Analyses of very early hemopoietic regeneration after bone marrow transplantation: comparison of intravenous and intrabone marrow routes

In bone marrow transplantation (BMT), bone marrow cells (BMCs) have traditionally been injected intravenously. However, remarkable advantages of BMT via the intra-bone-marrow (IBM) route (IBM-BMT) over the intravenous route (IV-BMT) have been recently documented by several laboratories. To clarify the mechanisms underlying these advantages, we analyzed the kinetics of hemopoietic regeneration after IBM-BMT or IV-BMT in normal strains of mice. At the site of the direct injection of BMCs, significantly higher numbers of donor-derived cells in total and of c-kit(+) cells were observed at 2 through 6 days after IBM-BMT. In parallel, significantly higher numbers of colony-forming units in spleen were obtained from the site of BMC injection. During this early period, higher accumulations of both hemopoietic cells and stromal cells were observed at the site of BMC injection by the IBM-BMT route. The production of chemotactic factors, which can promote the migration of a BM stromal cell line, was observed in BMCs obtained from irradiated mice as early as 4 hours after irradiation, and the production lasted for at least 4 days. In contrast, sera collected from the irradiated mice showed no chemotactic activity, indicating that donor BM stromal cells that entered systemic circulation cannot home effectively into recipient bone cavity. These results strongly suggest that the concomitant regeneration of microenvironmental and hemopoietic compartments in the marrow (direct interaction between them at the site of injection) contributes to the advantages of IBM-BMT over IV-BMT. Disclosure of potential conflicts of interest is found at the end of this article.     

Improving effects of the mushroom Yamabushitake (Hericium erinaceus) on mild cognitive impairment: a double-blind placebo-controlled clinical trial

A double-blind, parallel-group, placebo-controlled trial was performed on 50- to 80-year-old Japanese men and women diagnosed with mild cognitive impairment in order to examine the efficacy of oral administration of Yamabushitake (Hericium erinaceus), an edible mushroom, for improving cognitive impairment, using a cognitive function scale based on the Revised Hasegawa Dementia Scale (HDS-R). After 2 weeks of preliminary examination, 30 subjects were randomized into two 15-person groups, one of which was given Yamabushitake and the other given a placebo. The subjects of the Yamabushitake group took four 250 mg tablets containing 96% of Yamabushitake dry powder three times a day for 16 weeks. After termination of the intake, the subjects were observed for the next 4 weeks. At weeks 8, 12 and 16 of the trial, the Yamabushitake group showed significantly increased scores on the cognitive function scale compared with the placebo group. The Yamabushitake group's scores increased with the duration of intake, but at week 4 after the termination of the 16 weeks intake, the scores decreased significantly. Laboratory tests showed no adverse effect of Yamabushitake. The results obtained in this study suggest that Yamabushitake is effective in improving mild cognitive impairment.     

Differentiation and mechanisms of prevention and termination of verapamil-sensitive sustained ventricular tachycardia

The purpose of this study was to differentiate by means of electrophysiologic study, a drug's ability to terminate or to prevent ventricular tachycardia (VT). Differences between the 2 effects were examined in patients with VT and the underlying mechanisms were studied in verapamil-responsive idiopathic sustained VT. The clinical significance of the distinction for chronic oral drug therapy is discussed.

Thirty-five cases of inducible sustained VT were studied. A drug was considered “preventative” if it prevented VT induction and repetitive ventricular response, and “terminating” if it stopped induced VT within 15 complexes or could stop VT after its intravenous administration.

Prevention and termination occurred together in 13 of 19 cases (68%) with disopyramide, in 10 of 19 cases (53%) with procainamide, in 8 of 12 cases (67%) with lidocaine, in 11 of 15 cases (73%) with mexiledne, and in 10 of 16 cases (63%) with verapamil. In the 16 in which verapamil terminated VT, VT rate immediately before termination slowed markedly from 167 ± 33 to 134 ± 28 beats/min. In the 6 cases without preventative effects, minimal and maximal premature intervals for VT induction increased significantly, from 291 ± 70 to 335 ± 85 ms and 323 ± 68 to 423 ± 109 ms, respectively, after verapamil administration.

In 2 cases in which verapamil had a terminating effect, 5 mg of verapamil restored sinus rhythm but 10 mg caused premature beats resembling VT complexes. In another 2, 5 mg of verapamil lengthened the minimal premature interval; 10 mg increased both minimal and maximal premature intervals and lengthened the VT cycle.

The chronic oral aukninistration of verapamil resulted in disappearance of VT attacks in 2 of 4 patients and a decrease in both their number and duration in 2 of 4 patients in whom both termination and prevention were seen in the electrophysiologic study. However, in 4 patients who had only termination, the VT episodes remained unchanged in 2 and even increased in the other 2.     

Revised guideline for the diagnosis and treatment of acquired idiopathic generalized anhidrosis in Japan

Acquired idiopathic generalized anhidrosis (AIGA) is characterized by an acquired impairment in total body sweating despite exposure to heat or exercise. Severe cases may result in heatstroke. Most cases of AIGA have been reported in Asia, especially in Japan. However, there is limited information on the epidemiology of this condition, and no diagnostic criteria or appropriate treatment options have been established. This guideline was developed to fill this gap. It contains information on the etiology, diagnosis, evaluation of disease severity and evidence‐based recommendations for the treatment of AIGA. Appropriate treatment according to disease severity may relieve the clinical manifestations and emotional distress experienced by patients with AIGA.     

