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Biomedical subjects

Y Okano

Publications and source records attributed to Y Okano.

At least 55 records · Page 3Linked to original sources
PubMed2000

[Granulocytic sarcoma presenting as an epidural mass with spinal cord compression].

A 73-year-old man was admitted because of back pain and paralysis of the lower extremities. Magnetic resonance imaging of the spine at the Th4-6 level, obtained after gadolinium injection, demonstrated abnormal signal intensity within the Th5-6 vertebral bodies and an extradural soft-tissue mass on the right posterior side of the spinal canal, compressing the thecal sac. The patient underwent prompt decompression with laminectomy, but this was unsuccessful. A biopsy sample of the mass revealed the histological features of granulocytic sarcoma, including diffuse infiltration of numerous cells containing cytoplasmic granules and immunohistochemical positivity for myeloperoxidase. Two months later, a subcutaneous soft-tissue mass appeared at the anterior chest wall, and this was confirmed to be granulocytic sarcoma by microscopic examination. Both of these tumors were radiosensitive, but the patient died of septic shock. Granulocytic sarcoma usually occurs in association with leukemia or other myeloproliferative disorders. However, it is rarely found before leukemia becomes evident in the peripheral blood or bone marrow; only eight such instances have been reported previously.

Aged↗
PubMed1999

Generation of active oxygen species from advanced glycation end-products (AGEs) during ultraviolet light A (UVA) irradiation and a possible mechanism for cell damaging.

Advanced glycation end-products (AGEs) have been reported to be accumulated in dermal skin. However, the role of AGEs in the photoaging of human skin remains unknown, and for this reason, we have examined the interaction between AGEs and ultraviolet A light (UVA) from both the chemical and biological aspects. Previously, we reported that exposing human dermal fibroblasts to UVA in the presence of AGEs that were prepared with bovine serum albumin (BSA) decreased the cell viability due to superoxide anion radical s (.O2(-)) and hydroxyl radicals (.OH) generated by AGEs under UVA irradiation, and active oxygen species are detected with ESR spin-trapping. To identify the active oxygen species in detail and to clarify the cell damaging mechanism, we performed several experiments and the following results were obtained. (1) In ESR spin-trapping, by addition of dimethyl sulfoxide and superoxide dismutase, ESR signals due to .O2(-) -derived DMPO-OOH and .OH-derived DMPO-OH adducts, respectively, were detectable. (2) UVA-irradiated AGEs elevated the lipid peroxide levels in both fibroblasts and liposomes. But the peroxidation in liposomes was inhibited by addition of deferoxamine. (3) Survival of fibroblasts exposed to UVA in the presence of AGEs was elevated by addition of deferoxamine. And finally, (4) survival of fibroblasts was found to be regulated by the level of H2O2. On the basis of these results, we propose a possible mechanism in which AGEs under UVA irradiation generate active oxygen species involving .O2(-), H2O2, and .OH, and the .OH species plays a harmful role in promoting cell damage.

Cell Survival↗
PubMed1999

Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast.

A centrosomal serine/threonine kinase, AIK1(3)/breast tumor amplified kinase/aurora2, which was recently identified as an oncogene, shows high amino acid identity with chromosome segregation kinases, fly Aurora, and yeast Ipl1. Immunohistochemical analyses of invasive ductal adenocarcinomas of the breast revealed that overexpression of AIK1 was observed in 94% of the cases, irrespective of the histopathological type, whereas the protein was not detected in normal ductal and lobular cells. Benign breast lesions including fibrocystic disease and fibroadenoma (epithelial components) displayed weakly detectable AIK1 expression in part of the lesions. This is the first immunohistochemical report of AIK1 expression in primary human breast carcinomas. Although the physiological function(s) of AIK1 kinase during cell division remains to be determined, the markedly high positivity of AIK1 staining in the cancer lesions suggested a possible involvement of its overexpression in the tumorigenesis of some of breast cancer cells.

Anaphase↗
PubMed1999

Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3.

