The fates of trichothecene mycotoxins, nivalenol and fusarenon-X, in mice

In order to investigate the comparative fates of nivalenol (NIV) and 4-acetyl derivative of NIV (fusarenon-X, FX) in mice, ³H-FX or ³H-NIV was given p.o. to mice. Radioactivity was excreted mainly via the urine in mice given ³H-FX, but mainly via the feces in mice given ³H-NIV. The plasma radioactivity reached a peak at 30 or 60 min after the administration of ³H-FX or ³H-NIV, respectively. The plasma peak level was 5 times higher, and the area under curve (AUC) was 10 times higher, in ³H-FX-administered than ³H-NIV-administered mice. These findings clearly demonstrate that FX is absorbed from the gastrointestinal tract more rapidly and efficiently than NIV. The HPLC profile of radioactivity of acetonitrile extracts of urine and feces indicated that FX is rapidly metabolized to NIV after being absorbed from the gastrointestinal tract. In vitro incubation of tissue homogenates with ³H-FX demonstrated that the liver and kidney are the organs responsible for the FX-to-NIV conversion. Thus this study demonstrated that the higher oral toxicity of FX than NIV that has been observed in mice and rats is due to the efficient absorption of FX than NIV from the gastrointestinal tract, followed by its rapid conversion to NIV by the liver and kidney.     

Linkage guide for rotational alignment during total knee arthroplasty

A linkage guide was devised for use in conjunction with knee arthroplasty instruments to achieve proper component rotation. The femoral component was rotationally aligned to the surgical epicondylar axis using one guide. The other guides were used after all bone surfaces were cut and soft tissue balancing was completed. A Kirschner wire was guided into the proximal tibial aspect parallel to the sagittal plane of the femoral component with the patella in its normal position and the knee in full extension. The wire was used as a reference to determine tibial component rotation. The relative rotational alignment of 21 knees in 19 patients who had undergone cruciate-retaining total knee arthroplasty utilizing this guide was assessed using the modified Eckhoff method. The results of radiographic analysis were compared with those in a control group of 25 knees where the guide was not employed. The external rotation of the femoral component relative to the tibial component was 1.3° ± 2.0° (mean ± SD) in the guided group and 1.1° ± 4.4° in the control group. The relative rotational angle was significantly more consistent using the guide. Implant malrotation can be reduced using our technique.     

Structural changes and cell viability of cultured epithelium after freezing storage

Numerous clinical reports have shown the utility of cultured epithelial grafting in the field of plastic and reconstructive surgery. Recently, freezing storage of the cultured epithelium has been tried and has successfully grafted after thawing. It is clinically convenient if it is possible for cultured epithelium to keep its normal structure and viability. However, few papers have described the structural changes in cultured epithelium after freezing storage. In the present study, the morphological changes and cell viability of cultured mucosal epithelial sheets after freezing were studied in comparison with cultured epidermal sheets. Furthermore, we discuss the effect of storage temperature and cryoprotectants.As a result, there were some structural changes such as vacuolar degeneration in the cultured mucosal sheets using dimethyl sulphoxide (DMSO) as a cryoprotectant. Such changes were more clearly observed at −80°C than at −196°C with DMSO. However, little morphological change was observed in both epithelial sheets cultured with glycerin. The cell viability analysed by flow cytometry showed that more than 62% of the cells kept their viability after freezing storage. These results suggest that the optimum conditions of freezing for cultured epithelium were −196°C storage by slow cooling methods with glycerin as a cryoprotectant.     

Reversal of multidrug resistance by new dihydropyridines with lower calcium antagonistic activity

Summary BS compounds, a series of new dihydropyridines, successfully overcame multidrug resistance in P388/ADR cells in vitro. These agents synergistically potentiated the cytotoxicity of Adriamycin to P388/ADR cells at a concentration of 1–2 M, whereas they showed hardly any synergistic effect in the parental cell line (P388/S) at the same concentration. They inhibited the active drug efflux in P388/ADR cells as well as the binding of [G-³H]-vinblastine to membrane vesicles from P388/ADR, which was increased in resistant P388 cells as compared with parental cells. Besides, unlike the activity of clinically used calcium antagonists, the calcium antagonistic activity associated with BS compounds was very weak: their arterial relaxation activity was <21% of that of verapamil. These data suggest that BS compounds specifically overcome multidrug resistance without the serious hypotensive side effects that accompany the use of verapamil orother calcium antagonists.     

