Ganglioglioma originating in the cerebellum with a large cyst--a case report and review of the literature.

Here we report a rare case of cerebellar ganglioglioma accompanied by a large cyst, and present a review of the reported 28 cases with cerebellar ganglioglioma. An otherwise healthy 46-year-old woman complained of gradual headache and truncal ataxia. MRI revealed a huge cystic lesion with a mural nodule in the left cerebellar hemisphere. The tumor was resected totally. Histologically, it was composed of neuronal and glial elements, and was accordingly diagnosed as ganglioglioma.

Partial purification of estrogen-dependent peroxidase of rat uterus and comparison of the properties with those of other animal peroxidases.

An attempt was made to solubilize a peroxidase from the uterine tissue of estrogen-primed rats using various detergents, and the best result was obtained by incubation with 4% cetyltrimethylammonium bromide at 37 degrees C for 60 min. The solubilized material was then dialyzed and subjected to gel filtration on Sephacryl S-200 followed by CM-cellulose chromatography, resulting in a 50-250-fold increase in specific activity over the detergent extract. Some properties of the partially purified uterine tissue peroxidase were studied in comparison with those of other animal peroxidases. The absorption spectra, molecular weight, and isoelectric point are very similar to those of lactoperoxidase. However, the oxidation rates of various hydrogen donor substrates by the uterine peroxidase were not parallel to those of lactoperoxidase and other animal peroxidases and the affinities for cyanide and azide of these enzymes were somewhat different from each other. The uterine peroxidase was inhibited by histidine and excess hydrogen peroxide competitively with respect to guaiacol, suggesting an important role of an amino acid residue in the protein moiety.

Spectroscopic and kinetic properties of the estrogen-induced peroxidase in rat uterine fluid.

Uterine fluid was collected from estrogen-primed rats which had each previously been subjected to an operation to close the cervical junction of the uterus. Starting from the uterine fluid, uterine fluid peroxidase was purified by carboxymethyl cellulose column chromatography followed by gel filtration on Sephacryl S-200. The purity of the enzyme preparation, as estimated by microelectrophoresis on polyacrylamide gel, was found to be 70-95%. Absorption spectra of the peroxidase and its derivatives resembled those of lactoperoxidase. The pyridine hemochromogen spectrum of the enzyme was also very similar to that of lactoperoxidase. The apparent molecular weight of the enzyme was estimated to be 90,000, being similar to that of lactoperoxidase (78,000). Uterine fluid peroxidase has, however, distinctly different properties from lactoperoxidase, for example, in substrate specificity, pH optimum, inhibition by excess hydrogen peroxide, and isoelectric point.

An assessment of antigenic potential of beta-lactam antibiotics, low molecular weight drugs, using guinea pig models.

Allergic reactions are among the common adverse effects in humans. However, it is widely assumed that there are practically no reliable animal models for preclinical tests of low-molecular weight drugs that are available to predict such reactions. This study was designed to compare the detecting ability of test methods for antigenic potential of eight beta-lactam antibiotics with which allergic outcome has been reported in humans. The tests included active systemic anaphylaxis (ASA), delayed type skin reaction (DSR), maximization test (GPMT) in guinea pigs sensitized with antibiotics emulsified with Freund's complete adjuvant, passive cutaneous anaphylaxis (PCA) and enzyme-linked immunosorbent assay (ELISA) as serological tests. PCA and ELISA though using protein-conjugates as detecting antigens, especially ELISA, showed positive reactions with relatively high incidence. On the other hand, GPMT was the most sensitive method to detect antigenic potential of antibiotics despite the use of antibiotics alone for sensitizing and challenging phases. It is suggested that GPMT can be considered the most reliable method in preclinical testing.

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.

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.

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.

[Local spinal cord glucose utilization and extracellular potassium activity changes after spinal cord injury in rats].