We earlier isolated cDNAs encoding novel human protein kinases AIK and AIK2 sharing high amino acid sequence identities with Drosophila Aurora and Saccharomyces cerevisiae Ipl1 kinases whose mutations cause abnormal chromosome segregation. In the present study, a third human cDNA (AIK3) highly homologous to aurora/IPL1 was isolated, and the nucleotide sequence was determined. This cDNA encodes 309 amino acids with a predicted molecular mass of 35.9 kDa. C-terminal kinase domain of AIK3 protein shares high amino acid sequence identities with those of Aurora/Ipl1 family protein kinases including human AIK, human AIK2, Xenopus pEg2, Drosophila Aurora, and yeast Ipl1, whereas the N-terminal domain of AIK3 protein shares little homology with any other Aurora/Ipl1 family members. AIK3 gene was assigned to human chromosome 19q13.43, which is a frequently deleted or rearranged region in several tumor tissues, by fluorescence in situ hybridization, somatic cell hybrid panel, and radiation hybrid cell panel. Northern blot analyses revealed that AIK3 expression was limited to testis. The expression levels of AIK3 in several cancer cell lines were elevated severalfold compared with normal fibroblasts. In HeLa cells, the endogenous AIK3 protein level is low in G1/S, accumulates during G2/M, and reduces after mitosis. Immunofluorescence studies using a specific antibody have shown that AIK3 is localized to centrosome during mitosis from anaphase to cytokinesis. These results suggest that AIK3 may play a role(s) in centrosome function at later stages of mitosis.

Amino Acid Sequence↗
PubMed1999

Classical galactosemia and mutations at the galactose-1-phosphate uridyl transferase (GALT) gene.

Classical galactosemia is caused by a deficiency in activity of the enzyme galactose-1-phosphate uridyl transferase (GALT), which, in turn, is caused by mutations at the GALT gene. The disorder exhibits considerable allelic heterogeneity and, at the end of 1998, more than 150 different base changes were recorded in 24 different populations and ethnic groups in 15 countries worldwide. The mutations most frequently cited are Q188R, K285N, S135L, and N314D. Q188R is the most common mutation in European populations or in those predominantly of European descent. Overall, it accounts for 60-70% of mutant chromosomes, but there are significant differences in its relative frequency in individual populations. Individuals homoallelic for Q188R tend to have a severe phenotype and this is in keeping with the virtually complete loss of enzyme activity observed in in vitro expression systems. Globally, K285N is rarer, but in many European populations it can be found on 25-40% of mutant chromosomes. It is invariably associated with a severe phenotype. S135L is found almost exclusively in African Americans. In vitro expression results are discrepant, but some individuals carrying S135L appear to exhibit GALT activity in some tissues. Duarte 1 (or Los Angeles) and Duarte 2 (or Duarte) variants carry the same amino acid substitution, N314D, even though D1 is associated with increased erythrocyte GALT activity and D2 with reduced activity. N314D is in linkage disequilibrium with other base changes that differ on the D1 and D2 alleles. N314D does not impair GALT activity in in vitro expression systems. However, there are differences in the abundance of GALT protein in lymphoblastoid cells lines from D2 and D1 individuals. It is unclear whether the specific molecular changes that distinguish the D1 and D2 alleles account for the different activities. The considerable genetic heterogeneity documented to date undoubtedly contributes to the phenotypic heterogeneity that is observed in galactosemia. The additional effects of nonallelic variation and other constitutional factors on phenotypic variability remain to be elucidated.

Alleles↗
PubMed1999

Autoantibodies to RNA polymerases recognize multiple subunits and demonstrate cross-reactivity with RNA polymerase complexes.

OBJECTIVE: To determine the subunit specificity of autoantibody directed to RNA polymerases (RNAP) I, II, and III, which is one of the major autoantibody responses in patients with systemic sclerosis (SSc). METHODS: Thirty-two SSc sera with anti-RNAP antibodies (23 with anti-RNAP I/III, 5 with anti-RNAP I/III and II, and 4 with anti-RNAP II alone) were analyzed by immunoblotting using affinity-purified RNAP and by immunoprecipitation using 35S-labeled cell extracts in which RNAP complexes were dissociated. Antibodies bound to individual RNAP subunits were eluted from preparative immunoblots and were further analyzed by immunoblotting and immunoprecipitation. RESULTS: At least 15 different proteins were bound by antibodies in anti-RNAP-positive SSc sera in various combinations. All 9 sera immunoprecipitating RNAP II and all 28 sera immunoprecipitating RNAP I/III recognized the large subunit proteins of RNAP II and III, respectively. Reactivity to RNAP I large subunits was strongly associated with bright nucleolar staining by indirect immunofluorescence. Affinity-purified antibodies that recognized a 62-kd subunit protein cross-reacted with a 43-kd subunit protein and immunoprecipitated both RNAP I and RNAP III. Antibodies that recognized a 21-kd subunit protein obtained from sera that were positive for anti-RNAP I/III and II antibodies immunoprecipitated both RNAP II and RNAP III. CONCLUSION: Anti-RNAP antibodies recognize multiple subunits of RNAP I, II, and III. Moreover, the results of this study provide the first direct evidence that antibodies that recognize shared subunits of human RNAPs or epitopes present on different human RNAP subunits are responsible for the recognition of multiple RNAPs by SSc sera.