Microarray analysis on Phase II drug metabolizing enzymes expression in pregnant rats after treatment with pregnenolone-16alpha-carbonitrile or phenobarbital

We previously reported the expression profiles of 9 cytochrome P450 isozymes (CYPs) proteins and those of 40 CYPs genes in pregnant rat's liver, placenta and fetal liver after treatment with pregnenolone-16alpha-carbonitrile (PCN) or phenobarbital (PB). This study was carried out focusing on the gene expression profiles of Phase II drug metabolizing enzymes, Glutathione S-transferase isozymes (GSTs) and UDP-glycosyltransferase isozymes (UDPGTs). Fischer 344 (F344) pregnant rats were daily treated intraperitoneally with 50 mg/kg of PCN or 80 mg/kg of PB from 13 to 16 days of gestation (DG). They were sacrificed on 17 DG, and microarray analysis using Affymetrix Rat Expression Array 230 A was performed. Among 16 GSTs genes examined in this study, 7 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 8 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. On the other hand, among 11 UDPGTs genes examined, 5 genes were significantly induced in dam's liver and 3 genes in fetal liver, respectively, in the PCN-group, while 5 genes were significantly induced in dam's liver and 1 gene in fetal liver, respectively, in the PB-group. There were no significant changes in the placenta of all groups. This is the first report of the gene expression profiles of Phase II drug metabolizing enzymes in pregnant rat and fetal livers and placenta after treatment with typical inducers of drug metabolizing enzymes.     

Simulation studies of data classification by artificial neural networks: Potential applications in medical imaging and decision making

Artificial neural networks are being investigated in the field of medical imaging as a means to facilitate pattern recognition and patient classification. In the work reported here, the effects of internal structure and the nature of input data on the performance of neural networks were investigated systematically using computer-simulated data. Network performance was evaluated quantitatively by means of receiver operating characteristic analysis and compared with the performance of an ideal statistical decision maker. We found that the relatively simple neural networks investigated in this study can perform at the level of an ideal decision maker. These simple networks were also found to learn accurately even when the training data are extremely unbalanced with respect to the prevalence of actually positive cases and to differentiate input data patterns by recognizing their unique characteristics.     

Rhythmical contractions in pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats

Rhythmical contractions accompanied by an increase in cytosolic Ca2+ concentrations were produced in ring preparations of endothelium-denuded pulmonary arteries from monocrotaline-treated rats, but not in those from vehicle-treated rats, 2-3 h after a resting tension of 15 mN (150-180% of the initial wall length of the artery) was applied. The rhythmical contractions were abolished by nicardipine and ryanodine. Cyclopiazonic acid reduced the relaxation phase of the rhythmical contractions, finally leading to a sustained contraction. Similarly, apamin caused a sustained contraction, whereas charybdotoxin increased the amplitude of the rhythmical contractions. Glibenclamide had no apparent effects on them. Indomethacin and the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 abolished the rhythmical contractions and reduced the tension, but the thromboxane synthase inhibitor ozagrel had no effect. These results suggest that optimal stretch induces rhythmical contractions in the pulmonary arteries of monocrotaline-induced pulmonary hypertensive rats, to which both Ca2+ influx through voltage-operated Ca2+ channels and Ca2+ release from the endoplasmic reticulum seem to contribute. It is also suggested that small-conductance Ca(2+)-activated K+ channels participate in the relaxation phase of rhythmical contractions. Furthermore, prostaglandin H2 released from nonendothelial cells is likely to play a pivotal role in the induction of rhythmical contractions.     

