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1.
Nurs Rep ; 14(1): 25-41, 2023 Dec 23.
Article in English | MEDLINE | ID: mdl-38251181

ABSTRACT

Japan has accepted nurses from Indonesia, the Philippines, and Vietnam under the Economic Partnership Agreement, but nearly half of them have already left the workforce. This study aimed to clarify the factors related to the job continuance of nurses who migrated to Japan under the Economic Partnership Agreement. Our goal was to explore factors specific to migrant nurses and to contribute to the development of support measures for them. This research was a cross-sectional study in which a web-based questionnaire and interview were conducted at a single point in time. Migrant nurses (n = 40) participated in the web-based questionnaire survey. Of those, nine nurses were also interviewed. Spearman's rank correlation coefficient was used to establish correlations, and qualitative descriptive analysis was used to analyse interviews. The questionnaire survey results revealed the content of work, human relationships in the workplace, the number of night shifts, and satisfaction with the balance between work and private life were significantly and negatively correlated with the Intention to Quit scale total score. All correlation coefficients were less than 0.5, indicating weak correlations. Three categories emerged from the interviews as positive factors related to job continuance: "generous support from the workplace", "beneficial nursing experience in Japan", and "determination to live in Japan". A good working environment, generous support from the supervisor and colleagues, high values of nursing in Japan, and desire to migrate to Japan were the factors that had a positive effect on migrant nurses' job continuance in Japan. Understanding the characteristics of migrant nurses and providing generous support will enable them to continue working in Japan. This study was not registered.

2.
BMC Pediatr ; 22(1): 414, 2022 07 13.
Article in English | MEDLINE | ID: mdl-35831839

ABSTRACT

BACKGROUND: Despite the potential benefits of effective communication, telling a child that they have a life-threatening condition is one of the most daunting challenges. This study aimed to explore the information needs of children with leukemia from the perspectives of children and their parents at the time of diagnosis. METHODS: We conducted an exploratory qualitative study using semi-structured individual interviews with children diagnosed with leukemia between seven and 13 years old (n = 7) and their parents (n = 9). Children and parents' interview data were analyzed using thematic analysis. RESULTS: We identified three themes for the information needs of children with leukemia, 1) beginning to cope, 2) avoiding disclosure - protecting child, and 3) informational support. The children and their parents needed to receive understandable information at the best time to cope with cancer. However, the children and parents expressed different views about children's information needs. The children needed clear information about the disease, treatment, hospitalization, and the benefits of hospitalization from the time of diagnosis. In contrast, the parents felt they should not tell their children about the disease if they were in shock by their child's cancer diagnosis. Moreover, the parents believed that information that would be incomprehensible to the child and distress should be avoided to protect their children. CONCLUSIONS: While the information needs of children with leukemia are varied, children and their parents need the information to cope with cancer. However, if the parents believe that the information would be distressful, they might manage communication with their children. Healthcare professionals should explore the motivations behind parents' attitudes against communication with children and confront conflict. Healthcare professionals also should communicate with the children and their parents to understand their information needs and respect children's views.


Subject(s)
Leukemia , Parents , Adolescent , Child , Communication , Humans , Leukemia/therapy , Professional-Family Relations , Qualitative Research
3.
J Clin Med ; 11(12)2022 Jun 13.
Article in English | MEDLINE | ID: mdl-35743451

