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A 54-year-old man was transferred to our ICU because of systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). He died after 38 days of intensive care. During treatment, his serum calcium (Ca) levels continued to increase and reached 3.95 mmol/L, while the ionized Ca levels reached 2.30 mmol/L before his death. He presented with severe kidney injury, pancreatitis, and hemorrhagic gastric erosion that worsened his prognosis; these were possibly associated with the hypercalcemia. His circulating 1alpha,25-dihydroxyvitamin D [1,25(OH)(2)D] level was elevated (75.7 to 204 pg/mL), whereas the levels of 25-hydroxyvitamin D, parathyroid hormone, and parathyroid hormone-related peptide were not. Liver histology revealed immunoreactivity for 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1) in some of the hepatocytes, in which the localization pattern was similar to that of lysozyme-positive hepatocytes. Our ICU has previously encountered 22 similar MODS patients who presented with hypercalcemia over the last 8 years. SIRS with severe kidney and liver injuries are common clinical findings in hypercalcemic patients with MODS. Of the 23 hypercalcemic MODS patients, including the present patient, 17 had circulating 1,25(OH)(2)D levels exceeding 70 pg/mL despite severe kidney injury. Extrarenal activation of CYP27B1 seems to play a role in the development of hypercalcemia in this disease condition. Clinicians need to be aware that severe hypercalcemia may occur in MODS patients., ((c) 2010 American Society for Bone and Mineral Research.)

Objective: Predicted postoperative forced expiratory volume in 1s (ppoFEV1) is estimated in lung cancer patients before pulmonary resection, as well as the clinical stage. This study aims to evaluate ppoFEV1 and ppo-vital capacity (ppoVC) on postoperative day 7 (POD7) and to compare the results following video-assisted thoracic surgery (VATS) and open thoracotomy procedures., Methods: Of the 155 patients who underwent pulmonary resection, 70 had VATS; 30 had muscle-sparing thoracotomy (anterior limiting thoracotomy (AL)); and 55 had postero-lateral thoracotomy (PL). VC and FEV1 were measured on POD7 and compared with the VC and FEV1 before surgery using analysis of covariance (ANCOVA). The ratio of the actual- and the ppoVC and FEV1 was evaluated to identify factors associated with variations in postoperative residual VC/FEV1., Results: There were significant differences by analysis of covariance (ANCOVA) in the VC/FEV1 among the three surgical approaches. In the VATS group, the VC ratio and the FEV1 ratio were 96.5% and 94.7%, respectively; they were significantly higher in the VATS group than in the thoracotomy group (AL: 90.4% and 90.1%, respectively; PL: 87.4% and 87.6%, respectively). Non-chronic obstructive pulmonary disease (COPD) and upper lobectomy were also associated with a low VC ratio and FEV1 ratio., Conclusion: Predicted postoperative pulmonary function might be overestimated in COPD patients or in those undergoing VATS or lower lobectomy., (Copyright 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

The fetal brain is thought to have a role in the onset and progression of labor. Evidence also exists for fetal oxytocin release just before and during parturition. The present study examined whether activation of the fetal brain could induce uterine myometrial contractions through oxytocin receptors in the dam. Under urethane anesthesia, electrical stimulation of the hypothalamus of fetal rats that were still connected with the dams by an intact umbilical cord induced uterine contractions in term pregnant rats. Intraperitoneal injections of synthetic oxytocin in fetuses induced uterine contractions in the dams similar to those induced by electrical stimulation of the fetal hypothalamus. Maternal intravenous injections of an oxytocin antagonist immediately attenuated uterine contractions induced by fetal oxytocin injections and electrical stimulation of the fetal hypothalamus. These findings suggest the possibility that oxytocin released from the fetal hypothalamus is involved in parturition.