Spinal microenvironment and metabolic alterations after experimental contusional injury of the spinal cord were evaluated in the same Wistar rats. Severe spinal cord injury was made under light GOF anesthesia with a 10 g weight drop onto the exposed Th-8 spinal cord from a 10 cm height and then halothane was ceased. The author studied extracellular potassium activity ([K+]e) and DC potential for 2 hours after paraplegic spinal cord injury in conscious rats. Furthermore, at 2 hours after cord injury, local spinal cord glucose utilization (1-SCGU) was measured with quantitative autoradiographic 2-[14C] deoxy-glucose method (Sokoloff et al.). [K+]e in injured spinal cords was 59 +/- 5 (mean +/- S.E.M.) mEq at 10 min after injury and was cleared with an exponential half-life of 1 hour. At 2 hours after injury [K+]e was still high with a value of 16 +/- 1 mEq compared with 4 mEq of control animals. DC potential changes was a mirror image of that of [K+]e. DC potential changed by a mean of 10.7 mV positively from 10 min. to 2 hours after injury. 1-SCGU at the impact site was extremely low in both white and gray matters. At 6mm rostral from the impact center 1-SCGU was remarkably reduced in the gray matter, and in the lateral white matter. But at 3 mm rostral 1-SCGU was well preserved. And at 20 mm rostral there was no difference in 1-SCGU with control animals. Massive potassium efflux from the injured spinal cord to the adjacent spinal segment was clarified at this experiment.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of the cortical subarachnoid hemorrhage on cerebral glucose metabolism].

Neurological deficits following human subarachnoid hemorrhage (SAH) have been related to the cerebral arterial spasm and the increase in intracranial pressure (ICP) secondary to the development of hydrocephalus. Metabolic depression in experiment study was thought as resulting from brain stem dysfunction. On the other hand, some reports have shown no relationship between vasospasm and neurological abnormalities. The mechanism of cerebral metabolism depression after SAH remains unclear. The effect of blood in the cortical subarachnoid space on the cerebral metabolism has not been known well. To investigate this effect, a new cortical SAH model was developed using rat and local cerebral glucose utilization (LCGU) after production of SAH was measured. A cortical SAH model: a small burr hole was made on the left parietal bone and the arachnoid membrane was pierced with a tapered glass-needle 60 mu tip in diameter. Fresh autologous non-heparinized arterial blood 0.04 ml was injected into subarachnoid space within 60 seconds through that needle. The blood extended over the left cerebral cortical surface with thin subarachnoid hematoma on the parietal cortex, but did not extend on the right hemisphere and the basal cistern. The increase in ICP during production of SAH was minimal, mean value of 7.2 mmHg and ICP slowly returned to the basal level within 30 minutes. Rats were divided into 3 groups; rats 2 hours (SAH-2h, n = 7) and 48 hours (SAH-48h, n = 7) after production of SAH and rats 2hours after 0.04 ml saline injection for control (Control, n = 7). LCGU was studied according to the methods developed by Sokoloff.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Phototoxic potential of the new quinolone antibacterial agent levofloxacin in mice.

The phototoxic potential of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4- methyl-1-piperazyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6- carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 100986-85-4) was evaluated by the mice ear swelling reaction. Results were compared with those for enoxacin (ENX). Mice were orally administered DR-3355 or ENX and immediately exposed to ultraviolet-A for 4 h. Phototoxicity was determined by measuring ear thickness developing 24 h after irradiation. DR-3355 provided no changes in the ear at 200 mg/kg, but caused ear swelling at 800 mg/kg. ENX caused severe phototoxicity in a dose dependent manner from 50 mg/kg. These data suggest that DR-3355 has minor phototoxic potential, but is approximately 4-fold less toxic than ENX in these experimental conditions.

Involvement of cytoplasmic serine proteinase and CPP32 subfamily in the molecular machinery of caspase 3 activation during Fas-mediated apoptosis.

On stimulation by the Fas ligand, the death receptor, Fas, initiates a signal leading to apoptotic cell death. Fas plays an important role in physiological cell death and is closely involved in various disease states. Recent investigations have shown that caspase 3 plays a dominant role in the process of Fas-mediated apoptosis. In the present study, we investigated the molecular machinery of caspase 3 activation in Fas-mediated apoptosis. The results showed that Fas-mediated apoptosis was accompanied by caspase 3 activation, and both Fas-mediated apoptosis and caspase 3 activation were prevented by a serine proteinase inhibitor. In addition, the serine proteinase inhibitor also prevented the caspase 3 activation in cytoplasts, and the specific activation of serineproteinase was encountered in only cytoplasmic proteins. These results suggest that cytoplasmic serineproteinase plays an important role in caspase 3 activation. Interestingly, caspase 3 was cleaved at p3 site immediately after Fas Ab stimulation, and the cleavage at p17 site became detectable later. We also found that among tested proteinases only Staphylococcus aureus V8 serineproteinase initiated caspase 3 activation and specifically cleaved at p3 site. These results strongly suggest that a cytoplasmic S. aureus V8-like serine proteinase is closely involved in caspase 3 activation.