ABSTRACT

OBJECTIVES: we investigated the prevalence and associated factors of depression and complicated grief (CG) among bereaved family members of malignant pleural mesothelioma (MPM) patients in Japan. METHODS: Bereaved family members of MPM patients (n = 72) were surveyed. The Japanese version of the Patient Health Questionnaire-9 (PHQ-9) and the Japanese version of the Brief Grief Questionnaire (BGQ) were used to assess depression and complicated grief (CG), respectively. Socio-economic factors, anger toward asbestos, care satisfaction, achievement of good death, and quality of end-of-life care were assessed in relation to depression and CG. RESULTS: In the family members of MPM patients, the frequencies of depression and CG were 19.4% and 15.3%, respectively. The bereaved family members who were not compensated by the asbestos-related health-damage relief system (p = 0.018) and who felt the financial impacts of the patient's MPM on the family (p = 0.006) had a higher likelihood of depression. The bereaved family members who were not satisfied with the care given when the patient became critical (p = 0.034), who were not compensated by the asbestos-related health-damage relief system (p = 0.020), who felt the financial impact of the patient's MPM on the family (p = 0.016), and whose deceased relative underwent surgery (p = 0.030) had a higher likelihood of CG. CONCLUSIONS: For bereaved family members of MPM patients, routine screening for depression and CG and the provision of grief care are suggested. In addition, for family members of MPM patients, financial support, including the promotion of the asbestos-related health-damage relief system, and improved care for patients who undergo surgery and when patients become critical, are recommended.

4.
J Clin Med ; 11(9)2022 May 01.
Article in English | MEDLINE | ID: mdl-35566667

ABSTRACT

OBJECTIVE: This study investigated whether malignant pleural mesothelioma (MPM) patients achieved good deaths and good quality of end-of-life care compared with other cancer patients from the perspective of bereaved family members in Japan. METHODS: This cross-sectional study was part of a larger study on the achievement of good deaths of MPM patients and the bereavement of their family members. Bereaved family members of MPM patients in Japan (n = 72) were surveyed. The Good Death Inventory (GDI) was used to assess the achievement of good death. The short version of the Care Evaluation Scale (CES) version 2 was used to assess the quality of end-of-life care. The GDI and CES scores of MPM patients were compared with those of a Japanese cancer population from a previous study. RESULTS: MPM patients failed to achieve good deaths. Only 12.5% of the MPM patients were free from physical pain. The GDI scores of most of the MPM patients were significantly lower than those of the Japanese cancer population. The CES scores indicated a significantly poorer quality of end-of-life care for the MPM patients than the Japanese cancer population. The total GDI and CES scores were correlated (r = 0.55). CONCLUSIONS: The quality of end-of-life care for MPM patients remains poor. Moreover, MPM patients do not achieve good deaths from the perspective of their bereaved family members.

5.
J Med Internet Res ; 24(4): e34061, 2022 04 22.
Article in English | MEDLINE | ID: mdl-35451987

ABSTRACT

BACKGROUND: The poor coverage of essential maternal services, such as antenatal care (ANC) and skilled delivery care utilization, accounts for higher maternal and infant mortality in low- and middle-income countries (LMICs). Although mobile health (mHealth) interventions could potentially improve the service utilization in resource-limited settings, their effectiveness remains unclear. OBJECTIVE: This review aimed to summarize the effect of mHealth interventions on improving the uptake of ANC visits, skilled birth attendance at the time of delivery, and facility delivery among pregnant women in LMICs. METHODS: We conducted a comprehensive search on 9 electronic databases and other resources from inception to October 2020. We included individual randomized controlled trials and cluster randomized controlled trials that assessed the effectiveness of mHealth interventions for improving perinatal health care utilization among healthy pregnant women in LMICs. We performed a random-effects meta-analysis and estimated the pooled effect size by using risk ratios (RRs) with 95% CIs. In addition, 2 reviewers independently assessed the risk of bias of the included studies by using the Cochrane risk of bias tool and the certainty of the evidence by using the Grading of Recommendation, Assessment, Development and Evaluation approach. RESULTS: A total of 9 studies (10 articles) that randomized 10,348 pregnant women (n=6254, 60.44% in the intervention group; n=4094, 39.56% in the control group) were included in this synthesis. The pooled estimates showed a positive effect of mHealth interventions on improving 4 or more ANC visit utilizations among pregnant women in LMICs, irrespective of the direction of interventions (1-way communications: RR 2.14, 95% CI 1.76-2.60, I2=36%, 2 studies, moderate certainty; 2-way communications: RR 1.17, 95% CI 1.08-1.27, I2=59%, 3 studies, low certainty). Only 2-way mHealth interventions were effective in improving the use of skilled birth attendance during delivery (RR 1.23, 95% CI 1.14-1.33, I2=0%, 2 studies, moderate certainty), but the effects were unclear for 1-way mHealth interventions (RR 1.04, 95% CI 0.97-1.10, I2=73%, 3 studies, very low certainty) when compared with standard care. For facility delivery, the interventions were effective in settings where fewer pregnant women used facility delivery (RR 1.68, 95% CI 1.30-2.19, I2=36%, 2 studies, moderate certainty); however, the effects were unclear in settings where most pregnant women already used facility delivery (RR 1.01, 95% CI 0.97-1.04, I2=0%, 1 study, low certainty). CONCLUSIONS: mHealth interventions may contribute to improving ANC and skilled delivery care utilization among pregnant women in LMICs. However, more studies are required to improve their reproducibility and efficiency or strengthen the evidence of different forms of mHealth interventions because of the considerable heterogeneity observed in the meta-analyses. TRIAL REGISTRATION: PROSPERO CRD42020210813; https://tinyurl.com/2n7ny9a7.


