Effect of age on the fractional anisotropy (FA) value of peripheral nerves and clinical significance of the age-corrected FA value for evaluating polyneuropathies

Introduction

We investigated the correlation between age and the fractional anisotropy (FA) values of peripheral nerves in healthy adults and compared the age-corrected FA values of peripheral nerves in healthy subjects and patients with polyneuropathy.

Methods

The institutional review board approved this study and informed consent was obtained from all participants before entry into the study. We optimized diffusion tensor imaging using a 3-T magnetic resonance scanner and an extremity coil for scanning tibial nerves. The effect of age and sex on the FA values of tibial nerves in healthy volunteers was investigated and the age-corrected FA values of tibial nerves in healthy volunteers and patients with polyneuropathy were compared.

Results

The maximum FA values of the tibial nerves remained constant until age 45 (approximately 0.516); they subsequently decreased by 0.004/year in healthy volunteers. After removing the effect of age with an age-adjusted equation, the median maximum FA values in the volunteers and patients were 0.518 (range, 0.406–0.616) and 0.442 (range, 0.376–0.530), respectively. The age-corrected FA values were significantly lower in the patients than the healthy volunteers (p?p?=?0.416).

Conclusion

The age-corrected FA value of the peripheral nerves helps to differentiate between age-related peripheral nerve degeneration and polyneuropathies.     

Comparison of moxifloxacin and levofloxacin in an epithelial disorder model using cultured rabbit corneal epithelial cell sheets

Background

When ophthalmic drug solutions are developed and clinically applied, their influence on corneal epithelium is an important issue. In the past, cells obtained by monolayer culture in vitro were used for evaluation of such influence. We recently created an experimental model of cell damage repair closer to the live body than conventional models by using layered sheets of cultured corneal epithelium. The present study was undertaken to evaluate the influence of ophthalmic moxifloxacin hydrochloride (MFLX) solution in comparison to that of ophthalmic levofloxacin (LVFX) solution using this model.

Methods

Corneal epithelium cells were collected from corneal tissue specimens of white rabbits and subjected to air-lift culture to induce layering. Epithelial cell defects were created by a sponge soaked in 1?N aqueous sodium hydroxide. After removal of the sponge, either ophthalmic MFLX solution or ophthalmic LVFX solution was dropped onto the specimens three times daily (washed 1?min after each dose, followed by continuation of air-lifting culture). The percentage of the defective area repaired (percent defect repair) was evaluated. Each of the ophthalmic MFLX solution and the ophthalmic LVFX solution was used after the stock solution was diluted fourfold (1:4). Drug-free culture medium served as the negative control. Benzalconium chloride solution (BAC) 0.01% served as the positive control.

Results

In the negative control group, complete repair of the defect with epithelial cells was seen 4?days after the start of treatment. In the positive control group, repair was suppressed. In the MFLX group and the LVFX group, the defect was repaired at each drug concentration, showing no significant difference from the negative control group. Thus, in this study using layered sheets of cultured corneal epithelium (a model closer to the living body than conventional models), the corneal epithelial defect was repaired in the ophthalmic MFLX solution treatment group and the ophthalmic LVFX solution treatment group to a degree similar to that in the negative control group.

Conclusions

These results suggest that neither MLFX nor LVFX suppresses repair of corneal epithelial damage.     

A novel combined adjuvant for nasal delivery elicits mucosal immunity to influenza in aging