Antibodies, Antinuclear↗
PubMed1999

Ocular effects of adrenomedullin.

The purpose of this study was to determine the expression and effects of adrenomedullin (AM), a novel vasodilator peptide, in the eye. Expression of AM mRNA was examined in the rat iris-ciliary body using reverse transcription-polymerase chain reaction (RT-PCR). In rabbits, intraocular pressure (IOP) was measured periodically after intravitreal injection (20 microl) of AM (10(-7)-10(-4)m) into one eye. In separate groups of rabbits, 30 min after intravitreal injection of either AM-(22-52) (10(-3)m), a specific AM receptor antagonist, or CGRP-(8-37) (10(-3)m), a CGRP1 receptor antagonist, into one eye, AM (10(-6)m) was injected into both eyes, and IOP was measured. Using different rabbits, aqueous protein and cAMP concentrations were determined 6 hr after injection of AM. Expression of AM mRNA was detected in the rat iris-ciliary body. In rabbits, intravitreally administered AM (10(-6)-10(-4)m) profoundly lowered IOP, and the maximum effect was observed at 4-8 h. The ocular hypotensive effect of AM was dose-dependent (10(-7)-10(-4)m). Pretreatment with CGRP-(8-37) did not significantly inhibit the ocular hypotensive effect of AM (10(-6)m), whereas pretreatment with AM-(22-52) completely abolished it. AM (10(-6)m) did not significantly affect aqueous protein concentration. The higher dose of AM (10(-5)m) induced a significant increase in aqueous protein, which was not associated with an increase in the aqueous cAMP content and was significantly inhibited by AM-(22-52) and CGRP-(8-37). These results demonstrate that AM is expressed in the iris-ciliary body and decreases IOP mainly via specific AM receptors, and suggest that AM may play a role in controlling IOP.

Adrenomedullin↗
PubMed1999

Molecular characterization of 6-pyruvoyl-tetrahydropterin synthase deficiency in Japanese patients.

We identified three mutations in four Japanese patients with central type 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency. One missense mutation was a C-to-T transition, resulting in the substitution of Pro by Ser at codon 87 (P87S) in exon 5. Another missense mutation was a G-to-A transition, resulting in the substitution of Asp by Asn at codon 96 (D96N) in exon 5. A splicing mutation was found by skipping of exon 4 on PTPS mRNA analysis, and a G-to-A transition at the third base of codon 81 (E81E) and at the terminal base in exon 4 were detected on genomic PTPS DNA analysis. The E81E mutation affected the splice donor site of exon 4 and caused the splicing error. In COS cell expression analysis, the P87S and D96N mutant constructs revealed, respectively, 52% and 10% of wild-type activity. Patients with P87S/P87S (52%/52% in-vitro PTPS activity) exhibited 0.11 and 0 microU/g hemoglobin [Hb] in erythrocyte PTPS activity (wild-type control: 11-29 microU/gHb) erythrocyte PTPS activity, and the patient with P87S/D96N mutations (52%/10%) had 0.97 microU/gHb in PTPS erythrocyte activity. The PTPS erythrocyte activity did not coincide with the in-vitro PTPS activity based on patient genotype.

Amino Acid Metabolism, Inborn Errors↗
PubMed1999

Molecular characterization of galactokinase deficiency in Japanese patients.

