helicobacter pylori-infected subjects were divided into four groups according to the position during procedure and the mouthwash after dosing: group A, in the supine position with mouthwash; group B, in the sitting position with mouthwash; group C, changed position by rolling with mouthwash; and group D, changed position (as did group C) without mouthwash. Absolute values of delta 13C at each sampling point were compared in the four groups. RESULTS: delta 13C values in group A gradually increased until the 15-minute point; those in group B were almost stable from 5 to 30 minutes, and those in group C peaked at the 5-minute point, then decreased until 30 minutes, the values becoming similar at the 20-minute point. Significant differences were seen between groups A, B, C, and D at the 5- and 10-minute points. CONCLUSION: These results suggest that posture and mouthwash affect delta 13C value at the 5- and 10-minute points. Sampling at 20 (maybe 15 or 30) minutes for fasting patients in a sitting position is considered to be appropriate for detection of H. pylori infection in a standard two-sampling-point 13C-urea breath test.

Breath Tests↗
PubMed1996

Lack of tumor promoting effects of KCB-1, a recombinant human basic fibroblast growth factor, on two-stage skin carcinogenesis in female CD-1 (ICR) mice.

Skin tumor promoting and co-promoting potentials of KCB-1, a recombinant human basic fibroblast growth factor, were investigated in a two-stage skin carcinogenesis model using female ICR mice. Animals were allocated to either normal (non-injured) or injured skin groups, and given a single topical application of dimethylbenz[alpha]anthracene (DMBA) at 100 micrograms/mouse to fur-clipped back skin. One week after the DMBA initiation step, mice were injected with KCB-1 (0.4, 4.0 and 40 micrograms/mouse, s.c.) and/or 12-O-tetradecanoylphorbol-13-acetate (TPA) at 4.0 micrograms/mouse twice a week until the termination at week 20. The treatment with KCB-1 was not associated with any increases of papillomas and hyperplasias in either the normal or the wounded skin cases. High incidences and multiplicities of skin papillomas and hyperplasias developed in TPA-treated groups. The positive control TPA promotion was not influenced by the KCB-1 treatment in the present initiation/promotion protocol. Thus, KCB-1 exerted no tumor promoting effects on mouse skin two-stage carcinogenesis, and also no amplification activity for the established skin tumor promoter TPA.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1996

Subchronic toxicity study of L-isoleucine in F344 rats.

A subchronic toxicity study with L-isoleucine was conducted using F344 rats. Groups of 10 rats of each sex were given diet containing 0, 1.25, 2.5, 5.0, or 8.0% L-isoleucine for 13 wk. No treatment-related effects were observed in terms of body weight change, food consumption or hematology. In both sexes given 8.0% L-isoleucine, increased or a tendency for increased urine volume and relative kidney weights were observed. Furthermore, the high-dose L-isoleucine treatment brought about an elevation of urinary pH and variations in serum electrolytes. However, histopathological alterations related to these changes were not observed in any organs of either sex. In conclusion, the present study demonstrated that L-isoleucine possessed minimal toxicity at dietary levels of 5.0% and 8.0%, while it did not exert any adverse affects at a dietary level of 2.5% or less.

Animals↗
PubMed1996

Chemically induced lung and forestomach neoplasias in transgenic mice carry mutant forms of the human c-Ha-ras transgene.

Susceptibility to lung carcinogens and genetic changes in neoplastic lesions were investigated in transgenic mice carrying a human hybrid c-Ha-ras gene, encoding a prototype p21 gene product. Nine-week-old male and female transgenic mice and non-transgenic littermates were injected i.p. with 6-nitrochrysene (6NC) three times biweekly or administered urethane in their drinking water for 3 weeks. Control mice were given dimethylsulfoxide (DMSO), the solvent for 6NC, alone. The incidences of lung adenocarcinomas were four out of seven female (57%) transgenic mice treated with 6NC and three out of three males (100%) and three out of three females (100%) receiving urethane. No adenocarcinomas were observed in control animals or non-transgenic mice. Adenomas developed in all treated groups, but the incidence and multiplicity were higher in transgenic animals than in their non-transgenic counterparts. In the 6NC-treated group, forestomach papillomas and squamous cell carcinomas were also observed in both male (25 and 50%) and female (56 and 33%) transgenic mice. PCR-SSCP and DNA sequence analysis of these induced lesions revealed point mutations at codon 61 of transgenic human c-Has-ras, from CAG (Gln) to CTG (Leu) or CAG (Gln) to AAG (Lyn) in lung hyperplasias (two out of three), an adenoma (one out of two), adenocarcinomas (five out of seven) and forestomach squamous cell carcinomas (four out of five). Mutations were not observed in forestomach papillomas. No changes in mouse Ha-ras or Ki-ras were found in any lesions. Furthermore, p21 overexpression was not evident in lung or forestomach tumors on immunohistochemical analysis. These findings indicate a high sensitivity to lung carcinogens in transgenic mice carrying the human c-Ha-ras gene and that this might be effected by mutational activation.

