Characterization of compound missense mutation and deletion of carnitine palmitoyltransferase II in a patient with adenovirus-associated encephalopathy

Background : In mammals, carnitine palmitoyltransferase (CPT) system is a pivotal component of energy metabolism through mitochondrial fatty acid oxidation. The majority of patients with fatal or handicapped influenza-associated encephalopathy exhibit thermolabile compound homo/heterozygous mutations of CPT II. Objective : Compound CPT II mutations, [c.647A G (p.Q216R)], [c.1102G A (p.V368I)], [c.1939A G (p.M647V)] and [c.745delG (p.G249EfsX16)], were found in a patient with adenovirus-associated encephalopathy and his family. The properties of these CPT II mutations were analyzed in COS-7 cells. Methods : CPT II mutations in the patient and his family were expressed in COS-7 cells and their molecular masses, enzyme activities, thermal instabilities and halflives were analyzed. Results : We identified two novel CPT II mutations in the patient, [c.647A G (p.Q216R)] and [c.745delG (p.G249EfsX16)]. The CPT II Q216R mutation showed mild reduction of activity, thermal instability and short half-life but compound mutations with Q216R+V368I+M647V showed further enhancement of these disabilities, although mutations V368I and M647V had no such effects. CPT II mutation [c.745delG (p.G249 EfsX16)] abolished enzyme activity and showed short half-life. Conclusion : The thermal instability and short half-life of the novel CPT II mutations, [c.647A G (p.Q216R)] and [c.745delG (p.G249EfsX16)], could play important roles in energy crisis in the pathogenesis of virus-associated encephalopathy

Tuning of Sry expression by H3K9 methylation and demethylation

Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the Sry locus in embryonic gonads, thereby compromising Sry expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the Sry locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct Sry expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the Sry locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous GLP mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring Sry expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of Sry expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance

看護師のアピアランスに関する認識

This study aimed to clarify recognition about the appearance of nurses in an acute stage hospital and contribute to effective spread and enlightenment for maintenance of the appearance support system. The authors performed a questionnaire survey with the items such as interest in appearance care, start period, participants for care, enforcers, support resource and so on for １８３ nurses with cancer nursing experience who worked at hospitals in local cities that were bases for cancer treatment cooperation. The result revealed that a number of participants interested in appearance care and most of them recognized that appearance care should start at the time of cancer examination or before treatment. Moreover, it has been indicated that the nurses who were highly concerned with appearance care from a wider perspective including patients’ psychological conditions. The result has suggested that it is necessary to promote “care to prepare in anticipation of change in physical appearance” on the basis of the characteristic of acute stage hospitals and establish an individual support system in accordance with the conditions of the nurses’ interest in appearance for maintenance of the appearance support system

First Japanese Case of Carnitine Palmitoyltransferase II Deficiency with the Homozygous Point Mutation S113L

Carnitine palmitoyltransferase II (CPT II) deficiency is a rare inherited disorder related to recurrent episodes of rhabdomyolysis. The adult myopathic form of CPT II deficiency is relatively benign and difficult to diagnose. The point mutation S113L in CPT2 is very common in Caucasian patients, whereas F383Y is the most common mutation among Japanese patients. We herein present a case of CPT II deficiency in a Japanese patient homozygous for the missense mutation S113L. The patient showed a decreased frequency of rhabdomyolysis recurrence after the administration of a diet containing medium-chain triglyceride oil and supplementation with carnitine and bezafibrate

Family Caregiving in Japan: The Influence of Cultural Constructs in the Care of Adults with Cancer

Caring culture is a concept embodying the perceptions and caring practices of caregivers, acknowledging the unique role of cultural beliefs in shaping behavior. A qualitative descriptive study with 13 caregivers of adult family members with a cancer diagnosis in Japan was conducted to gain insight into perceptions and experiences surrounding caregiving. Several major categories were identified, representing rarely reported cultural constructs of high cultural value for the Japanese: On—repayment for what the patient has given, Caregiving as performing a socially expected role, Enryo/meiwaku—restraint in asking for help, Family decision making reflecting strong bonds, Omoiyari—empathizing with the patient’s feelings, and Inori—praying to myriad gods and ancestors. The Japanese cultural construct of ie (the strong relationship to family lineage and spiritual connection to past and future generations) is helpful in understanding these categories. Invisible yet powerful cultural constructs permeated caregiving practices. Insights from Japanese cultural concepts and beliefs may foster sensitivity and individualized care in diverse settings, cultures, and societies

Rescuing the aberrant sex development of H3K9 demethylase Jmjd1a-deficient mice by modulating H3K9 methylation balance

<div><p>Histone H3 lysine 9 (H3K9) methylation is a hallmark of heterochromatin. H3K9 demethylation is crucial in mouse sex determination; The H3K9 demethylase Jmjd1a deficiency leads to increased H3K9 methylation at the <i>Sry</i> locus in embryonic gonads, thereby compromising <i>Sry</i> expression and causing male-to-female sex reversal. We hypothesized that the H3K9 methylation level at the <i>Sry</i> locus is finely tuned by the balance in activities between the H3K9 demethylase Jmjd1a and an unidentified H3K9 methyltransferase to ensure correct <i>Sry</i> expression. Here we identified the GLP/G9a H3K9 methyltransferase complex as the enzyme catalyzing H3K9 methylation at the <i>Sry</i> locus. Based on this finding, we tried to rescue the sex-reversal phenotype of Jmjd1a-deficient mice by modulating GLP/G9a complex activity. A heterozygous <i>GLP</i> mutation rescued the sex-reversal phenotype of Jmjd1a-deficient mice by restoring <i>Sry</i> expression. The administration of a chemical inhibitor of GLP/G9a enzyme into Jmjd1a-deficient embryos also successfully rescued sex reversal. Our study not only reveals the molecular mechanism underlying the tuning of <i>Sry</i> expression but also provides proof on the principle of therapeutic strategies based on the pharmacological modulation of epigenetic balance.</p></div