3,3′,4,4′,5-Pentachlorobiphenyl Inhibits Drug Efflux Through P-Glycoprotein in KB-3 Cells Expressing Mutant Human P-Glycoprotein

The effects on the drug efflux of 3,3′,4,4′,5-pentachlorobiphenyl (PCB-126), the most toxic of all coplanar polychlorinated biphenyls (Co-PCBs), were examined in KB-3 cells expressing human wild-type and mutant P-glycoprotein in which the 61st amino acid was substituted for serine or phenylalanine (KB3-Phe(61)). In the cells expressing P-glycoproteins, accumulations of vinblastine and colchicine decreased form 85% to 92% and from 62% to 91%, respectively, and the drug tolerances for these chemicals were increased. In KB3-Phe(61), the decreases in drug accumulation were inhibited by adding PCB-126 in a way similar to that with cyclosporine A: by adding 1 μM PCB-126, the accumulations of vinblastine and colchicine increased up to 3.3- and 2.3-fold, respectively. It is suggested that PCB-126 decreased the drug efflux by inhibiting the P-glycoprotein in KB3-Phe(61). Since there were various P-glycoproteins and many congeners of Co-PCBs, this inhibition has to be considered a new cause of the toxic effects of Co-PCBs

3,3 ,4,4 ,5-Pentachlorobiphenyl Inhibits Drug Efflux Through P-Glycoprotein in KB-3 Cells Expressing Mutant Human P-Glycoprotein

The effects on the drug efflux o

Surgery for Irradiation Damage to the Digestive Tract.

The surgical outcome of radiation injury to the gut was evaluated on the basis of clinical experience. The main affected gut was the rectum in frequency. In most cases, colostomy was selected and the affected gut was left as it was. Some suffered from bleeding episode and 4 had carcinoma arising from radiation injury. In conclusion, early resection of affected guts associated with clinical symptoms is recommended as the treatment of radiation-injured gut

The Validily of Tracheal Surgery for the Aged

Surgery for tracheal stenotic lesions in older patients over age 70 was evaluated in comparison with younger patients under age 69 on the basis of our clinical experience. The causes of tracheal lesions were mainly malignant diseases in spite of varying variety of etiology in the younger patients. The outcome of surgical treatment in the older ones was not inferior to that in the younger ones as far as postoperative complications were prevented. In conclusion, it is emphasized that the surgical treatment of choice is essential for palliation of symptoms and expectance of high quality of life

En Bloc Resection for Lung Cancer Involving Left Atrium

En bloc resections for patients with left atrium involved by lung cancers were evaluated in the 8 patients in terms of the operative procedure, the indication and the outcome. In one patient, application of extracorporeal circulation was accomplished to perform a complete resection and also to permit patch plasty to compensate volume diminution. En bloc resection on extracorporeal circulation is recommended for patients with limited cancer extension of squamous cell carcinomas without nodal involvement. In addition, emphasis has been placed in the genesis of double cancer in follow-up study according to improvement of surgical result in reflection of susceptibility to carcinomas in other organs

The Outcome of the Treatments of Chest Trauma Patients

Ninety-nine patients with chest trauma were clinically evaluated in terms of their prognoses. In accordance with advances in thoracic surgery, the survival rates were remarkably improved. However, six deaths were encountered in this series. The causes of deaths were attributable to associated injuries extend to two or three regions including the head and the abdomen so that precise detection and proper treatments should be made as quickly as possible. In conclusion, the prognoses of serious chest trauma patients are influenced by the presence and the degree of concomitant injuries as well as proper urgent managements

Esophageal Carcinomas with Synchronous and Metachronous Primary Malignant Carcinomas in Other Organs

Seventeen patients with 10 synchronous and 7 metachronous double cancers with carcinomas of the esophagus were surgically treated in the First Department of Surgery, Nagasaki University School of Medicine. All patients were men with an average of age 68.5. The incidence of double cancers with carcinoma of the esophagus accounted for 12.7% in a total of 134 of this series. The three triple cancers were included. Of the three, one was synchronous triple cancers in the esophagus, the stomach and the colon. The outcome was not necessarily satisfactory. Two had recurrence 3 and 5 months after surgery, but one is still alive for 33 months, free from carcinoma

Significance of Needle Aspiration Biopsy for Breast Cancer

The results of aspiration biopsy cytology were clinically evaluated on the basis of clinical experience with 608 patients with breast cancer at the First Department of Surgery, Nagasaki University School of Medicine. Aspiration biopsy is of clinical value in making a diagnosis of small-sized tumors. There was no detrimental outcome to promote tumor-cell spread locally as well as to give rise to distant metastasis into the other organ. One should be aware of a no cell finding in relation to scirrhous carcinoma and intraductal papillomatosis. Emphasis is placed on recommendation of open biopsy without repeated aspiration maneuver

Patterning of the Dorsal-Ventral Axis in Echinoderms: Insights into the Evolution of the BMP-Chordin Signaling Network

Formation of the dorsal-ventral axis of the sea urchin embryo relies on cell interactions initiated by the TGF beta Nodal. Intriguingly, although nodal expression is restricted to the ventral side of the embryo, Nodal function is required for specification of both the ventral and the dorsal territories and is able to restore both ventral and dorsal regions in nodal morpholino injected embryos. The molecular basis for the long-range organizing activity of Nodal is not understood. In this paper, we provide evidence that the long-range organizing activity of Nodal is assured by a relay molecule synthesized in the ventral ectoderm, then translocated to the opposite side of the embryo. We identified this relay molecule as BMP2/4 based on the following arguments. First, blocking BMP2/4 function eliminated the long-range organizing activity of an activated Nodal receptor in an axis rescue assay. Second, we demonstrate that BMP2/4 and the corresponding type I receptor Alk3/6 functions are both essential for specification of the dorsal region of the embryo. Third, using anti-phospho-Smad1/5/8 immunostaining, we show that, despite its ventral transcription, the BMP2/4 ligand triggers receptor mediated signaling exclusively on the dorsal side of the embryo, one of the most extreme cases of BMP translocation described so far. We further report that the pattern of pSmad1/5/8 is graded along the dorsal-ventral axis and that two BMP2/4 target genes are expressed in nested patterns centered on the region with highest levels of pSmad1/5/8, strongly suggesting that BMP2/4 is acting as a morphogen. We also describe the very unusual ventral co-expression of chordin and bmp2/4 downstream of Nodal and demonstrate that Chordin is largely responsible for the spatial restriction of BMP2/4 signaling to the dorsal side. Thus, unlike in most organisms, in the sea urchin, a single ventral signaling centre is responsible for induction of ventral and dorsal cell fates. Finally, we show that Chordin may not be required for long-range diffusion of BMP2/4, describe a striking dorsal-ventral asymmetry in the expression of Glypican 5, a heparin sulphated proteoglycan that regulates BMP mobility, and show that this asymmetry depends on BMP2/4 signaling. Our study provides new insights into the mechanisms by which positional information is established along the dorsal-ventral axis of the sea urchin embryo, and more generally on how a BMP morphogen gradient is established in a multicellular embryo. From an evolutionary point of view, it highlights that although the genes used for dorsal-ventral patterning are highly conserved in bilateria, there are considerable variations, even among deuterostomes, in the manner these genes are used to shape a BMP morphogen gradient