Animals↗
PubMed1995

Lack of carcinogenicity of monosodium L-glutamate in Fischer 344 rats.

Monosodium L-glutamate (MSG) was administered to groups of 50 male and 50 female Fischer 344 rats in the diet at levels of 0, 0.6, 1.25, 2.5 and 5.0% for a 2-yr period. Survival of dosed and control rats of both sexes was comparable, although animals receiving 5.0% MSG showed a trend towards (or significant) growth retardation. Urinary biochemistry values indicated increased pH and Na+ levels and decreased K+ in rats of both sexes given 2.5 or 5.0%. However, no significant increases in proliferative or neoplastic lesion development in the urinary tract were observed in any MSG-treated animals. In addition, occurrences of neoplastic lesions in other organs did not differ between treated and control groups. The present study thus did not demonstrate any long-term carcinogenic effect of MSG administered to rats at levels up to 5.0% in the diet.

Animals↗
PubMed1994

Effects of combined treatment with phenolic compounds and sodium nitrite on two-stage carcinogenesis and cell proliferation in the rat stomach.

The effects of combined treatment with NaNO2 and phenolic compounds on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) stomach carcinogenesis were investigated in F344 rats. In the first experiment, groups of 15-20 male rats were treated with an intragastric dose of 150 mg/kg body weight of MNNG, and starting 1 wk later, were given 2.0% butylated hydroxyanisole, 0.8% catechol, 2.0% 3-methoxycatechol or basal diet either alone or in combination with 0.2% NaNO2 in the drinking water until they were killed at week 52. All three antioxidants significantly enhanced forestomach carcinogenesis without any effect of additional NaNO2 treatment. However, in the absence of MNNG pretreatment, the grade of forestomach hyperplasia in the catechol and 3-methoxycatechol groups was significantly increased by the combined treatment with NaNO2. In a second experiment, the combined effects of various phenolic compounds and NaNO2 on cell proliferation in the upper digestive tract were examined. Groups of 5 rats were given one of 24 phenolic compounds or basal diet either alone or in combination with 0.3% NaNO2 for 4 weeks and then killed. Particularly strong enhancing effects in terms of thickness of the forestomach mucosa were seen with t-butylhydroquinone (TBHQ), catechol, gallic acid, 1,2,4-benzenetriol, dl-3-(3,4-dihydroxyphenyl)-alanine and hydroquinone in combination with NaNO2. In the glandular stomach, similar enhancing effects were evident in 11 cases, and in the esophagus with phenol, TBHQ and gallic acid. These results demonstrate that NaNO2 can augment cell proliferation induced in the stomach epithelium by various phenolic compounds.

Animals↗
PubMed1993

[Basic study of bone mineral density in os calcis by single energy X-ray absorptiometry].

We studied bone mineral density (BMD) in the os calcis by means of single energy X-ray absorptiometry (SXA), and BMD in the third lumbar spine by means of dual energy X-ray absorptiometry (DXA), results were as follows. (1) The doses absorbed in SXA at the exposure site and the opposite site were measured by thermoluminescent dosimetry. The dose absorbed in SXA may be lower than that in DXA. (2) The BMD of the os calcis was measured in 30 female volunteers by SXA and that of the third lumbar spine by DXA, and age, weight, height, and consequences of physical exertion were investigated. BMD as determined by SXA was significantly correlated with that determined by DXA (r = 0.65). BMD as determined by SXA and DXA tended to decrease with age, to increase with height and weight, and to be significantly higher in those who made some physical exertion. In conclusion, SXA may be a useful method for the measurement of BMD.

Absorptiometry, Photon↗
PubMed1993

Subchronic toxicity study of methyl hesperidin in mice.