Stimulation of prostaglandin production by quinolone phototoxicity in Balb/c 3T3 mouse fibroblast cells in vitro.

Sparfloxacin (SPFX) and levofloxacin (LVFX) with ultraviolet-A (UVA) irradiation have been reported to induce skin inflammation due to phototoxicity in Balb/c mice. We examined the production of arachidonic acid metabolites induced by quinolone phototoxicity in Balb/c 3T3 mouse fibroblast cells in vitro. The cells were simultaneously treated with SPFX or LVFX at 1, 10, or 100 microM and UVA irradiation for 5 min (0.5 J/cm2). They were then cultured in quinolone-free medium for 24 hr, and the concentrations of prostaglandin E2 (PGE2), 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha), and leukotriene B4 (LTB4) in the incubation medium were measured. Furthermore, the effect of quinolone photoproducts on the production of the inflammatory mediators and that of indomethacin on PGE2 level were also examined. Treatment with SPFX at 100 microM plus UVA irradiation markedly increased levels of PGE2 and 6-keto-PGF1 alpha, but not that of LTB4. SPFX or LVFX alone at up to 100 microM, 10 microM SPFX, or 100 microM LVFX, or less plus UVA irradiation, or UVA-preirradiated quinolone up to 100 microM had no effect. Indomethacin even at 0.1 microM completely inhibited the PGE2 elevation induced by 100 microM SPFX with UVA. These results suggest that PGs released from dermal fibroblasts in the simultaneous presence of quinolone and UVA could contribute in part to the development of skin inflammation in vivo.

Antigenicity study of the new cognition-enhancing agent nefiracetam.

The potential antigenicity of the new cognition-enhancing agent nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxo-1-pyrrolidinyl)acetamide, DM-9384, CAS 77191-36-7) was investigated by tests for passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA) and skin reaction in mice and guinea pigs. Mice were sensitized with nefiracetam (10-100 micrograms/animal) or nefiracetam-egg albumin (OA) mixture (10 micrograms/animal). No IgE antibodies to nefiracetam were detected in plasmas obtained from nefiracetam and nefiracetam-OA sensitized mice, indicating that nefiracetam has no immunogenicity or antigenicity eliciting potential. Guinea pigs were sensitized with nefiracetam (20-100 or 20 mg/kg) or nefiracetam-OA (2 mg/kg). No antibodies to nefiracetam were detected in the sera obtained from sensitized guinea pigs by PCA. Neither SA nor skin reaction was observed in the sensitized guinea pigs after the injection of challenge. These results suggest that nefiracetam possesses no antigenicity in mice and guinea pigs.

Antigenicity of the new quinolone antibacterial agent levofloxacin.

An antigenicity study of a new quinolone antibacterial agent, (-)-(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 (lefovloxacin, DR-3355, CAS 100986-85-4), was carried out in mice, guinea pigs and rabbits with passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA) and enzyme linked immunosorbent assay (ELISA). Mice were sensitized with DR-3355 (1-100 mg/kg) or DR-3355-ovalbumin (OA) conjugate (DR-3355-OA; 500 micrograms/kg). No IgE antibodies to DR-3355 were detected in the sera obtained from the DR-3355-sensitized mice, indicating that DR-3355 has no immunogenicity in mice. By using DR-3355-OA as a sensitizing antigen, DR-3355-specific IgE was produced successfully in 7 out of 10 sera, and 4 sera showed positive responses in 24-h PCA on intravenous injection of DR-3355 (40 mg/kg). These responses disappeared on challenge with a dose of 2.5 mg/kg. Guinea pigs or rabbits were sensitized with DR-3355 (2-100 or 2-20 mg/kg) or DR-3355-OA (2 mg/kg). No SA was observed in the sensitized guinea pigs after the intravenous injection of DR-3355 (40 mg/kg). No antibodies to DR-3355 were detected in the sera obtained from the sensitized guinea pigs and rabbits by PCA or ELISA. These results suggest that DR-3355 may not possess antigenicity in guinea pigs and rabbits. On the other hand, the results of PCA in mice suggest that DR-3355 may have eliciting antigenicity potential.

Antigenicity study of muroctasin.