Subject(s)
Prenatal Care , Telemedicine , Developing Countries , Female , Humans , Infant , Parturition , Pregnancy , Reproducibility of Results
6.
BMC Womens Health ; 20(1): 88, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32357884

ABSTRACT

BACKGROUND: Ensuring good health of immigrants is a serious issue across countries, including Japan. This study focused on the health of middle-aged female immigrants in Japan who experienced changes to their health as well as an increased risk of non-communicable diseases. Specifically, the study aimed to clarify the risks and perceptions of non-communicable diseases and health promotion behavior of middle-aged female immigrants in Japan. METHODS: This investigation used an exploratory design. The participants were a purposive sample of 35 middle-aged female immigrants (age ≥ 40 years) living in urban and rural areas of Japan. Data were generated using mixed methods. A quantitative approach provided data of their risks of non-communicable diseases. Focus group discussions provided insights to identify their health promotion perceptions. RESULTS: Blood pressure measurement revealed that 29% of the immigrants had hypertension, 29% had a body mass index of > 30, and 71% had an abdominal girth of > 80 cm. About 31% had a history of chronic disease and 34% had regular medication. There were 80% who received regular health check-up, 49% who received breast cancer screening, and 34% who received cervical cancer screening. The focus group discussions indicated that the middle-aged female immigrants recognized the threat of non-communicable diseases. However, they lacked knowledge about the prevention of non-communicable diseases, and they felt that non-communicable diseases were unavoidable. They also failed to understand the benefits of health promotion behavior. The study revealed that the monolingual Japanese health service prevented immigrant women from understanding their health check-up and cancer screening results, and how to utilize the health service system. CONCLUSIONS: Middle-aged female immigrants in Japan had potential risks of non-communicable diseases, and recognized their threat. These settled immigrant women received health check-ups and cancer screenings with the support of their family, and consequently attained the same level of adherence as that of Japanese women. However, lack of knowledge about health promotion and its benefits and the absence of a culturally sensitive health service system for immigrants in Japan constrained their health-promotion behavior. Sociocultural multilingual-tailored interventions including interpretation services by care providers with cultural sensitivities must be developed.


Subject(s)
Emigrants and Immigrants/psychology , Health Behavior/ethnology , Health Knowledge, Attitudes, Practice , Health Promotion , Noncommunicable Diseases/epidemiology , Women's Health/ethnology , Breast Neoplasms/prevention & control , Early Detection of Cancer , Female , Focus Groups , Humans , Japan/epidemiology , Middle Aged , Qualitative Research , Uterine Cervical Neoplasms/prevention & control
7.
BMC Cancer ; 19(1): 383, 2019 Apr 25.
Article in English | MEDLINE | ID: mdl-31023248