Since a combination of flt3 ligand plasmid (pFL) and CpG-oligodeoxynucleotides (ODN)³ as a dendritic cell (DC)-targeting double mucosal adjuvant elicited ovalbumin-specific secretory IgA (S-IgA) antibody (Ab) responses, we examined whether this double adjuvant could induce influenza-specific protective immunity in aged mice. A double adjuvant plus A/Puerto Rico/8/34 (PR8) hemagglutinin (HA) induced increased numbers of CD11b⁺ CD11c⁺ DCs and both CD4⁺ Th1- and Th2-type responses in the nasopharyngeal-associated lymphoreticular tissue, nasal passages and cervical lymph nodes. Further, increased levels of PR8 HA-specific S-IgA Ab responses were detected in the upper respiratory tact (URT) of aged and young adult mice given nasal PR8 HA with this double adjuvant. Thus, when mice were challenged with PR8 virus via the nasal route, both aged and young adult mice given nasal vaccine exhibited complete protection. Further, IgA-deficient mice nasally immunized with a double adjuvant influenza vaccine failed to provide protection against PR8 challenge. These results indicate that a nasal double adjuvant successfully induces PR8 HA-specific IgA Ab responses in both young adult and aged mice, which are essential for the prevention of influenza infection in the murine URT.     

Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes

Among acquired stem cell disorders, pathological links between myelodysplastic syndromes (MDS) and aplastic anaemia (AA), and paroxysmal nocturnal haemoglobinuria (PNH) and AA, have been often described, whereas the relationship between MDS and PNH is still unclear. We analysed blood cells of patients with MDS to determine the incidence of the PNH clone, and analysed the PIG-A gene to find mutations characteristic of the PNH clone in MDS. In four (10%) of 40 patients with MDS, flow cytometry showed affected erythrocytes and granulocytes negative for decay-accelerating factor (DAF) and CD59. The population of affected erythrocytes was smaller in MDS patients with PNH clone (MDS/PNH) than in patients with de novo PNH, and haemolysis was milder in the MDS/PNH patients. PIG-A mutations were found in granulocytes of all patients with MDS/PNH. In type and site, the PIG-A mutations were heterogenous, similar to that observed in de novo PNH; i.e. no mutation specific to MDS/PNH was identified. Of note, three of four patients with MDS/PNH each had two PNH clones with different PIG-A mutations, suggesting that PIG-A is mutable in patients with MDS/PNH. In a MDS/PNH patient with trisomy 8, FISH detected a distinct karyotype in a portion of granulocytes with PNH phenotype, indicating that PNH and MDS partly shared affected cells. Thus, MDS predisposes to PNH by creating conditions favourable to the genesis of PNH clone. Considering the increasing prevalence and incidence of MDS, these disorders could be useful for investigating the mechanism by which PIG-A mutation is induced.     

Significance of serum enzyme changes after cardiac catheterization and selective coronary arteriography.

The serum creatine kinase (CK), aspartate transaminase (AST), lactic dehydrogenase (LD) and alpha-hydroxybutyric dehydrogenase (HBD) were determined before and 3, 6, 18, and 36 hours after cardiac catheterization and angiocardiography in 56 consecutive patients with ischaemic heart disease. Five of these patients whose serum enzyme levels were higher than normal before the procedure were excluded from the study. Forty-one of the remaining 51 patients had left ventriculography and also selective coronary arteriography. In these 41 patients (groups 1 and 2--see below), the mean serum CK levels increased after the procedure to exceed the upper limit of normal at every study interval. The mean serum AST, LD, and HBD levels generally remained within the normal range at all study intervals, though serum AST increased abnormally in 9 of the 41 patients (22%) and serum LD and HBD each increased above the normal limit in 2 of 41 patients (4.9%). In 24 patients (group 1) whose coronary arteriograms showed insignificant coronary narrowing (less than 75%) in any of the three major coronary arteries, the increase in serum CK was significantly higher than in 17 patients (group 2) with greater than 75% narrowings in at least one of the three major coronary arteries. However, the degree of serum CK elevation observed during the postangiographic period was much lower than that in another group of 30 consecutive patients with acute myocardial infarction. In 10 patients (group 3) who had the same procedure as groups 1 and 2 except without the selective coronary arteriography, the serum enzyme levels showed no noticeable increase after the procedure. The difference in postangiographic serum CK elevation between patients with and without selective coronary arteriography and the difference between group 1 (without significant coronory narrowing) and group 2 (with significant narrowing) strongly suggest that the raised serum CK levels represent some form of myocardial damage caused by the coronary arteriography, which, however, is different at least in degree from that of acute myocardial infarction.     

