Effects of calcium in continuous cardioplegia on myocardial protection

The effects of calcium (Ca) on a hyperkalemic cardioplegic solution for continuous cardioplegia were examined in an isolated perfused working rat heart model. The coronary arteries were perfused with a modified Krebs-Henseleit bicarbonate buffer (K-H) solution, containing various concentrations of Ca(0.1, 0.6, 1.2, and 2.5 mmol/l) and a high concentration of potassium (20 mmol/l), for 180 min, after which cardiac arrest was induced at 37°C for 180 min. Cardiac function and creatine kinase (CK) were measured. In the control group, K-H solution was infused in place of the cardioplegic solution, and cardiac arrest was not induced. No significant differences were observed between the groups infused with the K-H solution containing Ca concentrations of 0.6, 1.2, and 2.5 mmol/l in the percent recovery of aortic flow (82.1±2.9%, 80.6±2.0%, and 71.5±3.7% (mean±SEM) respectively) or in the recovery of other indices of cardiac function, or in CK leakage. There were also no significant differences in the recovery of cardiac function and CK leakage between these groups and the control group. In the Ca 0.1 mmol/l group, however, the characteristic Ca paradox was observed. These findings suggest that if the Ca concentration in a cardioplegic solution is higher than 0.6 mmol/l during continuous cardioplegia, excellent cardioprotective effects will be achieved.     

Variation of the conserved neutralizing epitope in influenza B virus victoria group isolates in Japan

For almost 20 years, the neutralizing-epitope site specific for influenza B virus Victoria group isolates was conserved at the "tip" of the hemagglutinin molecule; however, it was not detected in half of the isolates from the 2002-2003 epidemic in Japan. Amino acid substitutions (D164E or N165K) were observed at the "tip", and the epitope was altered. The viral antigenicities were affected, and human antibodies did not substantially inhibit the hemagglutination in the hemagglutination inhibition tests. It is suspected that such variants will be important in future epidemics.     

CUSHING'S SYNDROME WITH BILATERAL MULTINODULAR ADRENAL HYPERPLASIA

An unusual case of Cushing's syndrome of a 59-year-old man with bilateral multinodular adrenal hyperplasia and microadenoma of the pituitary gland is presented. Failure to suppress plasma Cortisol with large doses of dexamethasone may suggest autonomous growth of hyperplastic nodules of the adrenals, which were at first induced by prolonged stimuli of ACTH from the microadenoma of the pituitary gland. ACTH could not be detected in the microadenoma cells on paraffin sections, while Crooke's cells were strongly positive for ACTH. The interrelation between bilateral multinodular adrenal hyperplasia and pituitary microadenoma is discussed.     

The vomeronasal chemosensory system as a route of neuroinvasion by herpes simplex virus

We have investigated the potential of neurotropic microbes to invade the central nervous system (CNS) via the peripheral nervous system. Herpes simplex virus type 1 (HSV-1) strain KH6 and herpes simplex virus type 2 (HSV-2) strain 186 were found to infect chemosensory neurons in the vomeronasal organ (the pheromone detector) following intranasal inoculation of mice. HSV-1 strain KH6 infection was further transmitted to the accessory olfactory bulb (first relay), the medial amygdala (second relay), and the bed nucleus of the stria terminalis and the ventromedial hypothalamus (third relay). HSV-1 strain KH6 also targeted the olfactory and trigeminal systems. HSV-2 strain 186 predominantly attacked the brainstem including the trigeminal system. While both viruses did not induce apoptosis in infected chemosensory neurons, they did in infected brain tissue. These results suggest that neurotropic viruses can invade the brain by infecting vomeronasal chemosensory neurons and that the restrained induction of apoptosis in the infected neurons may facilitate viral transmission to the CNS.     

Quantitative Analysis of Mycobacterial and Propionibacterial DNA in Lymph Nodes of Japanese and European Patients with Sarcoidosis

The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.     

Hyperbaric exposure with high oxygen concentration enhances oxidative capacity of neuromuscular units

The effects of hyperbaric exposure with high oxygen concentration on spinal motoneurons and the skeletal muscle fibers that they innervate were investigated. Five-week-old male rats were exposed to a hyperbaric (1.25 atmospheric pressure) environment with a high oxygen concentration (35.0%) for 6h daily. The number, cell body size, and oxidative enzyme activity of motoneurons innervating the soleus and plantaris muscles were examined after 8 weeks of hyperbaric exposure. In addition, the fiber type distribution, cell size, and oxidative enzyme activity of the slow soleus and fast plantaris muscles were examined. The oxidative enzyme activity of alpha motoneurons innervating the soleus and plantaris muscles increased after hyperbaric exposure, irrespective of their cell body sizes. The percentage of high-oxidative fibers in the soleus and plantaris muscles increased after hyperbaric exposure. The oxidative enzyme activity of all types of fibers in the soleus and plantaris muscles increased after hyperbaric exposure. It is concluded that hyperbaric exposure with high oxygen concentration enhances the oxidative capacity of neuromuscular units.     

Confocal observation of senile plaques in Alzheimer's disease: Senile plaque morphology and relationship between senile plaques and astrocytes

Senile plaques In the brains of Alzheimer's disease (AD) were examined by confocal laser scanning microscopy (CLSM) with the following three findings. First, in sections stained with Congo red, the serial CLSM images of optical sections clearly revealed that a classic plaque is composed of a plaque core and a corona. Radially arranged process-like structures, corresponding to bundles of amyloid fibrils, formed amyloid cores and stronger signals were detected in the center of some cores. Second, in sections stained with Congo red and anti-gllal fibrillary acidic protein (GFAP), reactive astrocytes were found around the senile plaques and many astrocytlc processes surrounded the plaque cores and some processes had penetrated into them. Third, three-dimensional reconstruction on classic plaque revealed that the surface of classic plaque showed a 'coral-like' appearance.     

Invasive fungal infection following reduced-intensity cord blood transplantation for adult patients with hematologic diseases.

Invasive fungal infection (IFI) is a significant complication after allogeneic hematopoietic stem cell transplantation (HSCT); however, we have little information on its clinical features after reduced intensity cord blood transplantation (RICBT) for adults. We reviewed medical records of 128 patients who underwent RICBT at Toranomon Hospital between March 2002 and November 2005. Most of the patients received purine-analogbased preparative regimens. Graft-versus-host disease (GVHD) prophylaxis was a continuous infusion of either tacrolimus 0.03 mg/kg or cyclosporine 3 mg/kg. IFI was diagnosed according to the established EORTC/NIH-MSG criteria. IFI was diagnosed in 14 patients. Thirteen of the 14 had probable invasive pulmonary aspergillosis and the other had fungemia resulting from Trichosporon spp. Median onset of IFI was day 20 (range: 1-82), and no patients developed IFI after day 100. Three-year cumulative incidence of IA was 10.2%. Four of the 13 patients with invasive aspergillosis (IA) developed grade II-IV acute GVHD, and their IA was diagnosed before the onset of acute GVHD. The mortality rate of IFI was 86%. Multivariate analysis revealed that the use of prednisolone >0.2 mg/kg (relative risk 7.97, 95% confidence interval 2.24-28.4, P = .0014) was a significant risk factor for IA. This study suggests that IFI is an important cause of deaths after RICBT, and effective strategies are warranted to prevent IFI.