The protein kinase C (PKC) family is a group of serine/threonine kinases that mediate intracellular signaling activated by growth factor receptors, tyrosine kinase receptors, and G-protein coupled receptors through lipid-derived secondary messengers. In mammals, the PKC family is composed of the following three structurally and functionally distinct subgroups: conventional PKCs (cPKC; α, βI/II, and γ), novel PKCs (nPKC; δ, ε, η, and θ), and atypical PKCs (aPKC; ζ and ι/λ; λ in mice). Among the PKC family members, aPKCs play essential roles in establishing epithelial cell polarity by interacting with partition-defective (Par) proteins, Par3 and Par6, which were first identified in genetic screening for regulators of asymmetric division in the early embryo of Caenorhabditis elegans. The aPKC-Par3-Par6 ternary complex is evolutionarily conserved and is implicated in a variety of cell polarity events. To clarify functional differences between aPKCζ and aPKCλ in the stratified epidermis in vivo, we have generated mutant mice with genetic deletion of each aPKC isoform. Epidermis-specific aPKCλ conditionally knockout mice (aPKCλ cKO) showed progressive hair loss, abnormal hair cycling, a gradual decrease of hair follicle stem cell (HFSC) population, and loss of the HFSC quiescence. In addition, cutaneous wound healing was significantly retarded in aPKCλ cKO mice, and the correct orientation of cell protrusions toward the wound was disrupted in aPKCλ-deleted keratinocytes, through the destabilization of Par6β. Conversely, HFSC maintenance, wound healing, and directional cell migration in aPKCζ-deleted mice were comparable to those in their control littermates. These results indicate that aPKCs are not functionally equivalent; aPKCλ, but not aPKCζ, plays a primary role in maintaining HFSC population and cutaneous wound healing.
Spontaneous preterm birth is a syndrome caused by infection, inflammation, ischemia, or bleeding and its mechanisms are largely unexplored. Strategies to prevent preterm birth include avoiding risk factors as much as possible and medications such as tocolytics. The main risk factors for preterm birth include a history of preterm birth, shortened cervical length, history of cervical surgery, pre-pregnancy weight loss, poor weight gain during pregnancy, and smoking. Typical tocolytics include ritodrine hydrochloride and magnesium sulfate. The use of continuous infusion of low-dose ritodrine hydrochloride is more frequent in Japan than in the United States (US) and in Europe. Ritodrine hydrochloride has been used in relatively large quantities and on a short-term basis in the US and in Europe. A number of randomized controlled trials (RCTs) have been performed regarding the large quantities and the short-term methods frequently employed in the US and in Europe. They showed that ritodrine hydrochloride had limited efficacy and many side effects, which led to the limited use of ritodrine hydrochloride and beta-stimulants in the US and in Europe. RCTs have not been performed regarding low-dose continuous infusions frequently employed in Japan. Hence, the evidence for this method has not been established. In recent years, the use of ritodrine hydrochloride has decreased substantially in Japan due to the restrictions on the use of beta-stimulants in the United States and in Europe. In addition, progesterone administration has been established in other countries as a method of preventing preterm birth in cases of shortening of the cervical length, and it is being considered in Japan.
The treatment methods prevalent in Japan differ in some aspects from those in Europe and in the US. The lower preterm birth rate in Japan compared to other countries suggests that this difference in treatment methods may be justified. Recent studies have shown that progesterone significantly reduces preterm birth rates. Its indications in Japan should be carefully considered for its appropriate use. More research should be conducted to reduce preterm births in the future.
Multiple intravenous drugs are often combined in the same tubing, syringe, or bottle, which greatly increases the risk of drug incompatibility. Providing information on avoiding drug incompatibilities is an important task for pharmacists and other medical staff. Techniques to avoid incompatibility include changing the administration schedule, flushing with normal saline before and after injection, and administering drugs by using separate lines. In our hospital, the drug information (DI) pharmacist uses ordering and departmental systems to provide information on avoiding drug incompatibilities when a physician prescribes an injection or a nurse prepares an injection based on a prescription. In addition, to avoid drug incompatibilities of continuous injectables, we developed a compatibility chart for 27 drugs. To facilitate its use by medical staff, the chart has been placed in injection preparation areas in each ward. In addition, the ward pharmacist checks and provides an appropriate intravenous line at the bedside. In conclusion, DI pharmacists should establish a system for avoiding drug incompatibilities, and drug infusion routes should be managed by ward pharmacists.
The majority of childhood intussusceptions have idiopathic causes, but 2.7% are due to an underlying disease, of which 5.5% can be attributed to malignant lymphoma. Age is an important factor in the onset of pathologically-related intussusceptions. We report a case in a 15-year-old boy who visited a prior hospital with a chief complaint of sudden-onset severe abdominal pain. Computed tomography revealed intussusception, and the patient was transferred to our hospital within several hours, where high-pressure enema reduction was performed. The ileocecum blockage could not be removed even after multiple high-pressure enemas, so emergency surgery was planned. Intraoperatively, dilation was observed at the terminal ileum, and a hard-mass tumor was palpated in the ileocecum. The ileocecal region containing the mass was excised. A diagnosis of diffuse large B-cell lymphoma was made on the basis of pathological examination, and chemotherapy was initiated. The patient has remained in remission for 2 years and is in good condition. The probability of an underlying diseases increases with age. Adolescent intussusception is often discovered due to the onset of acute abdomen and requires emergency surgery even in the absence of a prior diagnosis. The development of intussusception might be the first sign of malignant disease. In older children who have underlying diseases, as in this case, it is difficult to perform high-pressure enema reductions, even shortly after onset. In cases of intussusception in older pediatric patients, it is necessary to consider the possibility of an underlying disease and carry out early investigations accordingly.
Peripheral aneurysms with moyamoya disease are known to be a source of intracranial hemorrhage; they either disappear spontaneously or re-bleed repeatedly. There is no consensus on treatment for these aneurysms. We report a case of ruptured peripheral cerebral aneurysm in abnormal vessels associated with moyamoya disease in a 36-year-old man who presented with intraparenchymal hemorrhage in genu of the corpus callosum associated with intraventricular extension and thin subarachnoid hemorrhage. Cerebral angiography showed a saccular aneurysm (2.5 mm maximum diameter) with a daughter sac at right A2/A3, occlusion of the supraclinoid portion of the left internal carotid artery, and abundant ipsilateral moyamoya vessels. On day 17, we performed aneurysmal neck clipping. After surgery, neither symptomatic cerebral vasospasm nor hydrocephalus occurred. The patient was discharged without any neurological deficits. Some peripheral cerebral aneurysms associated with moyamoya disease regress spontaneously, whereas others may show rebleeding. Surgical treatment should be considered if the aneurysm expands, or at least does not shrink, on imaging.
There have been various reports of treatment methods for quadriceps tendon rupture. However, there are very few reports regarding surgical repair for quadriceps muscle rupture. We report a case of old quadriceps muscle rupture treated with surgical repair. A 20-year-old man underwent muscle suturing using perimeter sutures and modified Mason-Allen sutures for a painful old subcutaneous rupture of rectus femoris muscle. After surgery, the pain disappeared and the quadriceps muscle strength improved, and he returned to sports 6 months after the operation. This method provided sufficient muscle strength without need for special instrumentation or procedure, and was effective for his old rectus femoris rupture.