Analysis of reference values of serum S100B concentrations of Japanese adults

PURPOSE: S100B is a calcium-binding protein which exists in abundance in glial cells of the central nervous system (CNS). It is reported that the serum S100B level increase with various CNS diseases, such as stroke, head injury, schizophrenia, major depression and Alzheimer's disease. However, there are no reports on its reference values for the Japanese. The purpose of this study is to know the serum S100B concentrations of Japanese adults, free of any CNS diseases, according to sex, age and circadian rhythm. Moreover, the stability and reproducibility of its measurements of S100B in frozen serum over 7 months. METHODS: Volunteers were 26 male and 25 female of Japanese adults. Venous blood samples were collected at given times of a day and serum was obtained by centrifugation at 4 degrees C. An automated chemiluminescence analyzer "LIAISON" and exclusive reagent Sangtec 100 (DiaSorin, Italy), was used for measurement of serum S100B concentrations. RESULTS: The serum S100B concentrations in Japanese adults corresponded well, with the reported values in Asians. Differences by age and sex were not found. S100B did not how circadian variation. The serum S100B concentrations measured in two months and in nine months after venipuncture were almost the same. CONCLUSION: The measurement of S100B by "LIAISON" showed excellent reproducibility and reliability. Furthermore, stability of serum S100B stored at -80 degrees C was good.     

Transplantation of neural cells derived from retinoic acid-treated cynomolgus monkey embryonic stem cells successfully improved motor function of hemiplegic mice with experimental brain injury

We induced neural cells by treating cynomolgus monkey embryonic stem (ES) cells with retinoic acid. The treated cells mainly expressed betaIIItubulin. They further differentiated into neurons expressing neurofilament middle chain (NFM) in elongated axons. Half of the cells differentiated into Islet1+ motoneurons in vitro. The monkey ES-derived neural cells were transplanted to hemiplegic mice with experimental brain injury mimicking stroke. The neural cells that had grafted into periventricular area of the mice distributed extensively over the injured cortex. Some of the transplanted cells expressed the neural stem/progenitor marker nestin 2 days after transplantation. The cells expressed markers characteristic of mature motoneurons 28 days after transplantation. Mice with the neural cell graft gradually recovered motor function, whereas control animals remained hemiplegic. This is the first demonstration that neural cells derived from nonhuman primate ES cells have the ability to restore motor function in an animal model of brain injury.     

Detection of ehrlichial DNA in small rodents captured in a woodland area of Hokkaido, the northernmost island of Japan, where Lyme disease is endemic

The ehrlichial gene was detected in small rodents trapped in a Lyme disease-endemic area in Hokkaido, the northernmost island of Japan. Primer pairs of 16S rDNA targeting the genus Ehrlichia and other regions of the 16S rDNA specific for E. chaffeensis and E. muris were used for identification. The DNA fragment specific for 16S rDNA of Ehrlichia spp. was detected in 4 of 94 Apodemus speciosus mice (positive rate: 4.3%) and 5 of 73 Clethrionomys rufocanus bedfordiae mice (positive rate: 6.8%). The nucleotide sequence of the amplified 16S rDNA fragment was most similar to those of E. muris-like Ehrlichia, Ehrlichia spp. HF565 and Shizuoka-36, originating in the northern and central parts of Japan. In phylogenetic analysis based on 16S rDNA sequences, the northern, central and western groups of E. muris-like Ehrlichia from a cluster with microorganisms of the E. muris group. These results suggest that there are a group of E. muris microorganisms and a group of E. muris- like microorganisms in Japan.     

A critical increase in right-to-left shunt after acute myocardial infarction in a 68-year-old male with tetralogy of Fallot

A male patient with tetralogy of Fallot accompanied by aortic regurgitation had maintained sufficient exercise capacity for a number of decades with the status of acyanotic tetralogy of Fallot. When he was 67 years old, he suffered a posterior wall acute myocardial infarction and direct percutaneous coronary angioplasty successfully revascularised the target lesion in the left circumflex artery. However, a few months after the onset of the myocardial infarction, his shortness of breath became clinically significant and was associated with increased right-to-left shunt and increased right ventricular end-diastolic pressure, as well as hypoxia. At 68 years old, therefore, total corrective repair of the tetralogy with replacement of the aortic and pulmonary valves was performed. The patient was asymptomatic after the successful operation. This report suggests that coronary artery disease can be one of the potential factors in inducing critical hemodynamic changes in aging patients with congenital heart disease, especially those who have a shunt between the right and left chambers. The unique clinical course is described with some discussion of the repair of tetralogy in adults.     