NCp8 of HIV-2 contains two CCHC-type zinc fingers connected by a linker, and is involved in many critical steps of the virus life cycle. It was previously shown that the first zinc finger flanked by the linker is the minimal active domain for specific binding to viral RNA. In our previous study, we determined the three-dimensional structure of NCp8-f1, including the minimal active domain, and found that a hydrogen bond between Asn(11) N(delta)H and Arg(27) O stabilized the conformation of the linker in the vicinity of the zinc finger [Kodera et al. (1998) Biochemistry 37, 17704-17713]. In this study, RNA binding activities of NCp8-f1 and three types of its mutant peptides were analysed by native PAGE assay. The activity and three-dimensional structure of NCp8-f1/N11A, in which alanine is substituted for Asn(11) thereby affecting the conformation of the linker, was analyzed and compared with those of NCp8-f1. We demonstrated that the existence of Arg(4) and/or Lys(5) and Arg(26) and/or Arg(27) were necessary for binding RNA. Furthermore, the linker's flexible orientation, which is controlled by the hydrogen bond between Asn(11) N(delta)H and Arg(27) O, appears to be a structural basis for NCp8 existing as a multi-functional protein.

To screen a wide variety of chemicals for endocrine disrupters, and to develop an effective microbial degradation system for them, a good system is needed for the rapid and accurate evaluation of the endocrine-disrupting activities of suspected chemicals and their degradation products. We constructed two-hybrid systems that co-express the Gal4p DNA binding domain/ligand-binding domain of human estrogen receptor (hER) alpha or beta and the Gal4p transactivation domain/nuclear receptor-binding domain of co-activator SRC1, TIF2, or AIB1 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of Gal4p-binding sites. We found that the combination of the hERbeta ligand-binding domain and SRC1 nuclear receptor-binding domain was most effective for the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by known xenoestrogens and phytoestrogens was found to correlate well with their estrogenic activities as measured by the previous system with rat ERalpha. This system detects estrogenic activity in some chemicals that have not been suspected of being positive. We also applied this assay system to test the microbial degradation products of gamma-hexachlorocyclohexane (gamma-HCH) by Sphingomonas paucimobilis. Among the gamma-HCH metabolites, 2,5-dichlorohydroquinone and chlorohydroquinone had estrogenic activities similar to the original chemical, while hydroquinone, a later stage metabolite, showed no activity, suggesting the necessity of evaluating intermediate metabolites in microbial degradation systems.

The presence of bone-specific estrogen agonists and discovery of the osteoblast-specific transcription factor (TF), Cbfa1, together with the discovery of synergism between a TF Pit-1 and estrogen receptor alpha (ERalpha) on rat prolactin gene, led to investigation of Cbfa1 in the modulation of osteoblast-specific actions of estrogen. Reverse transcribed-polymerase chain reaction demonstrated expression of Cbfa1 in the osteoblastic cell lines, MG63, ROS17/2.8, and MC3T3E1, but not in nonosteoblastic cell lines, MCF7, C3H10T1/2, and HeLa. An ER expression vector and a series of luciferase (Luc) reporter plasmids harboring the Cbfa1 binding site OSE2 (the osteoblast-specific cis element in the osteocalcin promoter) and palindromic estrogen response elements (EREs) were cotransfected into both osteoblastic and nonosteoblastic cells. OSE2 worked as a cis- acting element in osteoblastic cells but not nonosteoblastic cells, whereas EREs were cis- acting in all cell lines. Synergistic transactivation was observed in osteoblastic cells only when both ERE and OSE2 were placed in juxtaposition to the promoter. Forced expression of Cbfa1 in C3H10T1/2 cells also induced synergism. Tamoxifen, a partial agonist/antagonist of estrogen, acted as an osteoblast-specific agonist in cells transfected with a promoter containing ERE and acted synergistically with a promoter containing the ERE-OSE2 enhancer combination. These results support the idea that bone-specific TFs modulate the actions of estrogen in a tissue-specific manner.

Several aspects of total genomic DNA transcription in a HeLa cell extract were described. (1) By using in vitro transcripts from total genomic DNA as probes, we elucidated several structures of short interspersed elements which are transcribed by RNA polymerase III (designated as Pol III/SINEs. (2) To know whether the repetitive sequence we cloned and sequenced comprises a major or minor family, we developed in vitro run-off transcription assay of total genomic DNA. (3) Unlike in vitro transcription of total genomic DNA from vertebrates, major in vitro transcripts from macronuclear total DNA of Tetrahymena were found to be tRNA themselves.