A subchronic toxicity study of methyl hesperidin was performed using B6C3F1 mice. The flavonoid was administered to groups of ten males and ten females in dietary levels of 0, 0.3, 0.6, 1.25, 2.5 and 5.0% for 13 weeks. No significant treatment-related differences were found in data for body weights, food and water consumption, hematology, clinical chemistry and organ weights. Furthermore, no effects of treatment were observed on gross and histopathological examination of the major organs. The present experiment thus demonstrated that methyl hesperidin exerts no obvious toxic effects in mice of either sex when administered at a level as high as 5.0% in the diet.

Administration, Oral↗
PubMed1993

Subchronic oral toxicity study of captafol in B6C3F1 mice.

The effects of subchronic administration of captafol were studied in B6C3F1 mice given dose levels of 0, 0.3, 0.625, and 1.25% in the diet for 12 wk. There was a dose-related decrease in body weight gain during the 12-wk experiment and a loss of body weight in the 1.25% group of both sexes. Whiles the mice given captafol consumed less diet than the control mice, this was not directly dose-related. The relative weights of liver demonstrated a tendency for dose-dependent increase. Light-microscopic examination revealed cytoplasmic vacuolar degeneration, depending in severity on the dosage, in the livers of both sexes given captafol. In conclusion, the findings obtained from the present subchronic toxicity study indicated the liver to be a primary target organ.

Administration, Oral↗
PubMed1993

No enhancing effects of calcium/magnesium salts of L-glutamate and L-ascorbate on tumor development in a rat medium-term multiorgan carcinogenesis bioassay.

Calcium/magnesium salts of L-glutamate and L-ascorbate were tested for modification potential using a rat multiorgan carcinogenesis bioassay. Following sequential treatment with three different carcinogens (diethylnitrosamine, N-methylnitrosourea, and dihydroxydi-N-propylnitrosamine) over a 4-wk period, rats were given diet containing 5% monocalcium di-L-glutamate tetrahydrate (Ca-glutamate), 2.5% monomagnesium di-L-glutamate tetrahydrate (Mg-glutamate), 5% L-glutamic acid, 5% monocalcium di-L-ascorbate dihydrate (Ca-ascorbate), 2.5% monomagnesium di-L-ascorbate dihydrate (Mg-ascorbate), or 5% L-ascorbic acid for 16 wk. Body weight increase was slightly suppressed in the groups receiving Ca-ascorbate, Mg-ascorbate, and ascorbic acid supplementation after the carcinogen treatments. While administration of Ca-glutamate or Ca-ascorbate raised urinary pH, ascorbic acid values were decreased. Concentrations of calcium and magnesium ions in the urine increased after ingestion of Ca-glutamate or Ca-ascorbate, and Mg-glutamate or Mg-ascorbate, respectively, but phosphorus levels decreased in all groups given calcium and magnesium salts. No consistent treatment-related changes in the concentrations of sodium or potassium ions in the urine were detected. Histopathological investigation at wk 20 did not demonstrate any modification of tumorigenesis with regard to the incidence of frequency of lesions developing in the various target organs/tissues. The present results thus revealed no apparent enhancement of carcinogenesis at any site, including the urinary system, by calcium or magnesium salts using the present rat multiorgan carcinogenesis bioassay.

Animals↗
PubMed1993

Effects of interferon-alpha treatment on hepatitis B virus antigen-specific immunologic responses in patients with chronic hepatitis B.

Studies were undertaken to evaluate the relationship between the immune responses and the effectiveness of interferon-alpha treatment in 21 patients with HBeAg-positive chronic active hepatitis. Peripheral blood mononuclear cells (PBMC), obtained on four occasions during an 8-week course of IFN-alpha therapy, were cultured with recombinant HBcAg, purified HBeAg or pokeweed mitogen (PWM). During follow-up for 6 months after therapy, clearance of serum HBeAg was observed in eight patients designated as responders. Immunological responses of PBMC obtained before treatment did not differ between responders and non-responders. In responders, IFN-gamma and anti-HBc production was depressed during therapy, but recovered to above the pretreatment level at the end of and/or after cessation of therapy, while lymphocyte proliferation was enhanced during therapy with a subsequent decline to baseline value. In non-responders, such changes were modest throughout the study, and anti-HBc response remained decreased even after cessation of therapy. These results indicate that PBMC of responders have immunologically different responses to IFN-alpha therapy when compared with non-responders.

Adolescent↗
PubMed1993

Intermittent minibolus oral vitamin D3 in CAPD patients with resistant parathyroid hormone values.

