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Biomedical subjects

K Tawara

Publications and source records attributed to K Tawara.

At least 19 recordsLinked to original sources
PubMed2006

Causes of death and renal tubular dysfunction in residents exposed to cadmium in the environment.

OBJECTIVES: To clarify the causes of death of residents with renal tubular dysfunction induced by cadmium (Cd) in the environment. METHODS: A 15 year follow up study was performed with the inhabitants living in the Cd polluted Kakehashi River basin in Japan. Standardised mortality ratios (SMRs) for causes of death, classified by ICD-9, were computed using the person-years method to investigate the excess mortality of subjects with urinary beta2-MG (microglobulin) > or =1000 microg/gCr. Mortality risk analysis was performed using Cox's proportional model to compare mortality between subjects with urinary beta2-MG > or =1000 and <1000 microg/gCr, and to investigate the relationship between the degree of urinary beta2-MG and mortality. RESULTS: Excess mortality due to heart failure and cerebral infarction in both sexes, and nephritis and nephrosis in men, was observed among subjects with urinary beta2-MG > or =1000 microg/gCr. Significant increases in mortality risk for cerebral infarction in men and for malignant neoplasms in women with urinary beta2-MG > or =1000 microg/gCr were observed during the first five year observation period. For nephritis and nephrosis, the mortality risks for men and women with urinary beta2-MG > or =1000 microg/gCr significantly increased over the 15 year observation period. The mortality risks for heart failure and cerebral infarction increased in proportion to the increased urinary beta2-MG in both sexes. Increased mortality risks for nephritis and nephrosis were identified in the subjects with urinary beta2-MG > or =10000 microg/gCr in both sexes. CONCLUSION: Renal tubular dysfunction induced by Cd affected the causes of death, and mortality for heart failure, cerebral infarction, and nephritis and nephrosis was increased among inhabitants living in a Cd polluted area in Japan. In women, cancer mortality may have been increased while Cd pollution was ongoing.

Aged↗
PubMed2002

Effects of maternal exposure to cadmium on pregnancy outcome and breast milk.

OBJECTIVE: The effects of cadmium (Cd) on birth weight have been discussed in the scientific literature. However, investigations on the effects of maternal body burden of Cd on the next generation during pregnancy and lactation have been limited. The relation between maternal exposure to Cd and pregnancy outcome or Cd in breast milk in Japanese mothers was investigated. METHODS: Cd concentrations in urine and colostrum milk samples of 57 mothers were measured by atomic absorption spectrophotometery. The relations between maternal urinary Cd and infant growth, gestational age at birth, and Cd in breast milk were investigated. RESULTS: The rate of perterm deliveries of mothers with higher urinary Cd (> or =2 nmol/mmol creatinine (Cr)) was higher than that of mothers with lower urinary Cd (<2 nmol/mmol Cr). The gestational age was significantly correlated with urinary Cd even after adjustment for maternal age. The height and weight of newborn infants of mothers with higher urinary Cd were significantly lower than those of the newborn infants of mothers with lower urinary Cd, but these decreases were ascribed to early delivery induced by Cd. The Cd in breast milk of mothers with higher urinary Cd was significantly higher than that of mothers with lower urinary Cd. A significant positive correlation was found between maternal urinary Cd and Cd in breast milk. CONCLUSION: Maternal exposure to Cd seems to increase early delivery, which leads to a lower birth weight. Also, the Cd is transferred in part to the next generation through breast milk after birth.

Adult↗
PubMed2000

A case of dermatomyositis associated with mechanic's hand.