ABSTRACT

BACKGROUND: Malignant pleural mesothelioma (MPM) is a fatal and rare disease that is caused by the inhalation of asbestos. Treatment and care requests made by MPM patients to their physicians were collected and analyzed. METHODS: This cross-sectional survey was part of a larger study (N = 133) regarding the quality of life of MPM patients. Specific responses to two open-ended questions related to patients' requests regarding treatment and care were quantified, analyzed and divided into categories based on content. RESULTS: Responses (N = 217) from MPM patients (N = 73) were categorized into 24 subcategories and then abstracted into 6 categories. The majority of requests were related to patient-physician communication. Patients wanted clear and understandable explanations about MPM and wanted their physician to deliver treatment based on the patient's perspective by accepting and empathizing with their anxiety and pain. Patients expected physicians to be dedicated to their care and establish an improved medical support system for MPM patients. CONCLUSION: Patients with MPM had a variety of unmet needs from their physicians. Physicians who provide care to MPM patients should receive training in both communication skills and stress management. A multidisciplinary care system that includes respiratory and palliative care for MPM patients should be established.


Subject(s)
Asbestos/toxicity , Lung Neoplasms/epidemiology , Mesothelioma/epidemiology , Pleural Neoplasms/epidemiology , Adult , Aged , Environmental Exposure , Female , Humans , Japan/epidemiology , Lung Neoplasms/chemically induced , Lung Neoplasms/pathology , Male , Mesothelioma/chemically induced , Mesothelioma/pathology , Mesothelioma, Malignant , Middle Aged , Palliative Care , Physicians , Pleural Neoplasms/chemically induced , Pleural Neoplasms/pathology , Quality of Life
8.
BMC Cancer ; 18(1): 350, 2018 03 27.
Article in English | MEDLINE | ID: mdl-29587685

ABSTRACT

BACKGROUND: Previous studies have indicated that people with malignant pleural mesothelioma (MPM) have a poor quality of life (QOL); however, information about the QOL of people with MPM in Japan is anecdotal. The aims of this study were to investigate the QOL of survivors of MPM in Japan and to determine the factors that correlate with their QOL. METHODS: This was a cross sectional study. The included patients were those diagnosed with MPM in Japan. We created a self-administered questionnaire consisting of 64 questions. The questionnaires were sent to hospitals and patient advocacy groups, distributed to the patients, completed, and sent back to the researchers by postal mail. QOL was assessed with the European Organization for Research and Treatment of Cancer 16 questionnaire (QLQ) and the short version of the core domains of the Comprehensive Quality of Life Outcome questionnaire (CoQoLo). RESULTS: In total, 133 questionnaires were collected. The QLQ assessments demonstrated that the survivors of MPM most frequently complained of fatigue, pain, sleep disturbances, and dyspnea. The symptom scales were acceptable, but the functional scales were significantly poorer for the patients with poor performance statuses (PSs). The short CoQoLo assessment was very unfavorable for 'Being free from physical pain.' Being a long-term survivor and a survivor with a poor PS were significantly correlated with poor global health status. CONCLUSIONS: Survivors of MPM have impaired function, a variety of symptoms, and lower QOL. Survivors of MPM, even those in good physical condition, need broad support.


Subject(s)
Lung Neoplasms/epidemiology , Mesothelioma/epidemiology , Pleural Neoplasms/epidemiology , Quality of Life , Survivors , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Japan/epidemiology , Lung Neoplasms/therapy , Male , Mesothelioma/therapy , Mesothelioma, Malignant , Middle Aged , Palliative Care , Pleural Neoplasms/therapy , Surveys and Questionnaires
9.
Asian Pac J Cancer Prev ; 15(21): 9165-70, 2014.
Article in English | MEDLINE | ID: mdl-25422196

