Endometrioid adenocarcinoma arising from endometriosis of the mesenterium of the sigmoid colon

This report presents a case of endometrioid adenocarcinoma arising from endometriosis of the mesenterium of the sigmoid colon following total abdominal hysterectomy and bilateral salpingo-oophorectomy for leiomyoma of the uterus and infiltrating pelvic endometriosis, and hormone replacement therapy. A 62-year-old woman presented with an abdominal tumor. Based on the diagnosis of mesocolonic tumor, sigmoidectomy with lymph node resection was performed. The tumor cells were immunopositive for cytokeratin 7, but negative for cytokeratin 20, and the tumor was histologically diagnosed as endometrioid adenocarcinoma of the mesocolon. Hyperestrogenism has been implicated as a risk factor for the development of cancer from endometriosis. The patient had been receiving high-dose unopposed estrogens for 14 years after a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Physicians should recognize that endometriosis-associated neoplasms are able to cause symptoms or signs such as abdominal and/or pelvic pain, pelvic mass, and vaginal bleeding, especially if the patient has been treated with hormone replacement therapy. It is important to recognize the possibility of tumors arising from endometriosis when evaluating intestinal or mesenteric neoplasms in women, even in the patient who has previously undergone total abdominal hysterectomy and bilateral salpingo-oophorectomy, particularly if the patient has a history of endometriosis and has received hormone replacement therapy.     

Targeted ablation of Fgf23 demonstrates an essential physiological role of FGF23 in phosphate and vitamin D metabolism

Inorganic phosphate is essential for ECM mineralization and also as a constituent of important molecules in cellular metabolism. Investigations of several hypophosphatemic diseases indicated that a hormone-like molecule probably regulates serum phosphate concentration. FGF23 has recently been recognized as playing important pathophysiological roles in several hypophosphatemic diseases. We present here the evidence that FGF23 is a physiological regulator of serum phosphate and 1,25-dihydroxyvitamin D (1,25[OH]2D) by generating FGF23-null mice. Disruption of the Fgf23 gene did not result in embryonic lethality, although homozygous mice showed severe growth retardation with abnormal bone phenotype and markedly short life span. The Fgf23(-/-) mice displayed significantly high serum phosphate with increased renal phosphate reabsorption. They also showed an elevation in serum 1,25(OH)2D that was due to the enhanced expression of renal 25-hydroxyvitamin D-1alpha-hydroxylase (1alpha-OHase) from 10 days of age. These phenotypes could not be explained by currently known regulators of mineral homeostasis, indicating that FGF23 is essential for normal phosphate and vitamin D metabolism.     

Experimentelle Untersuchungen über die Genese atypischer Epithelwucherungen

Ohne ZusammenfassungHierzu 5 Textfiguren.     

Ketamine interacts with the noradrenaline transporter at a site partly overlapping the desipramine binding site

Effects of the intravenous anaesthetic ketamine on the desipramine-sensitive noradrenaline transporter (NAT) were examined in cultured bovine adrenal medullary cells and in transfected Xenopus laevis oocytes expressing the bovine NAT (bNAT). Incubation (1–3 h) of adrenal medullary cells with ketamine (10–300 μM) caused an increase in appearance of catecholamines in culture medium. Ketamine (10–1000 μM) inhibited desipramine-sensitive uptake of [³H] _{noradrenaline} (NA) (IC₅₀=97 μM). Saturation analysis showed that ketamine reduced V _max of [³H]NA uptake without changing K _m, indicating a non-competitive inhibition. Other inhibitors of NAT, namely cocaine and desipramine, showed a competitive inhibition of [³H]NA uptake while a derivative of ketamine, phencyclidine, showed a mixed type of inhibition. Ketamine (10–1000 μM) also inhibited the specific binding of [³H]desipramine to plasma membranes isolated from bovine adrenal medulla. Scatchard analysis of [³H]desipramine binding revealed that ketamine increased K _d without altering B _max, indicating a competitive inhibition. In transfected Xenopus oocytes expressing the bNAT, ketamine attenuated [³H]NA uptake with a kinetic characteristic similar to that of cultured adrenal medullary cells. These findings are compatible with the idea that ketamine non-competitively inhibits the transport of NA by interacting with a site which partly overlaps the desipramine binding site on the NAT. Received: 18 December 1997 / Accepted: 17 June 1998     

Anti‐FGF23 Neutralizing Antibodies Show the Physiological Role and Structural Features of FGF23

Fibroblast growth factor (FGF)23 is proposed to play a physiological role in the regulation of phosphate and vitamin D metabolism; deranged circulatory levels of FGF23 cause several diseases with abnormal mineral metabolism. This paper presents a novel approach to analyze the mechanism of action of FGF23 using anti‐FGF23 monoclonal antibodies that can neutralize FGF23 activities both in vitro and in vivo. We developed two antibodies (FN1 and FC1) that recognize the N‐ and C‐terminal regions of FGF23, respectively. Both FN1 and FC1 inhibited FGF23 activity in a cell‐based Klotho‐dependent reporter assay. Their administration caused marked increases in serum phosphate and 1,25D levels in normal mice. These changes were accompanied by altered expression in the kidney of type IIa sodium‐phosphate cotransporter, 25‐hydroxyvitamin‐D‐1α‐hydroxylase, and 24‐hydroxylase. Thus, this study using neutralizing antibodies confirms that FGF23 is a physiological regulator of phosphate and vitamin D metabolism. We addressed the mechanism of action for these neutralizing antibodies. Structural analysis of the FGF23/FN1‐Fab complex showed that FN1 masked putative FGF receptor‐binding sites in the N‐terminal domain of FGF23, whereas biochemical analyses showed that FC1 interfered with the association between FGF23 and Klotho by binding to the C‐terminal domain of FGF23. Taken together, our results suggest that the N‐ and C‐terminal domains of FGF23 are responsible for association with cognate FGF receptors and Klotho, respectively, and that these interactions are indispensable for FGF23 activity.     

The effect of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) on pulmonary ischemia-reperfusion injury in a canine model

This study evaluates the effectiveness of direct hemoperfusion with a polymyxin B-immobilized fiber column (DHP-PMX therapy) on warm ischemia-reperfusion injury of the lung using a canine mode. MATERIALS AND METHODS: Ten adult mongrel dogs weighing 13-16 kg were used. After a left thoracotomy, the left pulmonary artery and vein were clamped. The left main bronchus was also clamped and then divided, and complete ischemia of the left lung was maintained for 3 h. The left main bronchus was re-anastomosed before reperfusion of the left lung. The right pulmonary artery was ligated immediately after reperfusion of the left lung. The dogs were divided into two groups: the DHP-PMX group (n = 5, DHP-PMX was performed for 120 min, from 30 min before reperfusion to 90 min after reperfusion) and the control group (n = 5). The body temperature of the animals was maintained at 36 degrees C-37 degrees C during the experiment. The PaO2/FiO2 (P/F ratio), AaDO2, and lt-pulmonary vascular resistance (PVR) were measured at 30, 60, 120, 180, and 240 min after reperfusion in both groups, and the two groups were compared. The water content of the lung tissues and histopathology was also analyzed. RESULTS: The P/F ratio decreased remarkably after reperfusion in the control group, and was significantly (p < .05) lower than that in the PMX-DHF group until 240 min after reperfusion. The AaDO2 was significantly (p < .05) lower in the DHP-PMX group than in the control group at 30, 60, and 120 min after reperfusion. The lt-PVR level differed significantly (p < .05) between the two groups until 240 min after reperfusion. The water content in the control group was significantly (p < .05) higher than that in the DHP-PMX group at 240 min after reperfusion. Lung tissues at 120 and 240 min after reperfusion were better preserved pathologically in the DHP-PMX group. CONCLUSION: DHP-PMX therapy reduced warm ischemia-reperfusion injury in the lung using a canine model.     

Transplacental induction of myeloschisis associated with hindbrain crowding and other malformations in the central nervous system in Long-Evans rats

Nine groups of 66 pregnant rats, grouped by gestation days 11 to 19, were subjected to a single, intragastric administration of ethylenethiourea (ETU). Cesarean section was performed on gestation day 20. No dam died following the ETU treatment, although a mortality as high as 21.2% was noted among the fetuses in this group; the remaining live fetuses were found to suffer from a high incidence of myeloschisis associated with hindbrain crowding. Exencephaly and abnormally enlarged head with occipital bossing due to the herniation of the mesencephalic tectum, with and without dilation of the mesencephalic and 4th ventricles, were induced among the fetuses of the dams given ETU at gestation days 12 and 13. Various degrees of hydranencephaly and dysplastic hydrocephalus were found among the fetuses of dams treated by ETU from gestation days 14 to 18. From the histological features of these malformations of the central nervous system (CNS), a possible mechanism in the induction of myeloschisis with hindbrain crowding induced by ETU is discussed, and compared with the previously reported similar malformations induced by trypan blue.Presented at the 12th Scientific Meeting of the International Society for Paediatric Neurosurgery, Cairo, 1984     

Advantage of using CBA/N strain mice in a non-radioisotopic modification of the local lymph node assay

The murine local lymph node assay (LLNA) is currently recognized as a stand-alone test method for determining the skin sensitizing potential of chemicals. It has been incorporated into the official test guidelines published by some authorities, including the OECD. To avoid the use of radioisotopes, efforts have been made recently to develop non-radioisotopic modifications of the LLNA. A non-radioisotopic modification of the LLNA was developed previously using 5-bromo-2'-deoxyuridine (BrdU) incorporation (non-RI LLNA). However, the non-RI LLNA was found to be somewhat less sensitive than the standard assay. This study reports the advantage of using mice of the CBA/N strain in the non-RI LLNA to improve the sensitivity of this method. The non-RI LLNA was performed using CBA/JN and CBA/N mice exposed to one of four confirmed skin sensitizers, 2,4-dinitrochlorobenzene (DNCB), eugenol (EG), isoeugenol (IEG) or alpha-hexylcinnamic aldehyde (HCA), and to one non-sensitizer, propylene glycol (PG). The EC3 values for DNCB, IEG, EG, HCA and PG were calculated to be 0.1%, 9.6%, 40.6%, 45.5% and >50% in CBA/JN mice and 0.08%, 1.9%, 10.7%, 20.3% and >50% in CBA/N mice, respectively. The EC3 values for DNCB, IEG, EG, HCA and PG in the standard LLNA using CBA/Ca mice and radioisotopes were reported elsewhere as being 0.08%, 1.3%, 13.0%, 8.0% and >50%, respectively. The EC3 values derived from the CBA/N mice in the non-RI LLNA were nearly equivalent to the EC3 values obtained using the standard radioisotopic LLNA with CBA/Ca mice. These data suggest that the use of CBA/N mice may provide a realistic opportunity to develop a version of the LLNA that does not have a requirement for the use of radioisotopes, but which nevertheless has sensitivity approaching, or comparable to, the standard method.