A 67-year-old man was referred to the Department of Internal Medicine at Tokyo Medical University with interstitial pneumonia in July 1999. He presented with keratotic plaques on both palsm and on the ventral and lateral sides of his fingers. Erythematous keratosis was observed on the dosal aspect of his fingers and metatarsophalangeal (MP) joints. Edematous erythema was seen on the patient's chest, back, and the extensor surfaces of his arms. Electromyography revealed a myogenic pattern and an increased level of myogenic enzymes was found in the blood. Histological findings of the ventral sides of his fingers showed hyperkeratosis and parakeratosis of the dermal tissue and liquefaction degeneration of the basal layer at the papilla. Based on these findings, the patient was given a diagnosis of dermatomyositis associated with mechanic's hand. A systemic examination confirmed interstitial pneumonia and carcinoma of the duodenal papilla. Mechanic's hand is a type of dermatitis associated with myopathy first reported by Stahl et al. in patients with collagen disease. We report herein the first documented case of mechanic's hand in Asians.

Adenocarcinoma↗
PubMed1994

Reproductive toxicity studies of the new cognition-enhancing agent nefiracetam in rats and rabbits.

The reproductive toxicity of nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl) acetamide, DM-9384, CAS 77191-36-7) was investigated in rats and rabbits. Nefiracetam was administered orally for 9 weeks or more until successful copulation to male rats at doses of up to 480 mg/kg/d. Female rats were treated with nefiracetam at the same doses for more than 2 weeks prior to and in the early stages of pregnancy. No adverse effects on fertility were noted at any dose level. Nefiracetam elicited no evidence of teratogenicity when administered during the fetal organogenesis period to pregnant rats at doses of up to 1000 mg/kg/d, or to pregnant rabbits at doses of up to 270 mg/kg/d. Rat fetuses in the 1000 mg/kg group exhibited decreased body weights, delayed ossification and an increased incidence of skeletal variations such as cervical ribs and shortening of the 13th ribs. Decreased body weight gain and decreased food intake were also noted in rat dams of the 1000 mg/kg group. Nefiracetam showed no adverse effects on postnatal development, behavior or reproductive performance of rat offspring, except for decreased body weight gain in the 1000 mg/kg group. Rabbit fetuses in the 270 mg/kg group exhibited increased skeletal variations, mainly presence of the 13th ribs. Decreased body weight gain and decreased food intake were also noted in rabbit dams of the 270 mg/kg group. In a perinatal and postnatal toxicity study in rats using doses of up to 500 mg/kg, decreased food intakes were noted in dams of the 500 mg/kg group.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1992

Possible direct role of reactive oxygens in the cause of cutaneous phototoxicity induced by five quinolones in mice.

The mechanisms of phototoxicity induced in mice by five quinolone antibacterial agents were investigated using mouse 3T3 fibroblast cells and Balb/c mice. In the in vitro study, the cultured cells were exposed to ultraviolet-A (UVA) in the presence of the five quinolones lomefloxacin, enoxacin, ciprofloxacin, ofloxacin and DR-3355 (the s-isomer of ofloxacin). Cytotoxicity after irradiation was assayed by the neutral red and MTT assay methods, both of which revealed dose-dependent phototoxicity for all five quinolones. Phototoxicity was inhibited by the addition of catalase, and was augmented by the addition of superoxide dismutase. Dimethylthiourea (a hydroxyl radical scavenger) protected against phototoxicity induced by four quinolones, but not against that by enoxacin. These results indicated that superoxide anions, hydrogen peroxide and hydroxyl radicals were generated in solutions of these quinolones under UVA irradiation. In the in vivo study, mice were injected in the auricle with hydrogen peroxide. Ear swelling reactions appeared dose dependently. When irradiated, these reactions were significantly augmented. These data suggested that cutaneous phototoxicity in Balb/c mice is initiated by the generation of reactive oxygens in the target tissue, especially of hydroxyl radicals.

3T3 Cells↗
PubMed1992

Possible reasons for differences in phototoxic potential of a 5 quinolone antibacterial agents: generation of toxic oxygen.