Grafting of glial cell line-derived neurotrophic factor secreting cells for hypoxic-ischemic encephalopathy in neonatal rats

OBJECTIVE: It has been reported that an infarcted area is reduced by the injection of glial cell line-derived neurotrophic factor into brain parenchyma after hypoxic/ischemic insult in neonatal rats. For use of glial cell line-derived neurotrophic factor in humans, we have developed a system for the delivery of a constant supply of glial cell line-derived neurotrophic factor to the brain. The aim of this study was to examine the neuroprotective effect of glial cell line-derived neurotrophic factor with the use of this delivery system. STUDY DESIGN: Baby hamster kidney cells were transfected with human glial cell line-derived neurotrophic factor complementary DNA, encapsulated in semipermeable hollow fibers, and implanted into the left cerebrum of 12-day-old Wistar rats (glial cell line-derived neurotrophic factor group, 11 rats). Nontransfected baby hamster kidney cells served as controls (control group, 9 rats). Two days after implantation, the rats received a hypoxic/ischemic stress, with a modification of Levine's method. Seven days later the rats were killed, and coronal brain slices were cut 2, 4, 6, 8, and 10 mm from the anterior pole. The cortex, hippocampus, striatum, and thalamus were evaluated for damage severity. The serum concentrations of glial cell line-derived neurotrophic factor were also determined. RESULTS: The left brain hemispheric area was significantly larger; the neuronal damage to each brain region was significantly less, and the serum glial cell line-derived neurotrophic factor concentrations were significantly higher in the glial cell line-derived neurotrophic factor group, compared with the control group. CONCLUSION: Grafting of encapsulated glial cell line-derived neurotrophic factor-secreting cells is a promising way to protect the neonatal brain from hypoxic/ischemic insult.     

Clinical significance of anti-phosphatidylserine-prothrombin complex antibodies in antiphospholipid syndrome

We clarified the clinical significance of IgG anti-phosphatidylserine-prothrombin complex (PS-PT) antibodies in the antiphospholipid syndrome (APS). The study population consisted of 122 patients with SLE and lupus-like disease. IgG anti-PS-PT antibodies were detected in 44% of 59 patients according to the diagnostic criteria by Harris and Hughes. This frequency was significantly (p < 0.005) higher than the 14% seen in patients without APS. IgG anti-PS-PT antibodies were strongly (p < 0.005) associated with thrombosis. In addition, IgG anti-PS-PT antibodies were positive in 64% of IgG beta2-GPI dependent anti-cardiolipin antibody negative APS patients under the Sapporo criteria. The above findings indicate that IgG anti-PS-PT antibodies as well as beta2,-GPI dependent anti-cardiolipin antibodies should be examined in the diagnosis of APS.     

Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates

OBJECTIVES: We investigated the role of P-selectin in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates. BACKGROUND: Plaque rupture followed by thrombus formation is a fundamental pathophysiology of acute coronary syndromes. Although the adhesive interaction between platelets and leukocytes via P-selectin is known to mediate platelet-rich thrombi, the true function of P-selectin in thrombus formation in vivo is unknown. METHODS: In wild-type (P(+/+)) and P-selectin-deficient (P(-/-)) mice with ferric chloride (FeCl(3))-induced carotid arterial thrombosis model, we measured in vivo platelet P-selectin expression and adenosine diphosphate (ADP)-induced ex vivo platelet aggregation. We also measured ex vivo ADP-induced whole blood aggregations and their size distribution by flow cytometry. RESULTS: Time to thrombotic occlusion was longer in P(-/-) mice than in P(+/+) mice. Spontaneous reflow after total thrombotic occlusion was observed in 8 of 10 P(-/-) mice but not in any P(+/+) mice. ADP-induced ex vivo platelet aggregation was not different between the two groups. However, ADP-induced ex vivo whole blood aggregation was inhibited in P(-/-) mice compared to P(+/+) mice. FeCl(3) application increased in vivo expressions of platelet P-selectin in P(+/+) mice but not in P(-/-) mice. The number of leukocytes within thrombi was less in P(-/-) mice than in P(+/+) mice. In flow cytometric analysis of size distribution of ADP-induced whole blood aggregates, the number of large aggregates was less in P(-/-) mice than in P(+/+) mice. Using platelet and leukocyte fluorescence makers, the large aggregates were confirmed as platelet-leukocyte aggregates. CONCLUSIONS: Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates.