An analysis was performed of 2,168 consecutive stroke patients who were examined by computed tomography and entered into a hospital-based stroke registry in Akita Prefecture, Japan. The occurrence of cerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage was 30, 55, and 14%, respectively. Age-specific rates of subarachnoid hemorrhage were higher in women than men; other types of stroke showed a preponderance in men. Total strokes increased in the winter; this seasonal difference was confined to cerebral hemorrhage. Putaminal hemorrhages predominated in the younger age groups; thalamic hemorrhage and cerebellar hemorrhage were predominant in the older age groups. The increased accuracy of the diagnosis of stroke subtypes by the use of computed tomography in this study is in contrast to other community-based epldemiologic studies that have relied solely on clinical diagnosis. This increased accuracy is seen to be the reason that new ratios of stroke subtype incidence have been identified. (Stroke 1987;18:402-406) T HE World Health Organization coordinated a collaborative study of stroke incidence in 17 centers from developing and developed countries between 1971 and 1974.' The Japanese centers participating were found to have the highest age-adjusted stroke incidence rates of the 17 centers in the study. Among all these centers, Akita, Japan showed the highest incidence rate for stroke. In epidemiologic studies, diagnosis of stroke is usually based on clinical judgment. The accuracy of clinical diagnoses is known to be rather high, 23 but misdiagnosis can reach 20-30% 4 in pathologic subtypes of stroke (i.e., cerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage, SAH). Because misdiagnosis of subtypes distorts the results in epidemiologic studies of stroke and because computed tomography (CT) provides highly accurate diagnoses, 5 the Akita medical community has confirmed most stroke patients in recent years by CT, and since 1983 has set up a hospitalbased stroke registry of patients confirmed by CT. This paper analyzes the diagnoses in the stroke registry in Akita and compares them with the results of previous community-based epidemiologic studies of the subtypes of stroke. Subjects and MethodsAll strokes diagnosed by CT from November 1, 1983 to May 31, 1985 were included in the present study. Twenty-four hospitals, encompassing all instiFrom the doctors group of clinico-epidemiological study for stroke, Akita.Address for reprints: Kazuo Suzuki, MD, Department of Epidemiology, Research Institute of Brain and Blood Vessels-Akita, 6-10, Senshu-Kubota-Machi, Akita 010, Japan.Received May 15, 1986; accepted November 5, 1986. tutes using CT in Akita Prefecture, participated. Stroke was defined as the onset of rapidly developing clinical signs of focal or global disturbance of cerebral function, lasting more than 24 hours or leading to death, with no apparent cause other than a vascular origin. Recurring attacks were included. All cases were examined using CT within 3 weeks of the onset...

Recent research has shown that reparative (alternatively activated or M2) macrophages play a role in repair of damaged tissues, including the infarcted hearts. Administration of IL-4 is known to augment M2 macrophages. This translational study thus aimed to investigate whether IL-4 administration is useful for the treatment of myocardial infarction. Long-acting IL-4 complex (IL-4c; recombinant IL-4 mixed with anti-IL-4 monoclonal antibody as a stabilizer) was administered after coronary artery ligation in mice. It was observed that IL-4c administration increased accumulation of CD206+F4/80+ M2-like macrophages predominantly in the injured myocardium, compared to the control. Sorted cardiac M2-like macrophages highly expressed wide-ranging tissue repair-related genes. Indeed, IL-4c administration enhanced cardiac function in association with reduced infarct size and enhanced tissue repair (strengthened connective tissue formation, improved microvascular formation and attenuated cardiomyocyte hypertrophy). Experiments using Trib1 −/− mice that had a depleted ability to develop M2 macrophages and other in-vitro studies supported that these IL-4-mediated effects were induced via M2-like macrophages. On the other hand, when administered at Day 28 post-MI, the effects of IL-4c were diminished, suggesting a time-frame for IL-4 treatment to be effective. These data represent proof-of-concept of efficacy of IL-4 treatment for acute myocardial infarction, encouraging its further development.

Mammalian transcriptome analysis has uncovered tens of thousands of novel transcripts of unknown function (TUFs). Classical and recent examples suggest that the majority of TUFs may underlie vital intracellular functions as non-coding RNAs because of their low coding potentials. However, only a portion of TUFs have been studied to date, and the functional significance of TUFs remains mostly uncharacterized. To increase the repertoire of functional TUFs, we screened for TUFs whose expression is controlled during differentiation of pluripotent human mesenchymal stem cells (hMSCs). The resulting six TUFs, named transcripts related to hMSC differentiation (TMDs), displayed distinct transcriptional kinetics during hMSC adipogenesis and/or osteogenesis. Structural and comparative genomic characterization suggested a wide variety of biologically active structures of these TMDs, including a long nuclear non-coding RNA, a microRNA host gene and a novel small protein gene. Moreover, the transcriptional response to established pathway activators indicated that most of these TMDs were transcriptionally regulated by each of the two key pathways for hMSC differentiation: the Wnt and protein kinase A (PKA) signaling pathways. The present study suggests that not only TMDs but also other human TUFs may in general participate in vital cellular functions with different molecular mechanisms.