The reason for the differences in phototoxic potential between the 5 quinolone antibacterial agents lomefloxacin, enoxacin, ciprofloxacin, ofloxacin and DR-3355 (the s-isomer of ofloxacin) in mice was investigated. Superoxide anion, hydrogen peroxide (H2O2), and bleaching of p-nitrosodimethylaniline (B-NDMA) were detected in quinolone solutions during irradiation with ultraviolet-A (UVA). Apparent levels of H2O2 and the B-NDMA per mole of quinolone paralled the phototoxic potentials in the mice. The N-NDMA induced by quinolones and UVA was inhibited partially by treatment with D-mannitol and dimethylsulfoxide, and also with diethylenetriamine-pentaaceticacid (DTPA), suggesting that Haber-Weiss and Fenton reactions occurred. UVA concentration-dependently increased the level of the B-NMDA in H2O2 solution and the swelling in the ear pretreated by intra-auricular injection of H2O2. Both augmentations were inhibited by DTPA or DMSO. The swelling induced by the 5 quinolones and UVA was completely inhibited by pretreatment with dimethylsulfoxide. Oxygen consumption was detectable during the photodegradation, and increased with time. These results showed that the phototoxic potentials of the 5 quinolones were probably related to the amounts of toxic oxygens generated in the target cells during irradiation.

Animals↗
PubMed1992

Interaction of the new quinolone antibacterial agent levofloxacin with fenbufen in mice.

The interaction of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- piperazinyl)-7-oxo-7H-pyrido[1,2,3-de] [1,4]benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) with fenbufen, a nonsteroidal anti-inflammatory agent, in mice was assessed by convulsive seizure and subsequent death in comparison with that of other new quinolones such as DR-3354 (the R-(+)-isomer of ofloxacin), ofloxacin, norfloxacin, enoxacin and ciprofloxacin. Although treatment with each quinolone or fenbufen alone at a dosage level tested in mice showed no changes, coadministration of a large dose of all quinolones and fenbufen caused convulsant death. When compared with the severity of this interaction, it was in the order of enoxacin greater than norfloxacin greater than ciprofloxacin greater than DR-3354 greater than ofloxacin greater than or equal to DR-3355 under these experimental conditions.

Animals↗
PubMed1991

Effect of L-arginine on the retention of macrophage tumoricidal activity.

It has been reported that the tumoricidal activity of macrophages (M phi) depends on L-arginine and that L-arginine metabolites such as reactive nitrogen intermediates alter M phi physical capacities. The aim of this report is to investigate the dose-related effect of L-arginine on the expression and retention of M phi tumoricidal activity. Cytotoxicity of M phi activated by IFN-gamma plus LPS was detected in the presence of about 0.1 mM or more of L-arginine. This paralleled the NO2- production in the presence, but not in the absence, of L-arginine. On the other hand, activated M phi were destined to die and lost their tumoricidal activity with time in the presence of 0.3 mM or more L-arginine. They retained, however, considerable activity in the absence or presence of 0.15 mM L-arginine. This retention of M phi cytotoxicity was longer when M phi were preactivated by 100 ng/ml than 10 ng/ml of LPS in combination with IFN-gamma. Addition of indomethacin, an inhibitor of prostaglandin production, did not prevent the decay of M phi cytotoxicity but rather facilitated it even in the absence of L-arginine. Regardless of indomethacin, consecutive stimulation with LPS or LPS plus IFN-gamma during culture was effective in maintaining the tumoricidal activity at a high level. In addition, we found that M phi which had lost tumoricidal activity during culture in L-arginine deficient medium could be reactivated by LPS to attack tumor target cells.

Animals↗
PubMed1991

Macrophage-activating factor extracted from mycoplasmas.