ABSTRACT

PURPOSE: This study evaluated the effect of an Educational PROGRAM on Palliative Care for MPM for Nurses in Japan. PROGRAM: The 5-h program consisted of lectures and care planning group work. MATERIALS AND METHODS: This study used a pretest-posttest design with a single cohort of nurses and included a Difficulties in Palliative Care for Patients with MPM (DPCMPM) Scale with 15 items. The pre- and posttest scores were compared using a t-test. RESULTS: We included 27 female nurses with a mean of 14.4 years of nursing experience. In 12 of 15 DPCMPM items, the posttest difficulty scores were lower than the pretest scores. Participants highly evaluated the program for validity, clarity, clinical usefulness, and the facilitators. The Palliative Care for MPM Handbook for Nurses was developed as an educational tool for clinical settings. CONCLUSIONS: The Educational PROGRAM on Palliative Care for MPM for Nurses was effective in reducing nursing difficulties.


Subject(s)
Education, Nursing , Lung Neoplasms/nursing , Mesothelioma/nursing , Palliative Care , Pleural Neoplasms/nursing , Program Evaluation , Empathy , Female , Follow-Up Studies , Humans , Mesothelioma, Malignant , Prognosis , Surveys and Questionnaires
10.
Nurse Educ Today ; 34(7): 1087-93, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24630905

ABSTRACT

PURPOSE: In Japan nursing care lags behind the growing population of patients with malignant pleural mesothelioma. This study evaluated an educational program for nurses about caring for patients with malignant pleural mesothelioma in Japan. METHOD: In this randomized controlled study relative to care for malignant pleural mesothelioma, Knowledge, Difficulties and Attitude were measured at baseline, at post-test and at follow-up one month later. The two-day program with a half-day follow-up program included lectures, group work, role-playing and group discussion. 188 participants were randomly assigned to the intervention group (program, n=96) and control group (n=92; self-study by a similar content handbook). At baseline the groups showed no statistical differences in Knowledge (p=0.921), Difficulty (p=0.458) and Attitude (p=0.922). Completing the study were 177 participants yielding 88 in the intervention group and 89 in the control group. Human rights and privacy of participants were protected. RESULTS: The Knowledge score was significantly higher in the intervention post-test (t=14.03, p=0.000) and follow-up test (t=8.98, p=0.000). Difficulty score was significantly lower in the intervention at post-test (t=-3.41, p=0.001) and follow-up test (t=-3.70, p=0.000). The Attitude score was significantly higher in the intervention post-test (t=7.11, p=0.000) and follow-up test (t=4.54, p=0.000). The two-way analysis of variance with repeated measures on time showed an interaction between time and group; the subsequent simple main effect test found significant differences (p=0.000-0.001) between groups for after-program and at follow-up and a significant difference (p=0.000) in time only within the intervention group. CONCLUSION: The educational program was effective in improving the nurses' knowledge and attitude toward malignant pleural mesothelioma care and decreasing the difficulty in MPM care, therefore this program has potential for nurses' in-service education throughout Japan.


Subject(s)
Education, Nursing/methods , Health Knowledge, Attitudes, Practice , Lung Neoplasms/nursing , Mesothelioma/nursing , Adult , Aged , Attitude of Health Personnel , Clinical Competence , Female , Humans , Japan , Male , Mesothelioma, Malignant , Middle Aged , Nurses , Program Evaluation
11.
Nihon Eiseigaku Zasshi ; 66(4): 717-23, 2011 Sep.
Article in Japanese | MEDLINE | ID: mdl-21996772

