[Decision making support for chemotherapy outpatients and their families: role of the home care professional].

The intervention of palliative care from the early stages of cancer is advocated, however, current situation remains virtually unchanged. Since the Baptist Home Hospice Palliative Care Clinic opened, the percentage of patients who have been introduced to the clinic during chemotherapy and have received home-visit care is 16.1%. Of those, the percentage of patients who passed away more than two months since the start of home-visit care is 45.7%. We determine the direction in care by listening closely to our patients and their families, and putting advance care planning (ACP) into effect. One of our roles is to offer support in deciding to discontinue the treatment in the final stages of chemotherapy. It is recognized that a number of patients are undergoing ineffective chemotherapy, despite the strong side effects. Our clinic strives to help these patients spend time the way they want by providing home-visit care and home-visit nursing.

[Palliative care for patients with hematological malignancies in the Japan Baptist Medical Foundation].

The Japan Baptist Medical Foundation has established a "hospice triangle" system consisting of the hospice ward, general ward, and home hospice. Palliative care is provided for patients with various types of cancer, including hematological malignancies, in the place where they desire to receive care. From December 2010 to December 2013, 37 patients with hematological malignancies received palliative care and died at our foundation. Eleven (30%) patients died in the hospice ward, 24 (65%) in the general ward, and 2 (5%) at home. The median interval between the final dose of chemotherapy and death was 12 (1- 88) days. Twenty (54%) patients received transfusions during the last 2 weeks prior to death. Quick response to patient situations and early introduction of palliative care are essential to support end-of-life decision-making processes, because the clinical course of hematological malignancies generally differs from that of other cancers.

Mitochondria-targeted superoxide dismutase (SOD2) regulates radiation resistance and radiation stress response in HeLa cells.

Reactive oxygen species (ROS) act as a mediator of ionizing radiation-induced cellular damage. Previous studies have indicated that MnSOD (SOD2) plays a critical role in protection against ionizing radiation in mammalian cells. In this study, we constructed two types of stable HeLa cell lines overexpressing SOD2, HeLa S3/SOD2 and T-REx HeLa/SOD2, to elucidate the mechanisms underlying the protection against radiation by SOD2. SOD2 overexpression in mitochondria enhanced the survival of HeLa S3 and T-REx HeLa cells following γ-irradiation. The levels of γH2AX significantly decreased in HeLa S3/SOD2 and T-REx HeLa/SOD2 cells compared with those in the control cells. MitoSox(TM) Red assays showed that both lines of SOD2-expressing cells showed suppression of the superoxide generation in mitochondria. Furthermore, flow cytometry with a fluorescent probe (2',7'-dichlorofluorescein) revealed that the cellular levels of ROS increased in HeLa S3 cells during post-irradiation incubation, but the increase was markedly attenuated in HeLa S3/SOD2 cells. DNA microarray analysis revealed that, of 47,000 probe sets analyzed, 117 and 166 probes showed more than 2-fold changes after 5.5 Gy of γ-irradiation in control and HeLa S3/SOD2 cells, respectively. Pathway analysis revealed different expression profiles in irradiated control cells and irradiated SOD2-overexpressing cells. These results indicate that SOD2 protects HeLa cells against cellular effects of γ-rays through suppressing oxidative stress in irradiated cells caused by ROS generated in the mitochondria and through regulating the expression of genes which play a critical role in protection against ionizing radiation.

Azoospermia in patients heterozygous for a mutation in SYCP3.

BACKGROUND: Many cases of male infertility are diagnosed as idiopathic, reflecting poor understanding of the molecular defects underlying the abnormality. As more gene mutations causing male infertility in mice become known, there are improving prospects that knowledge about the genetic aetiology of human male infertility can be expanded. Sycp3 encodes a component of the synaptonemal complex. A null mutation of Sycp3 in mice causes azoospermia with meiotic arrest. We tested the hypothesis that mutation of the human testis-specific SYCP3 is associated with human non-obstructive azoospermia. METHODS: Human SYCP3 was isolated on the basis of homology between mouse Sycp3 cDNA and human genome sequences at the aminoacid level. Tissue-specific expression of SYCP3 was analysed by PCR of human cDNA. Samples of DNA from 19 azoospermic patients with maturation arrest and 75 normal fertile control men were screened for mutations in the SYCP3 gene by sequence analysis of the gene. The functional significance of the mutations found was analysed by a protein interaction study of the wild-type and truncated SYCP3 proteins. FINDINGS: We identified in two patients a 1 bp deletion (643delA) that results in a premature stop codon and truncation of the C-terminal, coiled-coil-forming region of the SYCP3 protein. The mutant protein showed greatly reduced interaction with the wild-type protein in vitro and interfered with SYCP3 fibre formation in cultured cells. INTERPRETATION: We suggest that SYCP3 has an essential meiotic function in human spermatogenesis that is compromised by the mutant protein via dominant negative interference.