Diagnosis of nail psoriasis: evaluation of nail-derived microRNAs as potential novel biomarkers

Background

MicroRNA levels in sera or hair may potentially be useful biomarkers for various diseases. The diagnosis of nail diseases is sometimes difficult, and nail psoriasis without skin lesions is indistinguishable from nail changes caused by other diseases.

Objectives

We evaluated nail microRNA levels as biomarkers for the diagnosis of psoriasis patients.

Materials & methods

MicroRNA levels were examined in psoriasis patients with (11 patients) and without (six patients) nail changes. Normal control nails were collected from 17 healthy subjects. Eight patients with other diseases who also had nail changes were also included as disease controls.

Results

Microarray, real-time PCR, and in situ hybridisation indicated that the expression levels of nail miR- 4454 were decreased in psoriasis patients with nail changes, compared to those patients with other diseases involving nail change, or healthy subjects. The miR-4454 levels in nails showed a significant inverse correlation with the Nail Psoriasis Severity Index (NAPSI) score, suggesting that nail miR-4454 levels reflect nail condition.

Conclusion

The levels of microRNAs in nails may be suitable biomarkers for diagnosis or evaluation of disease activity of psoriasis.

     

Relationship between plasma total homocysteine level and dietary caffeine and vitamin B6 intakes in pregnant women

A high total homocysteine (tHcy) level during pregnancy is a risk factor for adverse perinatal outcomes, such as fetal growth restriction and preeclampsia. Caffeine is assumed to increase tHcy levels by acting as a vitamin B₆ antagonist. The objective of this study was to examine a relationship between circulating tHcy levels and dietary caffeine and vitamin B₆ intakes in pregnant Japanese women. A total of 321 healthy women with singleton pregnancies were recruited in metropolitan Tokyo, from June to December 2008, resulting in the final number included in the study as 254. Dietary caffeine intakes did not correlate with plasma tHcy levels. When we analyzed the data according to caffeinated beverages, caffeinated tea consumption was positively associated with plasma tHcy levels only among the women with a high intake of vitamin B₆, after controlling for confounding factors (P = 0.029). No correlation between coffee consumption and plasma tHcy levels was found. Pregnant Japanese women might need to cut down the consumption of caffeinated tea as well as take sufficient vitamin B₆ in order to prevent the tHcy levels from increasing.     

Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan

The spread of antimicrobial-resistant Neisseria gonorrhoeae worldwide is a critical issue in the control of sexually transmitted infections. The purpose of this study was to clarify recent trends in the susceptibility of N. gonorrhoeae to various antimicrobial agents and to compare these data with our previous data. Minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined in N. gonorrhoeae strains clinically isolated from male gonococcal urethritis. In addition, amino acid sequencing of penicillin-binding protein (PBP) 2, encoded by the penA gene, was analyzed so that genetic analysis of mosaic PBP 2 could clarify the susceptibility of the strains to cefixime and other cephalosporins. The susceptibility rate for ceftriaxone, cefodizime, and spectinomycin, agents whose use is recommended by the guideline of the Japanese Society of Sexually Transmitted Infections (JSSTI), was 100 %. The susceptibility rates of the strains to penicillin G and ciprofloxacin were lower than those in previous reports. Mosaic PBP 2 structures were detected in 51.9 % of the strains and the MICs of the strains with the mosaic PBP 2 to cefixime were much higher than those of the strains without the mosaic PBP 2. In the clinical situation, the treatment regimen recommended by the JSSTI remains appropriate; however, the susceptibility to cephalosporins should be intensively surveyed because strains with mosaic PBP 2 were commonly detected.     

Two region‐dependent pathways of eosinophilic neuronal death after transient cerebral ischemia

Various types of eosinophilic neurons (ENs) are found in the post‐ischemic brain. We examined the temporal profile of ENs in the core and peripheral regions of the ischemic cortex, and analyzed the relationship to the expression of various cell death‐related factors. Unilateral forebrain ischemia was induced in Mongolian gerbils by transient common carotid artery occlusions, and the brains from 3 h to 2 weeks post‐ischemia were prepared for morphometric and immunohistochemical analysis of ENs. ENs with minimally abnormal nuclei and swollen cell bodies appeared at 3 h in the ischemic core and at 12 h in the periphery. In both locations multiple cell death‐related factors including calcium, µ‐calpain, cathepsin D, 78 kDa glucose‐regulated protein (GRP78) and ubiquitin were activated. In the ischemic core, pyknosis and irregularly atrophic cytoplasm peaked at 12 h, which was associated with significant increases in staining for calcium and µ‐calpain. ENs with pyknosis and scant cytoplasm peaked at 4 days and were positive for TUNEL and calcium staining. In the ischemic periphery, ENs had slightly atrophic cytoplasm and sequentially developed pyknosis, karyorrhexis and karyolysis over 1 week. These cells were positive for TUNEL and calcium staining. All types of EN were negative for caspase 3. There may be two region‐dependent pathways of EN changes in the post‐ischemic brain: pyknosis with cytoplasmic shrinkage in the core, and nuclear disintegration with slightly atrophic cytoplasm in the periphery. This difference coordinates different activation patterns of cell death‐related factors in ENs.