ABSTRACT

OBJECTIVE: In this research, we aimed to evaluate the support for asbestos health consultation in health centers. METHOD: In this exploratory descriptive study, a self-administered original questionnaire was developed and used. Among all 517 health centers, valid responses were returned from 323 (62.5%) consenting centers. RESULT: Consultations in the previous year ranged from 0-108 cases, with a facility median of 3.0 cases. Among staff members, 86.4% did not receive training and 35.4% had never used the manual. Workplaces that use asbestos within their jurisdiction were recognized by 39.2% of staff members, and 16.7% of these members always supported consultants psychologically. The staff members were not confident about asbestos health consultation: 71.2% for general questions, 76.2% for questions about asbestos-related diseases, and 76.4% for questions about risk of asbestos-related diseases; 51.4% were not confident about the Asbestos-Related Health Damage Relief System. Health center staff members who were significantly more confident were those who had more staff to work with; dealt with many consultations in the previous year; recognized the workplaces using asbestos within their jurisdiction; often used the manual and often psychologically supported consultants. According to the covariance structure analysis model, the 'use of support systems' consisting of 'the use of manual', 'training attendance' and 'recognition of workplaces that use asbestos' positively affected the frequency of psychological support (p<0.01) which promoted the confidence of staff members (p<0.01). The use of support systems also promoted the confidence of staff members directly (p<0.05). CONCLUSIONS: The support systems such as training, use of manual, and a list of workplaces using asbestos were effective in building the confidence of health center staff in relation to asbestos health consultation, although the use of these support systems was low.


Subject(s)
Asbestos , Community Health Centers , Referral and Consultation , Health Personnel/education , Health Personnel/psychology , Japan , Manuals as Topic
12.
Curr Biol ; 20(4): 322-7, 2010 Feb 23.
Article in English | MEDLINE | ID: mdl-20153198

ABSTRACT

Hemidesmosomes connect the extracellular matrix (ECM) to intermediate filaments through ECM receptors and plakins (plectin and BPAG1e). They affect tissue integrity, wound healing, and carcinoma invasion. Although biochemical and time-lapse studies indicate that alpha6beta4-integrin (ECM receptor) and plectin play a central role in modulating hemidesmosome disassembly, the mechanisms controlling hemidesmosome biogenesis in vivo remain poorly understood. The nematode C. elegans provides a powerful genetic model to address this issue. We performed a genome-wide RNA interference screen in C. elegans, searching for genes that decrease the viability of a weak VAB-10A/plakin mutant. We identified 14 genes that have human homologs with predicted roles in different cellular processes. We further characterized two genes encoding the chaperone CRT-1/calreticulin and the HECT domain E3 ubiquitin ligase EEL-1/HUWE1. CRT-1 controls by as little as 2-fold the abundance of UNC-52/perlecan, an essential hemidesmosome ECM ligand. Likewise, EEL-1 fine tunes by 2-fold the abundance of myotactin, the putative hemidesmosome ECM receptor. CRT-1 and EEL-1 activities, and by extension other genes identified in our screen, are essential during embryonic development to enable hemidesmosomes exposed to mechanical tension to mature into a tension-resistant form. Our findings should help understand how hemidesmosome dynamics are regulated in vertebrate systems.


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/embryology , Calreticulin/metabolism , Extracellular Matrix/metabolism , Hemidesmosomes/metabolism , Muscles/metabolism , Ubiquitin-Protein Ligases/metabolism , Animals , Blotting, Western , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Calreticulin/genetics , Fluorescent Antibody Technique , Genes, Essential/genetics , Heparan Sulfate Proteoglycans/metabolism , Models, Biological , Muscle Proteins/metabolism , Plakins/metabolism , RNA Interference , Reverse Transcriptase Polymerase Chain Reaction , Ubiquitin-Protein Ligases/genetics
13.
Development ; 134(13): 2469-79, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17537791

ABSTRACT

Embryonic morphogenesis involves the coordinate behaviour of multiple cells and requires the accurate balance of forces acting within different cells through the application of appropriate brakes and throttles. In C. elegans, embryonic elongation is driven by Rho-binding kinase (ROCK) and actomyosin contraction in the epidermis. We identify an evolutionary conserved, actin microfilament-associated RhoGAP (RGA-2) that behaves as a negative regulator of LET-502/ROCK. The small GTPase RHO-1 is the preferred target of RGA-2 in vitro, and acts between RGA-2 and LET-502 in vivo. Two observations show that RGA-2 acts in dorsal and ventral epidermal cells to moderate actomyosin tension during the first half of elongation. First, time-lapse microscopy shows that loss of RGA-2 induces localised circumferentially oriented pulling on junctional complexes in dorsal and ventral epidermal cells. Second, specific expression of RGA-2 in dorsal/ventral, but not lateral, cells rescues the embryonic lethality of rga-2 mutants. We propose that actomyosin-generated tension must be moderated in two out of the three sets of epidermal cells surrounding the C. elegans embryo to achieve morphogenesis.


