CSF phosphorylated tau protein and mild cognitive impairment: a prospective study

Cerebrospinal fluid (CSF) tau protein phosphorylated at both Thr231 and Ser235 sites (CSF/phospho-tau(231-235)) and total tau (CSF/total-tau) were quantified by sandwich ELISA in 20 patients with mild cognitive impairment (MCI) who eventually developed AD on follow-up as well as seven memory complainers with no objective memory loss. 13/20 (65%) of the MCI patients had high CSF/total-tau and detectable levels of CSF/phospho-tau(231-235), whereas these markers were low and under a detectable level in all of the memory complainers. Although either a total-tau, phospho-tau measurement or a combination of these can help in predicting if MCI will develop AD, our results suggest that the pathogenic steps of AD may be at the stage that finally leads to an accumulation of abnormally phosphorylated tau and neuron death, at least in some brain areas, when MCI patients present with the earliest detectable clinical symptoms of dementia.     

The influence of human T lymphotropic virus type I infection on the outcome of cardiovascular surgery

OBJECTIVE: Human T lymphotropic virus type I infects CD4(+) T cells and affects cell-mediated immunity. Cardiopulmonary bypass transiently alters lymphocyte subsets, resulting in a reduction in CD4(+) T cells and an increase in CD8(+) T cells. We proposed that cardiovascular operations and human T lymphotropic virus type I infection may act synergistically, resulting in serious damage to cell-mediated immunity. METHODS: A total of 517 consecutive patients who were preoperatively screened for anti-human T lymphotropic virus type I antibody and underwent cardiovascular operations with cardiopulmonary bypass were enrolled in this study. Of the 517 patients, 82 (16%) had positive test results for anti-human T lymphotropic virus type I antibody. The surgical outcome of patients with positive and negative results for anti-human T lymphotropic virus type I antibody was analyzed retrospectively. RESULTS: There was no difference between the 2 groups with respect to early mortality. Distribution of survival curve was also not significantly different (P =.5; mean follow-up duration, 2.4 +/- 1.8 years [range, 0-9.4 years] and 3.2 +/- 2.8 years [range, 0-9.8 years]) in the groups with positive and negative antibody results, respectively). In particular, long-term follow-up did not reveal adult T-cell leukemia or human T lymphotropic virus type I-associated myelopathy, and occurrence of neoplasm did not differ between groups. Early infectious complication was, however, significantly higher in the group with positive antibody results than in the group with negative results (P =.02). Logistic regression analysis revealed human T lymphotropic virus type I infection as a significant risk for this complication (P =.04; odds ratio, 2.5; 95% confidence interval, 1. 0-5.8). CONCLUSION: A combination of human T lymphotropic virus type I infection and cardiovascular operation is believed to increase the potential risk of infectious complications shortly after the operation. However, this synergistic effect seems to be transient and has little influence on long-term prognosis.     

Caffeine induces apoptosis of human umbilical vein endothelial cells through the caspase-9 pathway.

Caffeine is known to modulate placental and fetal umbilical circulation. It is demonstrated that apoptosis of human umbilical vein endothelial cells (HUVECs) is associated with placental umbilical vascular diseases. The present study was conducted to investigate the effects of caffeine on apoptosis of HUVECs. Isolated HUVECs were cultured under serum-free conditions for 24 h, and then treated with graded concentrations of caffeine (30, 100 and 300 microM) for additional 24 h and 48 h. The number of viable HUVECs was determined by cell counting. Apoptotic HUVECs were assessed by Hoechst33342 dye staining. The expression of caspase-9, caspase-8, caspase-3 and poly(ADP-ribose) polymerase (PARP) was assessed by Western blot analysis. Caffeine induced a dose- and time-dependent decrease in the number of viable HUVECs. Caffeine at concentrations higher than 100 microM significantly increased the percentage of apoptotic HUVECs. Caffeine at concentrations higher than 100 microM significantly increased cleaved caspase-9, caspase-3 and PARP expression in HUVECs at 24-h treatment compared with untreated cultures, whereas 30 microM caffeine significantly increased only caspase-3 expression at 24 h. Caffeine did not affect cleaved caspase-8 expression at 48 h. These results suggest that high concentrations of caffeine inhibit cell growth of HUVECs and induce apoptosis through the caspase-9 pathway.     

Operation for adult patent ductus arteriosus using cardiopulmonary bypass

Background. Surgical repair of adult patent ductus arteriosus is more hazardous than when performed on young patients.

Methods. Nine adult patent ductus arteriosus patients underwent surgical repair between January 1986 and December 1998. There were 3 male and 6 female patients (mean age 55.0 years). The ratio of pulmonary blood flow to systemic flow was 2.40 ± 0.95, and pulmonary arterial pressure was 56.0 ± 26.4 mm Hg. The operation was performed using transpulmonary approach under total cardiopulmonary bypass. Balloon occlusion method was also utilized.