Galactokinase (GALK) deficiency is an autosomal recessive disorder, which causes cataract formation in children not maintained on a lactose-free diet. We characterized the human GALK gene by screening a Japanese genomic DNA phage library, and found that several nucleotides in the 5'-untranslated region and introns 1,2, and 5 in our GALK genomic analysis differed from published data. A 20-bp tandem repeat was found in three places in intron 5, which were considered insertion sequences. We identified five novel mutations in seven unrelated Japanese patients with GALK deficiency. There were three missense mutations and two deletions. All three missense mutations (R256W, T344M, and G349S) occurred at CpG dinucleotides, and the T344M and G349S mutations occurred in the conserved region. The three missense mutations led to a drastic reduction in GALK activity when individual mutant cDNAs were expressed in a mammalian cell system. These findings indicated that these missense mutations caused GALK deficiency. The two deletions, of 410delG and 509-510delGT, occurred at the nucleotide repeats GGGGGG and GTGTGT, respectively, and resulted in in-frame nonsense codons at amino acids 163 and 201. These mutations arose by slipped strand mispairing. All five mutations occurred at hot spots in the CpG dinucleotide for missense mutations and in short direct repeats for deletions. These five mutations in Japanese have not yet been identified in Caucasians. We speculate that the origin of GALK mutations in Japanese is different from that in Caucasians.

Adolescent↗
PubMed1999

Effect of orally active prostacyclin analogue on survival of outpatients with primary pulmonary hypertension.

OBJECTIVES: This study sought to investigate the effect of beraprost sodium (BPS), an orally active prostacyclin analogue, on the survival of outpatients with primary pulmonary hypertension (PPH). BACKGROUND: Continuous intravenous administration of epoprostenol (prostacyclin) has been shown to improve survival in PPH. However, the effect of oral BPS on survival in PPH remains unknown. METHODS: Fifty-eight consecutive patients with PPH who could be discharged after the first diagnostic catheterization for PPH were retrospectively divided into two groups: patients treated with BPS (BPS group, n = 24) and those without BPS (conventional group, n = 34). The baseline demographic and hemodynamic data did not significantly differ between the two. RESULTS: Twenty-seven patients died of cardiopulmonary causes in the conventional group during a mean follow-up period of 44 +/- 45 months. In contrast, only 4 patients died of cardiopulmonary causes in the BPS group during a mean follow-up period of 30 +/- 20 months. In a subsample (n = 15) of patients in the BPS group, mean pulmonary arterial pressure and total pulmonary resistance significantly decreased, respectively, by 13% and 25% during a mean follow-up period of 53 days. Among the variables previously known to be associated with the mortality in PPH, the absence of BPS therapy and the reduced cardiac output were independently related to the mortality by a multivariate Cox proportional hazards regression analysis (both p < 0.05). The Kaplan-Meier survival curves demonstrated that the one-, two- and three-year survival rates for the BPS group were 96%, 86% and 76%, respectively, as compared with 77%, 47% and 44%, respectively, in the conventional group (log-rank test, p < 0.05). CONCLUSIONS: The oral administration of BPS may have beneficial effects on the survival of outpatients with PPH as compared with conventional therapy alone.

Administration, Oral↗
PubMed1999

Ureteropyeloscopy in the diagnosis of patients with upper tract hematuria: an initial clinical study.

BACKGROUND: To study the usefulness and safety of ureteropyeloscopy in the diagnosis of upper tract hematuria of unknown etiology by standard diagnostic methods. METHODS: Fifteen patients with upper tract hematuria of unknown etiology were the subjects of the present study. Prior to ureteropyeloscopy, they underwent standard diagnostic methods, including cystourethroscopy, excretory urography and computed tomography scan. The upper tract (ureter, renal pelvis and calyces) was inspected systematically with a flexible ureteropyeloscope under epidural anesthesia. A biopsy specimen was obtained when neoplasm of a suspicious lesion was seen. Bleeding and hemangiomatous lesions were fulgurated at the time of ureteropyeloscopy. RESULTS: Unilateral gross hematuria was seen in 12 patients. Imaging studies revealed a filling defect in four patients, ureteral stenosis in one patient and nutcracker phenomenon in one patient. Urine cytology was positive in three patients and suspicious in four patients. Results of ureteropyeloscopy were papillary tumor in three patients, whitish encrustation in one patient, redness of the renal pelvis in one patient, bleeding from the renal calyx in two patients, hemangiomatous lesion in one patient, ureteral stenosis in two patients and no abnormalities in five patients. Biopsies were performed in five patients. The pathology results were transitional cell carcinoma in four patients and no abnormality in one patient. Although a ureteral stent catheter was placed in one patient, no serious complications were encountered during or after the procedures. CONCLUSIONS: Ureteropyeloscopy was useful and relatively safe. This endoscopic examination can differentiate insignificant lesions from significant lesions by visual inspection of the lesions, in addition, pathological diagnosis by biopsy specimen can also be performed if deemed necessary. Ureteropyeloscopy is recommended in the diagnosis of upper tract hematuria of unknown etiology.