Mycoplasmas (M. gallisepticum, chicken mycoplasmas), in concert with interferon gamma (IFN gamma), were effective in activating macrophages (M theta) to be tumoricidal. The M theta-activating capacity of mycoplasmas was maintained after treatment with heat. 0.1 M NaOH, 1 M HCl, or trypsin. M theta-activating factor was extracted from mycoplasmas with chloroform/methanol and water (Mf-B). Mf-B was also effective in activating M theta in the presence of IFN gamma. The threshold dose of Mf-B for M theta of ordinary C3H/He mice and that for those of C3H/HeJ mice, the latter being known to be low responders to bacterial lipopolysaccharide, were actually the same. This seems to indicate that the effectiveness of Mf-B was not attributable to possibly contaminating lipopolysaccharides, and that the pathway of activity of Mf-B is different from that of lipopolysaccharides. Since the M theta-activating principle was only a very small part of Mf-B, we have not yet succeeded in identifying it, but there was no evidence that it was protein, nucleic acid, sugar, or lipid. The cytotoxicity of M theta activated by Mf-B plus IFN gamma was dependent on L-arginine in the culture, suggesting that arginine metabolites are involved in M theta cytotoxicity. Mf-B induced a small amount of tumor necrosis factor in M theta, and this induction was markedly enhanced by IFN gamma.

Animals↗
PubMed1991

Important role of oxygen metabolites in quinolone antibacterial agent-induced cutaneous phototoxicity in mice.

We investigated whether or not the generation of reactive oxygens and toxic photoproducts participated in the cutaneous phototoxicity mechanisms induced by the quinolone derivatives, ofloxacin (OFLX), enoxacin, lomefloxacin, ciprofloxacin and DR-3355 (the s-isomer of OFLX) in a mouse model. Pretreatment of Balb/c mice with allopurinol, soybean trypsin inhibitor, catalase and beta-carotene gave significant protection against ear swelling reactions induced by oral administration of quinolones and following ultraviolet-A (UVA) irradiation. Pretreatment with diethyldithiocarbamate augmented the swelling. No swelling was observed with direct injection into the auricle of UVA-pretreated photoproducts of the quinolones. These results showed that cutaneous phototoxicity did not depend on the generation of toxic photoproducts and suggested that oxygen metabolites generated in the xanthine oxidase pathway participated in the toxicity.

4-Quinolones↗
PubMed1991

Quinolone antibacterial-agent-induced cutaneous phototoxicity: ear swelling reactions in Balb/c mice.

The phototoxic potentials of quinolone derivatives and the possibility of free radical contribution to their phototoxicity were investigated by measuring increments in ear thickness. Balb/c mice, fasted overnight, were orally administered ofloxacin (OFLX), lomefloxacin (LMFX), enoxacin (ENX), ciprofloxacin (CPFX) and DR-3355 (the s-isomer of OFLX), and immediately exposed to ultraviolet-A light (UVA: 320-400 nm) for 4 h (21.6 joules/cm2). Measurement of ear thickness was carried out 0, 24 and 48 h after the end of irradiation. The time-course profiles of ear thickness varied with both the doses and the quinolone used, but linear dose-response curves were obtained from the data 24 h after irradiation ended. The 50% ear thickness increment-inducing doses of LMFX, ENX, OFLX, CPFX and DR-3355 were calculated as 24.8, 81.9, 428.0, 457.9 and 526.6 mg/kg, respectively. The phototoxic potential of these quinolones coincided with the data obtained previously by measuring the incidence of erythema on the ears. Pretreatment with butylated hydroxtoluene, a free radical scavenger, almost completely prevented all swelling reactions induced by the quinolones. These results suggest that the degree of phototoxicity induced by the quinolones used could depend on the balance between the generation of free radicals and the effectiveness of the defense systems against toxic radicals.

4-Quinolones↗
PubMed1991

Alteration of physiological activity of activated macrophages through L-arginine metabolism.

Our aim in this study was to define the effect of L-arginine on macrophages (M phi) in relation to the decay of tumoricidal activity of activated M phi. We found that the activated M phi retained their cytotoxicity when cultured in L-arginine-deficient medium but not in conventional medium. Such a decline of tumoricidal activity was associated with increase of glucose consumption and concomitant lactate production, resulting in M phi death. Addition of glucose to the culture medium of activated M phi appeared to cause only a slight delay of the decrease of tumoricidal activity and M phi death. These events were also coincident with a decrease of electron transport activity in mitochondria. Cytological observation by electron microscopy clearly showed the structural alteration or destruction of mitochondria, which preceded the changes of other physiological and functional activities. These results demonstrate that the L-arginine-dependent cytolytic activity against tumor target cells also impairs M phi functions and ultimately induces M phi death, which is primarily mediated by the inhibition of mitochondrial activity.