Subject(s)
Actomyosin/metabolism , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/embryology , Caenorhabditis elegans/metabolism , Epidermis/embryology , Epidermis/metabolism , GTPase-Activating Proteins/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Morphogenesis , Protein Serine-Threonine Kinases/metabolism , Actins/metabolism , Animals , Animals, Genetically Modified , Caenorhabditis elegans Proteins/genetics , Embryo, Nonmammalian/embryology , Embryo, Nonmammalian/metabolism , GTPase-Activating Proteins/genetics , Gene Expression Regulation, Developmental , Intracellular Signaling Peptides and Proteins/genetics , Myosin-Light-Chain Phosphatase/genetics , Myosin-Light-Chain Phosphatase/metabolism , Protein Serine-Threonine Kinases/genetics , rho GTP-Binding Proteins/metabolism , rho-Associated Kinases
14.
Development ; 132(14): 3175-84, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15944183

ABSTRACT

We have analyzed the sma-5(n678) mutant in C. elegans to elucidate mechanisms controlling body size. The sma-5 mutant is very small, grows slowly and its intestinal granules look abnormal. We found a 15 kb deletion in the mutant that includes a 226 bp deletion of the 3' end of the W06B3.2-coding sequence. Based on this result, rescue experiments, RNAi experiments and a newly isolated deletion mutant of W06B3.2, we conclude that W06B3.2 is the sma-5 gene. The sma-5 mutant has much smaller intestine, body wall muscles and hypodermis than those of the wild type. However, the number of intestinal cells or body wall muscle cells is not changed, indicating that the sma-5 mutant has much smaller cells. In relation to the smaller cell size, the amount of total protein is drastically decreased; however, the DNA content of the intestinal nuclei is unchanged in the sma-5 mutant. The sma-5 gene is expressed in intestine, excretory cell and hypodermis, and encodes homologs of a mammalian MAP kinase BMK1/ERK5/MAPK7, which was reported to control cell cycle and cell proliferation. Expression of the sma-5 gene in hypodermis is important for body size control, and it can function both organ-autonomously and non-autonomously. We propose that the sma-5 gene functions in a MAP kinase pathway to regulate body size mainly through control of cell growth.


Subject(s)
Body Size/genetics , Caenorhabditis elegans Proteins/physiology , Caenorhabditis elegans/enzymology , Cell Enlargement , Mitogen-Activated Protein Kinase 7/genetics , Mitogen-Activated Protein Kinase 7/physiology , Amino Acid Sequence , Animals , Body Size/physiology , Caenorhabditis elegans/embryology , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Gene Expression , Genes, Reporter , Molecular Sequence Data , Mutation , Sequence Alignment , Structural Homology, Protein
15.
Genes Cells ; 9(9): 773-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15330854

ABSTRACT

Mechanisms involved in the control of body size are largely unknown. In the nematode C. elegans, several small body size mutants were isolated, and the responsible genes were reported to encode putative components of a TGFbeta signalling pathway. Recently, mutants in the egl-4 gene encoding cGMP-dependent protein kinases were found to have a larger body size, and it was suggested that EGL-4 down-regulates the TGFbeta/DBL-1 pathway. We show that a permeable cGMP analogue 8-Br-cGMP significantly reduces body size of the wild-type but not that of an egl-4 mutant, indicating that cGMP controls body size through EGL-4. Laser ablation of germ-line cells revealed that a germ-line signal and EGL-4 function in the same pathway. Targeted expression of EGL-4 indicates that EGL-4 can function in hypodermis, neurones and intestine both cell-autonomously and cell-nonautonomously to control organ and body size. We propose a signal cascade for the control of body size that involves a germ-line signal, cGMP, G-kinase EGL-4 and DBL-1/TGFbeta pathway. It is interesting that two important pathways involving cGMP and TGFbeta, respectively, are related. Also, the results suggest a novel mechanism for the control of organ and body size in which hypodermis plays a key role