Adult↗
PubMed1999

Pulmonary artery sarcoma diagnosed using intravascular ultrasound images.

Primary and secondary malignant intravascular tumours of the pulmonary artery occur infrequently and the diagnosis is usually delayed as symptoms and findings from conventional examinations are non-specific. The case is presented of a patient with a pulmonary artery sarcoma, probably arising from ribs resected some years previously, in which intravascular ultrasound (IVUS) provided important diagnostic findings.

Aged↗
PubMed1999

cDNA cloning, characterization, and chromosome mapping of UBE2E3 (alias UbcH9), encoding an N-terminally extended human ubiquitin-conjugating enzyme.

A cDNA encoding a third member of human class III ubiquitin-conjugating enzymes (E2s), UBE2E3, was cloned from a human gastric adenocarcinoma cDNA library. The deduced 207-amino acid protein shares over 94% amino acid identity with the UBC domains of class III E2s, UbcH6, UBE2E2, UbcM2, UbcM3, and UbcD2. But the N-terminal extension exhibited little homology among these, except for UbcM2, which showed 100% identity, and which is thought to be a mouse counterpart. Northern hybridization analysis exhibited a strong 1.9-kb band of UBE2E3 in skeletal muscle. Recombinant fusion protein of GST-UBE2E3 was found to form a thioester bond with ubiquitin (Ub) in an E1-dependent manner, demonstrating that the cDNA encodes a functional E2. In addition, a UBE2E3 mutant of cysteine-145 to serine failed in UBE2E3-Ub complex formation, indicating that the cysteine is essential for E2 function. Using FISH and PCR analysis of radiation hybrid and somatic cell hybrid panels the UBE2E3 gene was mapped to human chromosome 2q32.1 and showed strong linkage to SHGC-8506 (LOD = 11.52) between D2S1302 and D2S364.

Amino Acid Sequence↗
PubMed1999

Association of human leukocyte antigen class II genes with autoantibody profiles, but not with disease susceptibility in Japanese patients with systemic sclerosis.

OBJECT: To examine the role of human leukocyte antigen (HLA) class II genes in the development of systemic sclerosis (SSc) as well as in the clinical and serologic expression of SSc in patients. METHODS: HLA-DRB1, DRB3, DRB4, DQB1, and DPB1 alleles were determined by genotyping; and serum antinuclear antibodies were identified using indirect immunofluorescence, double immunodiffusion and immunoprecipitation. PATIENTS: One hundred and five Japanese patients with SSc and 104 race-matched healthy controls. RESULTS: Frequencies of DRB1 and DQB1 alleles were not different between SSc patients and healthy controls, while DPB1*0901 was marginally increased in SSc patients. In contrast, SSc-related autoantibodies were closely associated with the clinical features. HLA class II genes were detected as follows: anti-DNA topoisomerase I antibody with diffuse cutaneous involvement, pulmonary fibrosis, and DRB1*1502-DQB1*0601-DPB1*0901; anti-U1RNP antibody with overlapping features of lupus and/or myositis and DRB1*0401/*0802-DQB1*0302; and anticentromere antibody with limited cutaneous involvement and DRB1*0101-DQB1*0501-DPB1*0402. In the analysis of the association of HLA class II and the clinical features in SSc patients significant differences were obtained only for the increased frequencies of arthritis and rheumatoid factor in patients with DRB1*0405 compared to those without. CONCLUSION: HLA class II genes strongly influence the production of SSc-related autoantibodies rather than the development of SSc. In addition, SSc is a composite disease of distinctive subsets defined by serum autoantibodies, which have specific clinical and HLA class II associations.

Adolescent↗
PubMed1999

Prognoses of primary pulmonary hypertension and chronic majorvessel thromboembolic pulmonary hypertension determined from cumulative survival curves.