Animals↗
PubMed1990

Phototoxic potential of quinolone antibacterial agents in Balb/c mice.

The phototoxic potentials of quinolone antibacterial agents were investigated in Balb/c strain mice. The mice were orally administered nalidixic acid (NA), enoxacin (ENX), ofloxacin (OFLX), ciprofloxacin (CPFX), lomefloxacin (LMFX) and DR-3355 (s-isomer of OFLX), and immediately exposed to ultraviolet-A (UVA) for 4 h (21.6 joules/cm2). The ears were examined for overt damage, as a major phototoxic parameter, 0, 24 and 48 h after irradiation ended. At doses of 200 mg/kg, LMFX, NA and ENX caused marked cutaneous phototoxic reactions on the ears, whereas CPFX, OFLX and DR-3355 caused none. At 800 mg/kg, however, CPFX, OFLX and DR-3355 also caused phototoxic reactions on the ears. These phototoxic changes were characterized grossly by erythema, and histopathologically by edema and infiltration of inflammatory cells, especially neutrophils, into the connective tissue surrounding the cartilage. The 50% erythema-inducing doses of LMFX, ENX, NA, OFLX, DR-3355 and CPFX were calculated at 19, 102, 143, 553, 619 and 741 mg/kg, respectively. Thus, the phototoxic potencies of the quinolones tested were: LMFX greater than ENX, NA greater than OFLX, DR-3355, CPFX.

4-Quinolones↗
PubMed1990

Isolation of cepafungins I, II and III from Pseudomonas species.

New acylpeptide antibiotics named cepafungins I, II and III were isolated from the culture broth of a strain identified as Pseudomonas sp. These antibiotics are neutral substances, soluble in aqueous alcohols and dimethyl sulfoxide, and show UV maxima at 260.5 nm. The IR spectra indicated these to be peptides. Molecular formulas C28H46N4O6, C27H44N4O6 and C26H42N4O6 for cepafungins I, II and III were indicated by elemental analysis and SI-MS. Cepafungins exhibited inhibitory activity against yeast and fungi, and antitumor activity against P388 leukemia in mice.

Animals↗
PubMed1989

Studies on experimental conditions for detecting phototoxic potentials of drugs in Balb/c mice.

This study was designed to establish a procedure for detecting the phototoxicity of drugs in an animal model. Experimental conditions in relation to intensity distribution of ultraviolet-A (UVA), duration of irradiation, and suitable region for irradiation were investigated. One black light gave a wide constant-energy region when the distance from the light source to the irradiation area was 15 cm. The intensity distribution of a bank of 10 black lights formed a pattern like the contour map of a truncated cone in the irradiation area. In phototoxic studies, Balb/c strain mice were orally administered chlorpromazine and nalidixic acid, clinically known as photosensitizers, and were immediately exposed to UVA irradiation. The optimal irradiation time was 4 hours at an energy of 20 Joules/cm2, which with a high frequency caused erythema on the surface of the ears in the central area, which received about 1.5 mW/sec.cm2, but no reaction occurred in the surrounding area (0.5-0.8 mW/sec.cm2). These results indicate that it is important to select a suitable irradiation area and sufficient intensity of irradiation in order to determine whether a drug has phototoxic potential.

Animals↗
PubMed1989

Isolation of CB-25-I, an antifungal antibiotic, from Serratia plymuthica.

A new antifungal antibiotic, CB-25-I, was isolated from the culture broth of a strain of Serratia plymuthica. The antibiotic, a water-soluble dipeptide, is structurally related to Sch 37137 and A 19009, both produced by strains of Actinomycetales. The antibiotic exhibits inhibitory activity against Candida albicans in YNB medium (a synthetic medium), but the activity is significantly reduced in Sabouroud dextrose medium.

Amino Acids↗