Protodioscin isolated from fenugreek (Trigonella foenumgraecum L.) induces cell death and morphological change indicative of apoptosis in leukemic cell line H-60, but not in gastric cancer cell line KATO III

Protodioscin (PD) was purified from fenugreek (Trigonella foenumgraecum L.) and identified by Mass, and 1H- and 13C-NMR. The effects of PD on cell viability in human leukemia HL-60 and human stomach cancer KATO III cells were investigated. PD displayed strong growth inhibitory effect against HL-60 cells, but weak growth inhibitory effect on KATO III cells. Morphological change showing apoptotic bodies was observed in the HL-60 cells treated with PD, but not in KATO III cells treated with PD. Flow cytometric analysis showed that the hypodiploid nuclei of HL-60 cells were increased to 75.2, 96.3, and 100% after a 3-day treatment with 2.5, 5, and 10 microM PD, respectively. The fragmentation by PD of DNA to oligonucleosomal-sized fragments, that is a characteristic of apoptosis, was observed to be both concentration- and time-dependent in the HL-60 cells. These findings suggest that growth inhibition by PD of HL-60 cells results from the induction of apoptosis by this compound in HL-60 cells.     

Simple,noninvasive system for measuring the heart rate of avian embryos and hatchlings by means of a piezoelectric film

Using a flexible piezoelectric film, the authors developed a simple system to determine noninvasively the heart rate of chicken embryos and hatchlings. The film was piezoelectric polyvinylidene fluoride (PVDF), which is sensitive enough to detect cardiogenic ballistic movements of the egg (ballistocardiogram (BCG)) and precordial movements of the hatchling attributable to cardiac contractions (apexcardiogram (ACG)). The BCG could be detected, during the second half of incubation, by placing the egg on the PVDF film on a soft substrate. The detected signal was found to be a measure of movement velocity. The ACG could be measured when the hatchling's chest wall made contact with the PVDF film installed in a box in which the hatchling was confined. The heart rate was counted from the lag time of autocorrelation calculated for a certain time segment (e.g. 2s) of the BCG and ACG recordings.     

A stereomicroscopic study of the mastopathic human breast

Summary The stereomicroscopic study of cystic disease of the breast revealed the presence of abnormal ductules near the terminal sites of the original lactiferous ducts. This alteration was the key feature of cystic disease since the involution of abnormal ductules possibly may have induced the stricture of the original duct by increasing fibrosis around the site of duct evolution. The phenomenon could contribute to the creation of cystic dilatation of distal ducts and acini. Multiple large cysts characterizing the morphology of cystic disease may represent the end stage of distended ducts and acini. Prolonged and repeated unbalanced stimulation of hormones could produce progressive and regressive alternations in the same breast. This modifies the original alteration into more pleomorphic and complicated types.

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Stereomikroskopische Studie der durch Mastopathie veränderten menschlichen MammaII. Die peripherische Form der Milchgangsevolution und ihre Beziehung zur Cystenmamma

Zusammenfassung Die stereomikroskopische Untersuchung sog. Cystenmmamen zeigt, daß die Cysten durch Ektasie der sog. Kanälchen-Endäste entstehen. Dagegen werden die Stamm-Milchgänge einer Involution zugeführt. An der Cystenbildung beteiligen sich auch die Acini. Als morphogenetische Reize kommen hormonelle Dysregulatonen in Frage. Durch die unterschiedliche Ausbildung der Kanälchen proliferation einerseits, die Involution sowie Cystenbildung andererseits resultiert ein buntes, wenig einheitliches Bild.

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Clinical Investigator, Veterans Administration Hospital, San Francisco, California, U.S.A., Former Postgraduate Student, Faculty of Medicine, Tokyo Medical and Dental University, Japan.

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This investigation was carried out at the Department of Pathology, Faculty of Medicine, Tokyo Medical and Dental University from 1958 to 1960 and was partially supported by a special research grant of the Japanese Ministry of Education.