Subject(s)
Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans/enzymology , Cyclic GMP-Dependent Protein Kinases/metabolism , Cyclic GMP/metabolism , Germ Cells/physiology , Signal Transduction , 8-Bromo Cyclic Adenosine Monophosphate/pharmacology , Animals , Caenorhabditis elegans/anatomy & histology , Caenorhabditis elegans/growth & development , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Cyclic GMP-Dependent Protein Kinases/genetics , Mutation
16.
Genes Cells ; 9(1): 39-47, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14723706

ABSTRACT

We recently showed that egl-4 mutants in Caenorhabditis elegans have a much larger body size and that the egl-4 gene encodes cyclic GMP-dependent protein kinases (G-kinases). Cell sizes, but not cell numbers, in the major organs are increased in the mutants. Genetic interaction studies suggest that EGL-4 represses the DBL-1/TGFbeta pathway that is known to control body size. To understand the mechanisms of body size control in C. elegans, we analysed sma-2, sma-4 and sma-6 small mutants in the DBL-1 pathway. The volumes of major organs were precisely determined with the method developed by us. They are significantly decreased as compared to those of the wild-type while cell numbers are not, indicating that cell size is decreased. DNA contents in the nuclei of major organs are not significantly changed in the small mutants and in an egl-4 large mutant. Total protein contents are much decreased in the small mutants and slightly increased in the egl-4 mutant. Based on these results, we propose that decreased cell and body size of the small mutants in the DBL-1/TGFbeta pathway is mainly due to decreased levels of protein expression, and that increase in fluid content is a major reason for the increase in cell and body size in egl-4 mutants.


Subject(s)
Body Constitution/physiology , Cyclic GMP-Dependent Protein Kinases/metabolism , Signal Transduction/physiology , Transforming Growth Factor beta/metabolism , Animals , Caenorhabditis elegans , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Cell Count , Cell Nucleus/genetics , Cell Nucleus/metabolism , Cyclic GMP-Dependent Protein Kinase Type I , Cyclic GMP-Dependent Protein Kinases/genetics , DNA/metabolism , Mutation , Neuropeptides/genetics , Neuropeptides/metabolism , Osmotic Pressure , Sodium Chloride/metabolism , Transforming Growth Factor beta/genetics
17.
Development ; 130(6): 1089-99, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12571101

ABSTRACT

We designed an automatic system to measure body length, diameters and volume of a C. elegans worm. By using this system, mutants with an increased body volume exceeding 50% were isolated. Four of them are grossly normal in morphology and development, grow longer to be almost twice as big, and have weak egg-laying defects and extended lifespan. All the four mutants have a mutation in the egl-4 gene. We show that the egl-4 gene encodes cGMP-dependent protein kinases. egl-4 promoter::gfp fusion genes are mainly expressed in head neurons, hypodermis, intestine and body wall muscles. Procedures to analyze morphology and volume of major organs were developed. The results indicate that volumes of intestine, hypodermis and muscle and cell volumes in intestine and muscle are increased in the egl-4 mutants, whereas cell numbers are not. Experiments on genetic interaction suggest that the cGMP-EGL-4 signaling pathway represses body size and lifespan through DBL-1/TGF-beta and insulin pathways, respectively.


Subject(s)
Body Constitution/genetics , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans/physiology , Cyclic GMP-Dependent Protein Kinases/genetics , Cyclic GMP/metabolism , Longevity/genetics , Amino Acid Sequence , Animals , Caenorhabditis elegans/genetics , Gene Expression Profiling , Green Fluorescent Proteins , Luminescent Proteins/genetics , Molecular Sequence Data , Mutation , Recombinant Fusion Proteins/genetics
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