Results. Direct closure was made in 5 and patch closure in 4 patients. Cardiopulmonary bypass and balloon occlusion were safely established. Cardioplegic arrest was not required in the 2 most recent patients. No operative death has occurred. Pulmonary arterial systolic pressure decreased to 35.3 ± 6.6 mm Hg at 6 months after operation. The mean follow-up period for all patients is 55 months. To date, neither recannalization of the ductus nor pseudoaneurysm has been recognized.

Conclusions. Cardiopulmonary bypass with balloon occlusion provides a safe operation for adult patients with complicated patent ductus arteriosus.     

A case of fixed drug eruption due to ephedrine hydrochloride

We report the case of a 29-year old female who developed a fixed drug eruption due to ephedrine hydrochloride administered intravenously during the cesarean section. On the day of the operation a palm-sized dark brown macula with half egg-sized erosion appeared on her right lower thigh. We diagnosed her disease as fixed drug eruption and examined the causative agent among all the 14 drugs used from admission to the appearance of fixed drug eruption. Each of systemic challenge, patch test on the lesion, intradermal and subcutaneous injection on the lesion with ephedrine hydrochloride showed positive reaction. As far as we have been able to search, our case is the first one of fixed drug eruption due to ephedrine hydrochloride.     

Improved trends in survival and engraftment after single cord blood transplantation for adult acute myeloid leukemia

Unrelated cord blood transplantation (CBT) is an alternative curative option for adult patients with acute myeloid leukemia (AML) who need allogeneic hematopoietic cell transplantation (HCT) but lack an HLA-matched related or unrelated donor. However, large-scale data are lacking on CBT outcomes for unselected adult AML. To investigate the trends of survival and engraftment after CBT over the past 22 years, we retrospectively evaluated the data of patients with AML in Japan according to the time period of CBT (1998–2007 vs 2008–2013 vs 2014–2019). A total of 5504 patients who received single-unit CBT as first allogeneic HCT for AML were included. Overall survival (OS) at 2 years significantly improved over time. The improved OS among patients in ≥ complete remission (CR)3 and active disease at CBT was mainly due to a reduction of relapse-related mortality, whereas among patients in first or second CR at CBT, this was due mainly to a reduction of non-relapse mortality. The trends of neutrophil engraftment also improved over time. This experience demonstrated that the survival and engraftment rate after CBT for this group has improved over the past 22 years.Subject terms: Acute myeloid leukaemia, Cancer immunotherapy     

A device for adsorbing unbound, unconjugated bilirubin and its effects in vitro and in a hyperbilirubinemic newborn piglet

AIMS: A novel blood purification material that we previously reported as a superantigen- and cytokine-adsorbing device (SCAD) was evaluated for its ability to adsorb unbound, unconjugated bilirubin (UUBil) in vitro and in vivo. METHODS: In albumin-containing buffer, UUBil was dissolved and circulated through the SCAD column. Also, bilirubin was infused into low-body weight newborn piglets and hemoperfused for 3 h over SCAD columns. RESULTS: In albumin-containing buffer, concentration of bilirubin decreased from 34 to 0.6 mg/dL within 5 h and the SCAD fiber turned brown, indicating that bilirubin was adsorbed onto the surface of the adsorbent and was not degraded during the circulation. Using the hyperbilirubinemia swine, clearances of total bilirubin (TBil), direct bilirubin (DBil), and indirect bilirubin (IdBil) were significantly higher (P<0.01) in the SCAD group compared with the control group. The clearances of TBil, DBil, and IdBil at 3 h after the initiation of the bilirubin infusion were 0.47, 0.53, and 0.45 mL/min, respectively, at a blood flow rate of 2.5 mL/min, and this result indicates that almost 20% of bilirubins were adsorbed to the SCAD column in a single passage. CONCLUSION: These results provide initial evidence that SCAD treatment is effective in the removal of UUBil and can be performed safely in newborn animals.     

Studies on rennin as a virus-model. II. resemblance of rennin to some viruses in its physical and chemical properties

Summary Rennin is regarded as being similar to viruses such as vaccinia and phage in its physical and chemical properties. Rennet activity is carried by a lipoprotein existing in particles or micells of very great dimensions.Coagulation of milk by rennin can be considered to be a chain reaction to some extent.     

Resorption and excretion of glucose by the particle of minute-body-forming proteid,including virus proteid

Summary The resorption and excretion of glucose by living cells can be explained to be due to a property of the minute-body-forming proteid existing in the cells.Also in this property, there is no difference between virus proteid (vaccinia) and the normal minute-body-forming proteid having no virus action.