An assessment of dobutamine echocardiography and end-diastolic wall thickness for predicting post-revascularization functional recovery in patients with chronic coronary artery disease

AIMS: This study investigated the functional outcome of wall-thinned,akinetic myocardium after revascularization and evaluated theaccuracy of dobutamine echocardiography in predicting post-revascularizationfunctional recovery with the assessment of end-diastolic wallthickness in chronic ischaemic patients. METHODS AND RESULTS: Fifty-three patients underwent dobutamine echocardiography beforecoronary revascularization. End-diastolic wall thickness wasalso evaluated before and after revascularization. The sensitivityand specificity of dobutamine echocardiography to predict post-revascularizationfunctional recovery were 69% and 100% in 58 akinetic/dyskineticsegments, and 86% and 57% in 96 hypokinetic segments. Of 19akinetic/dyskinetic segments with a preserved end-diastolicwall thickness, 17 (89%) showed functional recovery after revascularization,and dobutamine detected 14 (83%) of these 17 segments. Of 39akinetic/dyskinetic segments with a thinned end-diastolic wallthickness, 15 (38%) achieved functional recovery, whereas dobutamineechocardiography detected recovery in only eight (53%). Further,of these 15 viable, wall-thinned segments, 12 (80%) showed anincreased end-diastolic wall thickness after revascularization(mean±SD were from 5·6±0·7 mm atbaseline to 7·4±1·3 mm and 9·7±1mm after 1 week and after 3 months, respectively), and only5 (42%) of these responded to dobutamine. CONCLUSION: Dobutamine echocardiography showed a lessened sensitivity topredict post-revascularization functional recovery in akinetic/dyskineticsegments with a thinned end-diastolic wall thickness that subsequentlyincreased in size.     

Development of sensitivity to maturation-inducing steroids in the oocytes of the daily spawning teleost, the kisu Sillago japonica

The responsiveness of oocytes to 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-diOH-P), 17 alpha-hydroxyprogesterone (17 alpha-OH-P), and silver carp gonadotropin (GtH) was examined in vitro at seven different times of the day (0100, 0500, 0800, 1000, 1300, 1700, 2100 hr) in a daily spawning teleost, the kisu Sillago japonica. 17 alpha,20 beta-DiOH-P, 17 alpha-OH-P, and GtH were effective in inducing germinal vesicle breakdown (GVBD) and ovulation in kisu oocytes. However, the oocytes of the kisu responded to these hormones during a limited time of the day (2100-1000 hr), and their responsiveness to steroids and GtH was different with the sampling time. After a 20-hr incubation, the oocytes with yolk globules were classified into four stages based on their responses (GVBD) to GtH and steroids. Stage A, the oocytes did not respond to either GtH or steroids. These unresponsive oocytes were observed in all the ovaries examined. Stage B, GVBD could be induced by GtH but not by steroids. These oocytes were found in the ovaries collected from 2100 to 1000 hr. Stage C, GVBD could be induced by both GtH and steroids. These oocytes were found only between 0800 and 1000 hr. Stage D, oocytes spontaneously underwent GVBD without hormones. These oocytes were found between 1300 and 1700 hr. Ovulated oocytes were found in the ovaries collected during 1700-0500 hr. These results indicate that the kisu possesses a daily rhythm in oocyte development from stage A to stage D, and that the sensitivity to 17 alpha,20 beta-diOH-P appears at stage C.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronically persistent infection with human cytomegalovirus in human lymphoblasts.

Cells from a line of human lymphocytes originating from a leukemic patient were persistently infected with human cytomegalovirus. Assays of infectious centers and fluorescent antigen staining indicated that 1%--10% of the cells were infected. It appears that persistent infection is due to an equilibrium between the release of virus by infected host cells and the growth of uninfected cells rather than to defective virus or temperature-sensitive mutants.