Antigenicity study of N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysi++ + ne (MDP-Lys(L18), muroctasin) was carried out in mice, guinea pigs and rabbits with passive cutaneous anaphylaxis (PCA), systemic anaphylaxis (SA), Arthus and delayed skin reaction and enzyme-linked immunosorbent assay (ELISA). Mice were sensitized intraperitoneally, twice at 3-week intervals, with MDP-Lys(L18) (40, 400 or 4000 micrograms/kg) or MDP-Lys(L18)-ovalbumin (OA) conjugate (500 micrograms/kg) in alumina gel. No IgE antibodies to MDP-Lys(L18) were detected in the sera obtained from the sensitized mice by 24-h PCA in rat. Guinea pigs were sensitized subcutaneously with MDP-Lys(L18) (4, 40 or 400 micrograms/kg) or MDP-Lys(L18)-OA (2 mg/kg) emulsified in Freund's complete and incomplete adjuvant, 3 times at 2-week intervals. No SA was observed in the sensitized animals after the intravenous injection of MDP-Lys(L18) (1 mg/kg). Rabbits were sensitized subcutaneously with MDP-Lys(L18) (2 or 20 micrograms/kg) or MDP-Lys(L18)-OA (2 mg/kg) emulsified in Freund's incomplete adjuvant, 3 times at 2-week intervals. Neither Arthus nor delayed skin reaction was observed in the sensitized animals after the intradermal injection of MDP-Lys(L18) (2 micrograms/site). Although antibodies to MDP-Lys(L18) were not detected in MDP-Lys(L18) sensitized animals, the antibodies were detected in two out of 9 guinea pigs and all of the rabbits in the MDP-Lys(L18)-OA sensitized groups by 4-h PCA after the intravenous injection of MDP-Lys(L18) (1 mg/kg). These results suggest that MDP-Lys(L18) may possess antigenic potential by PCA reaction in guinea pigs.

Sequential operation of ceramide synthesis and ICE cascade in CPT-11-initiated apoptotic death signaling.

The chemotherapeutic agent CPT-11 induced apoptotic cell death in mouse fibroblast 4B1 cells. To examine the intracellular apoptotic death signal initiated by CPT-11, ceramide synthesis and the ICE cascade were analyzed. CPT-11-initiated cytolytic activity was prevented by both caspase inhibitors YVAD-CHO and DEVD-CHO, or ceramide synthesis inhibitor fumonisin B1, and accelerated by sphingomyelin, suggesting the direct involvement of ceramide synthesis and the interleukin 1-beta converting enzyme (ICE) cascade. In addition, apoptosis was induced by both native and synthesized ceramide and prevented by YVAD-CHO and DEVD-CHO, suggesting the possible involvement of ceramide in ICE cascade operation. To directly demonstrate whether ceramide synthesis operates the ICE cascade, proteolytic activity of ICE- or CPP32-like proteinase was analyzed. ICE-like proteinase activity was prevented by fumonisin B1 and YVAD-CHO, but not by DEVD-CHO. In contrast, fumonisin B1, YVAD-CHO, and DEVD-CHO all prevented CPP32-like proteinase activity. These results suggest that ceramide synthesis acts as a dominant regulator in CPT-11-initiated death signaling and sequentially operates the ICE cascade.

Phototoxic lesions induced by quinolone antibacterial agents in auricular skin and retina of albino mice.

The phototoxic effects of quinolone antimicrobial agents on mouse auricular skin and retina were examined histologically. Sparfloxacin at 50 or 100 mg/kg, which alone causes no histologic change, was orally administered to albino Balb/c mice, which were irradiated with ultraviolet A for 4 hr immediately after administration. In the auricle, degeneration of basal epidermal cells was sporadically observed at 2 hr (during the irradiation). Foci of slight edema with degenerated fibroblasts were seen in the dermis at 4 hr. Edema and neutrophil infiltration in the dermis became severe up to 96 hr. Initial changes in the retina were observed at 2 hr. Vacuolation of the photoreceptor segments (particularly the inner segment) was occasionally associated with swelling of retinal pigment epithelial cells. The segments became disorganized with time, and the outer nuclear layer showed reduced cellularity. The segments and layer were partially thinned and lost 96 hr later. Enoxacin at 400 and 800 mg/kg induced similar lesions to those of sparfloxacin. Levofloxacin caused similar lesions in the auricle but no change in the retina. The combination of oral administration of quinolone and ultraviolet A irradiation, which never caused apparent morphological changes alone, was shown to be able to induce phototoxic lesions in albino mice. Therefore, this method is thought to be useful to examine morphological changes caused by quinolone phototoxicity.