Pulse vitamin D3 (3-5 micrograms po, twice a week) has been proposed for individuals with hyperparathyroidism resistant to daily po vitamin D3 therapy. While pulse vitamin D3 is effective, concerns regarding oversuppression of parathyroid hormone (PTH) values leading to adynamic bone disease have arisen. In view of these concerns, minibolus vitamin D3 po therapy was utilized in dosages varying from 0.25-1.0 micrograms twice a week in an effort to control elevated PTH values in patients who failed standard daily vitamin D3 therapy. Eleven patients were changed to minibolus vitamin D3 therapy from standard daily treatment (6 women, 5 men; mean age 55.8 +/- 14 years), on continuous ambulatory peritoneal dialysis (CAPD) for an average of 28.4 +/- 23 months. The mean intact PTH (iPTH) values on 0.25 microgram/day decreased by 54.5 +/- 167.8 pg/mL compared to pretreatment values. The mean iPTH on minibolus vitamin D3 therapy decreased by 165.1 +/- 104 pg/mL. The response to minibolus vitamin D3 was not truly predicted by the baseline PTH values. While the average decrease in PTH was greatest on 1.0 microgram two times a week, 2 patients experienced a decrease greater than 200 pg/mL in PTH on a lower dose. The greatest effect on PTH with minipulse vitamin D3 occurred when iPTH was < or = 500 pg/mL. While total calcium increased on daily vitamin D3, there was no significant change with minipulse therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1992

Lack of carcinogenicity of tragacanth gum in B6C3F1 mice.

Tragacanth gum was administered at dietary levels of 0 (control), 1.25 and 5.0% to groups of 50 male and 50 female B6C3F1 mice for 96 wk after which all animals were maintained on a basal diet without tragacanth gum for a further 10 wk. Mean body weights of females in the 5.0% and 1.25% groups were lower than those of the controls after 11 and 16 wk, respectively. However, there were no treatment-related clinical signs or adverse effects on survival rate, urinalysis, haematology, blood biochemistry and organ weight. While detailed histopathology revealed the development of squamous cell hyperplasias, papillomas and one carcinoma in the forestomach, there was no significant treatment-related increase in the incidence of any preneoplastic or neoplastic lesion. Thus, under the experimental conditions used, tragacanth gum was not carcinogenic in B6C3F1 mice of either sex.

Animals↗
PubMed1992

Influence of caffeic acid and other o-dihydroxybenzene derivatives on N-methyl-N'-nitro-N-nitrosoguanidine-initiated rat forestomach carcinogenesis.

Promotion effects of the o-dihydroxybenzene derivatives, protocatechuic acid (PCA), dopamine hydrochloride (DAH), dl-dopa and caffeic acid on forestomach and glandular stomach carcinogenesis were investigated in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 20 male F344 rats were given a single intragastric administration of 150 mg/kg body wt MNNG and starting 1 week later than received diet containing 1.5% PCA, 1.5% DAH, 1.5% dl-dopa or 1% caffeic acid or basal diet alone for 51 weeks and then killed. Other groups of 10-15 rats were given PCA, DAH, dl-dopa or basal diet alone without the MNNG pretreatment. On histological assessment, the incidences of forestomach papillomas and squamous cell carcinomas were significantly enhanced in the group treated with caffeic acid (95 and 100%) as compared with the control values (35 and 10%). Although the incidence was not different, the number of papillomas per rat in the group given DAH (0.79 +/- 0.79) was also significantly increased (0.35 +/- 0.49). PCA and dl-dopa treatments did not modify the development of neoplastic lesions in the forestomach epithelium to any significant extent. None of the four chemicals enhanced glandular stomach carcinogenesis. The results thus demonstrated that whereas caffeic acid and DAH respectively, exert strong and weak promotion activity for rat forestomach carcinogenesis this promotion potential is not shared by all dihydroxybenzene derivatives. An influence of substituents in the para position in addition to the o-dihydroxy moiety is indicated.

Adenocarcinoma↗
PubMed1992

Inorganic alkalizers and acidifiers under conditions of high urinary Na+ or K+ on cell proliferation and two-stage carcinogenesis in the rat bladder.