OBJECT: Primary pulmonary hypertension (PPH) has a grave prognosis, and chronic majorvessel thromboembolic pulmonary hypertension (TPH) also has a poor prognosis. The purpose of the study is to elucidate the inherent prognoses of two serious diseases. METHODS: Thirty-two patients with PPH (aged 33+/-15 years, 1SD) and 48 patients with TPH (aged 50+/-14 years, 1SD) were used to determine survival curves using Kaplan and Meier's method from the baseline diagnostic catheterization. Definitive diagnosis was made by cardiac catheterization, ultrasonic echocardiography, ventilation-perfusion lung scanning, and pulmonary angiography. RESULTS: Mean pulmonary artery pressure (PAm) at the initial examination was 56+/-16 (mean+/-1SD) mmHg for patients with PPH and 50+/-13 mmHg for those with TPH, and did not differ significantly between the two groups. Although these two diseases exhibited equally elevated pulmonary arterial pressures, possibly indicative of a poor prognosis, the survival curves obtained from the prospective study for the two diseases were quite different (p<0.001 by generalized Wilcoxon test, p<0.01 by Log-rank test). Mean survival was calculated to be 3.6 years for PPH and 6.8 years for TPH. Patients with TPH had a longer survival than those with PPH, despite the fact that the age at diagnosis of PPH was younger by 17 years on average than that of TPH. CONCLUSION: The inherent prognoses of the two chronic pulmonary hypertensive diseases prior to the introduction of the recently developed new treatment options are shown and likely indicate that the pulmonary vascular lesions in PPH are consistently progressive, while those of TPH are not as progressive.

Adolescent↗
PubMed1999

Increased plasma levels of adrenomedullin in patients with pulmonary hypertension.

Adrenomedullin, a potent hypotensive peptide, reduces blood pressure and pulmonary vascular resistance, and increases pulmonary blood flow. The mRNA for adrenomedullin and its receptor is highly expressed in the lung, suggesting a regulatory role for adrenomedullin in the pulmonary circulation. To investigate the clinical significance of adrenomedullin in patients with pulmonary hypertension, we studied the relationship between plasma levels of adrenomedullin and pulmonary haemodynamics. Venous, arterial and pulmonary arterial blood samples were obtained during cardiac catheterization and plasma levels of adrenomedullin were measured by specific radioimmunoassay in 33 consecutive patients with severe pulmonary hypertension (12 cases of primary pulmonary hypertension, 21 with chronic thromboembolic pulmonary hypertension; age 49+/-16 years, mean pulmonary arterial pressure 50+/-15mmHg). In addition, plasma levels of adrenomedullin were measured before and after acute nitric oxide inhalation. The changes in plasma adrenomedullin during the follow-up period of 10.3+/-4.3 months were also evaluated (n=5). Sixty-two healthy subjects served as the control group. Adrenomedullin was measured in an antecubital vein in the controls. Plasma levels of adrenomedullin were significantly higher in the patients with pulmonary hypertension than in the control subjects (10.1+/-8.7 versus 4.9+/-1.1pmol/l, P<0.01). Plasma levels of adrenomedullin, expressed as their natural logarithm, were significantly correlated with mean right atrial pressure (r=0.71, P<0.01), stroke volume (r=-0.63, P<0.01), total pulmonary resistance (r=0.60, P<0.01), mean pulmonary arterial pressure (r=0.37, P<0.05), and the natural logarithm of plasma atrial natriuretic peptide (r=0. 63, P<0.01). Plasma levels of adrenomedullin did not change significantly after nitric oxide inhalation, but significantly increased in association with the elevation of the total pulmonary resistance during the long-term follow-up period. These results suggest that plasma levels of adrenomedullin increase in proportion to the extent of pulmonary hypertension.

Administration, Inhalation↗
PubMed1998

Sonodynamically-induced cell damage with fluorinated anthracycline derivative, FAD104.

The ultrasonically-induced in vitro cell damaging effect of fluorine-containing anthracycline derivative (FAD104) was investigated. Sarcoma 180 cells suspended in air-saturated PBS were exposed to ultrasound for up to 60 s in the presence and absence of FAD104. The rate of inducing cell damage with ultrasound was doubled with 80 microM FAD104, while no cell damage was observed with FAD104 alone. This enhancement was significantly inhibited by histidine, which may suggest a sonochemical mechanism.

Animals↗