Molecular cloning and expression analysis of the mouse Spot-2 gene in pituitary development.

Mouse Spot-1 is a DNA-binding protein with a domain (His-Thr) encoded by p(CA)n repeats. Spot-1 interacts with the nuclear localization signal (NLS) I of p53 through its His-Thr domain. In this study we describe the cloning and expression patterns of a novel gene encoding a protein containing a His-Thr domain, Spot-2. Spot-2 is exclusively expressed in the pituitary from stage E13.5 to E15.5. Mouse Lhx3 plays a critical role during early organogenesis in the pituitary. The Spot-2 gene appears to be a downstream gene of Lhx3. It is suggested that Spot-2 plays important roles in pituitary development.

Isolation and expression analysis of the testis-specific gene, STRA8, stimulated by retinoic acid gene 8.

Retinoids are known to be required for vertebrate reproduction, and in the male, for the maintenance of normal testicular structure and function. Previously several novel retinoic acid responsive genes, collectively designated as the Stra genes, had been isolated in the mouse. The Stra8 gene encodes a cytoplasmic protein and is expressed specific to the developing male gonad during mouse embryogenesis. In adult mouse, its expression is restricted to the premeiotic germ cells. Thus it has been suggested that the mouse Stra8 protein may play a role in the premeiotic phase of spermatogenesis. Recently a lot of genes that are expressed only in male germ cells have been isolated in the mouse. The mouse Stra8, Rnh2, Piwil2, Tex17, and Tuba7 were identified as testis-specific expressed genes. In addition, the Figla was known to be a testis- and ovary-specific gene. Recently we had reported the isolation of the human RNH2 cDNA and its expression, which is limited to the human testis. In the present study, we have isolated full-length cDNA of S TRA8 and partial cDNAs of PIWIL2, FIGLA, TEX17, and TUBA7, and analyzed their expression patterns in human tissues.

Molecular cloning and expression analysis of MPP alpha-2, a novel mouse transcript detected in a differential screen of pituitary libraries.

We identified a novel isoform transcript, MPP alpha-2, of the mouse Mg(2+)-dependent protein phosphatase (MPP) alpha gene. The amino acid sequence encoded by MPP alpha-2 differs from the previously known MPP alpha-1 sequence only at the carboxyl terminal region. Northern and in situ hybridization analysis revealed differential expression patterns of these two transcripts in the embryo and in the adult organism, suggesting an elaborate regulation of the MPP alpha gene.

Isolation and expression analysis of the human RNH2 gene encoding ribonuclease inhibitor 2.

Ribonuclease inhibitor 1 (RI-1) is a cytoplasmic protein that inhibits a variety of pancreatic-type mammalian Rnases by forming a very tight, reversible 1:1 complex. Recently a novel gene encoding ribonuclease inhibitor 2, Rnh2 has been isolated in mouse. The expression pattern of the mouse Rnh2 is specific to testis, especially in the spermatogonia. Then it has been suggested that the mouse Rnh2 gene may play critical roles in mouse spermatogenesis. In this study, we isolated the human RNH2 cDNA and analyzed its expression pattern. The human RNH2 is also expressed limited to testis, and then it is suggested that the human Rnh2 gene may also play critical roles in human spermatogenesis.

The human ASCL2 gene escaping genomic imprinting and its expression pattern.

The mouse achaete-scute homolog-2 gene (Ascl2 or Mash2) encodes a transcription factor playing a role in the development of the trophoblast. The Ascl2 is an imprinted gene with maternal expression and assigned to an imprinting gene cluster region (ICR) at a distal region of mouse chromosome 7. We previously isolated a phage clone carrying the human homolog, ASCL2, and mapped it to human chromosome 11p15.5, a human ICR. In the present study, we demonstrate the expression patterns of the human ASCL2 in the fetus at a stage between first and second trimesters and in the placental tissues. In addition, it has been shown that the human ASCL2 gene escapes genomic imprinting.