Effects of alkalizers and acidifiers on bladder cell proliferation and two-stage carcinogenesis were investigated under conditions of high urinary Na+ or K+. Animals were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then received Na3PO4, NaH2PO4, NaCl, NaH2PO4 + NaCl, K3PO4, KH2PO4, KCl, KH2PO4 + KCl or no chemical supplement in the diet from weeks 5 to 8 and from weeks 12 to 20. During weeks 9 to 11, the rats were fed 3% uracil in their diet for acceleration of promotion. Na3PO4 or K3PO4 induced marked natriuresis or kaluresis and alkalinuria associated with strong promoting potential for bladder carcinogenesis. NaH2PO4 induced moderate natriuresis and aciduria and exhibited weak promoting activity. NaH2PO4 + NaCl or KH2PO4 + KCl caused marked increase in the respective cation levels and aciduria with elevation of promotion as compared to NaH2PO4 or KH2PO4 alone. NaCl or KCl induced moderate natriuresis or kaluresis and did not alter urinary pH. NaCl but not KCl also exerted weak promoting activity for bladder carcinogenesis. Increased DNA synthesis after test chemical exposure for 8 weeks and morphological alterations observed by scanning electron microscopy in the bladder epithelium were only quantitatively linked with promoting activity in the Na3PO4 case. With the other treatments no clear correlation between early cell proliferation and promotion potential was apparent. The present results suggest that although elevation in urinary Na+ or K+ level may be an essential factor for promotion of rat bladder carcinogenesis, the action of these cations may depend strongly on urinary alkalinity.

Animals↗
PubMed1992

Effects of recombinant human granulocyte colony-stimulating factor on neutrophil functions in aged animals.

We have studied the effects of recombinant human granulocyte colony-stimulating factor (rG-CSF) on granulopoiesis and neutrophil functions in aged rats and aged mice. We subcutaneously injected rG-CSF or control vehicle into aged rats (22 months old and 25 months old) for 7 consecutive days, counted the peripheral neutrophils and evaluated the functions of neutrophils isolated from venous blood. The peripheral neutrophil count in aged rats tended to be increased as compared with that in young rats (11 weeks old). However, the neutrophils in aged rats exhibited a decline of superoxide anion (O2-) release and phagocytic activity as compared with young rats. The peripheral neutrophil count in aged rats was significantly increased 5-6-fold as many as the control value by rG-CSF treatment, which was accompanied by a significant enhancement of O2- release and of phagocytic activity being restored to normal levels or better. In another series of experiments, we subcutaneously injected rG-CSF or control vehicle into aged mice (24-28 months old) or young mice (8 weeks old) for 7 consecutive days, and evaluated the functions of neutrophils isolated from peritoneal cavity. The peritoneal exudate neutrophils from the aged mice exhibited a decline of phagocytic and chemotactic activity as compared with the young mice. These functions in both young and aged mice were significantly enhanced by rG-CSF-treatment, and these functions in rG-CSF-treated aged mice were restored to a level higher than the level in control young mice. These findings demonstrate that rG-CSF is capable of enhancing granulopoiesis and restoring the age-related decline of neutrophil functions.

Aging↗
PubMed1992

Low susceptibility of nude mice to induction of invasive urinary bladder cancers by N-ethyl-N-(4-hydroxybutyl)nitrosamine.

A time- and dose-dependent study of N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) bladder carcinogenesis was performed in nude mice maintained on tap water containing 0.025% EHBN for 4, 12, and 20 weeks ad libitum. A total of 13 invasive tumors, comprising 11 transitional cell carcinomas (TCCs) (84.6%) and 2 squamous cell carcinomas (SCCs) (15.4%), were found. Compared with previous results for B6C3F1 mice exposed to the same EHBN insult, the numbers of invasive carcinomas induced in nude mice, and especially of SCCs, were low. In order to ascertain whether this difference in cancer incidence between nude and B6C3F1 mice was due to variation in urinary excretion, the metabolism of EHBN was also investigated and compared with that of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). Respective total urinary excretions over 48 hr of N-ethyl-N-(3-carboxypropyl)nitrosamine (ECPN) or N-butyl-N-(3-carboxypropyl)nitrosamine (BCPN), the ultimate carcinogenic species of EHBN or BBN, were 822.4 +/- 41.4 micrograms and 530.4 +/- 81.0 micrograms, respectively, in nude mice, and 800.6 +/- 83.7 micrograms and 407.8 +/- 69.7 micrograms, respectively, in B6C3F1 mice. In conclusion, although it is apparent that nude mice have a low susceptibility to EHBN induction of urinary bladder cancer, this does not appear to be dependent on reduced metabolism to the active form.

Animals↗