Diffuse optical tomography using multi-directional sources and detectors

Diffuse optical tomography (DOT) is an advanced imaging method used to visualize the internal state of biological tissues as 3D images. However, current continuous-wave DOT requires high-density probe arrays for measurement (less than 15-mm interval) to gather enough information for 3D image reconstruction, which makes the experiment time-consuming. In this paper, we propose a novel DOT measurement system using multi-directional light sources and multi-directional photodetectors instead of high-density probe arrays. We evaluated this system’s multi-directional DOT through computer simulation and a phantom experiment. From the results, we achieved DOT with less than 5-mm localization error up to a 15-mm depth with low-density probe arrays (30-mm interval), indicating that the multi-directional measurement approach allows DOT without requiring high-density measurement.OCIS codes: (100.3010) Image reconstruction techniques, (110.0113) Imaging through turbid media, (170.3880) Medical and biological imaging     

Mesenchymal stem cells that produce neurotrophic factors reduce ischemic damage in the rat middle cerebral artery occlusion model.

Mesenchymal stem cells (MSC) were reported to ameliorate functional deficits after stroke in rats, with some of this improvement possibly resulting from the action of cytokines secreted by these cells. To enhance such cytokine effects, we previously transfected the telomerized human MSC with the BDNF gene using a fiber-mutant adenovirus vector and reported that such treatment contributed to improved ischemic recovery in a rat transient middle cerebral artery occlusion (MCAO) model. In the present study, we investigated whether other cytokines in addition to BDNF, i.e., GDNF, CNTF, or NT3, might have a similar or greater effect in this model. Rats that received MSC-BDNF (P < 0.05) or MSC-GDNF (P < 0.05) showed significantly more functional recovery as demonstrated by improved behavioral test results and reduced ischemic damage on MRI than did control rats 7 and 14 days following MCAO. On the other hand, rats that received MSC-CNTF or MSC-NT3 showed neither functional recovery nor ischemic damage reduction compared to control rats. Thus, MSC transfected with the BDNF or GDNF gene resulted in improved function and reduced ischemic damage in a rat model of MCAO. These data suggest that gene-modified cell therapy may be a useful approach for the treatment of stroke.     

Plasma concentration of brain natriuretic peptide as a biochemical marker for the evaluation of right ventricular overload and mortality in chronic respiratory disease

The purpose of this study was to evaluate whether the plasma brain natriuretic peptide (BNP) concentration is a useful marker of right ventricular (RV) overload and whether it has prognostic value as a predictor of death in patients with chronic respiratory disease (CRD). We measured the plasma BNP and atrial natriuretic peptide (ANP) concentrations in 31 consecutive patients with CRD who underwent right-heart catheterization to evaluate pulmonary hypertension. All patients were followed for >12 months. The plasma BNP concentration closely correlated with the mean pulmonary artery pressure and pulmonary vascular resistance (r=0.62, P<0.0005 and r=0. 85, P<0.0001), and showed a weak linear correlation with cardiac output (r=-0.36, P<0.05). During the follow-up period, 5 (16%) end-stage CRD deaths (4 RV heart failure and 1 respiratory infection) and 2 non-end-stage CRD deaths occurred. In a stepwise multivariate Cox proportional-hazards regression analysis including age, sex, BNP, ANP, hemodynamic variables and the ratio of PaO(2) to fraction of inspired oxygen, only BNP (P<0.05) was an independent predictor of end-stage CRD death. The upward and leftward shift in the receiver operating characteristic curve between patients with end-stage CRD death and those without was greater for BNP than for ANP. Our findings suggest that the plasma BNP concentration may be an inexpensive, simple and useful marker of RV overload and end-stage CRD death in CRD patients. These preliminary results need to be confirmed in a large series of CRD patients.     

An Alternative Approach to Atopic Dermatitis: Part I-Case-Series Presentation

Atopic dermatitis (AD) is a complex disease of obscure pathogenesis.A substantial portion of AD patients treated with conventionaltherapy become intractable after several cycles of recurrence.Over the last 20 years we have developed an alternative approachto treat many of these patients by diet and Kampo herbal medicine.However, as our approach is highly individualized and the Kampoformulae sometimes complicated, it is not easy to provide evidenceto establish usefulness of this approach. In this Review, todemonstrate the effectiveness of the method of individualizedKampo therapy, results are presented for a series of patientswho had failed with conventional therapy but were treated afterwardsin our institution. Based on these data, we contend that thereexist a definite subgroup of AD patients in whom conventionaltherapy fails, but the ‘Diet and Kampo’ approachsucceeds, to heal. Therefore, this approach should be consideredseriously as a second-line treatment for AD patients. In theDiscussion, we review the evidential status of the current conventionalstrategies for AD treatment in general, and then specificallydiscuss the possibility of integrating Kampo regimens into it,taking our case-series presented here as evidential basis. Weemphasize that Kampo therapy for AD is more ‘art’than technology, for which expertise is an essential pre-requisite.     

Rapid pulsed-field gel electrophoresis technique for determination of genetic diversity of <Emphasis Type="Italic">Serratia marcescens</Emphasis>

 Seventeen Serratia marcescens strains were isolated from patients admitted to a hospital in the Tokyo metropolitan area. In order to study their genetic diversity, pulsed-field gel electrophoresis (PFGE) was performed. Clear bands were not observed by the standard PFGE technique following the instruction manual from the company. To obtain clear results, it was necessary to include some additional steps to the preparation of PFGE samples. We added an inactivation step for DNase using formaldehyde, and the bacterial strains were embedded in thinner plug molds than usual. These modifications were effective with all strains, and the complete PFGE pattern was obtained in the samples treated with formaldehyde and using thin plug molds. We established a rapid method to obtain a high-quality PFGE result for S. marcescens. Received: March 19, 2002 / Accepted: July 10, 2002     

Organic-inorganic hybrid-nanocarrier of siRNA constructing through the self-assembly of calcium phosphate and PEG-based block aniomer.

The development of siRNA delivery systems is a major key for practical RNA therapy that holds promise for the treatment of life-threatening human diseases, yet there still exists significant difficulties in their construction because of the various requirements including high transfection efficacy, tolerability in the biological medium, and low toxicity. Here we report the novel preparation route of organic-inorganic hybrid-nanocarriers entrapping siRNA based on the self-assembly of the block aniomer, poly(ethylene glycol)-block-poly(methacrylic acid), with calcium phosphate crystals. The nanocarriers have diameters in the range of several hundreds of nanometers and revealed excellent colloidal stability due to the steric stabilization effect of the PEG palisade. The biological activity of siRNA loaded in nanocarriers was assessed using 293 cells stably expressing luciferase gene, showing the remarkably high gene silencing-efficacy without the use of any adjuvant molecules such as chroloquin. Further advantage of the system is the serum tolerability, which is of a critical issue in in vivo application.     

Social adaptation of children with congenital fecal dysfunction: from the viewpoint of the mother-child relationship

Excretory dysfunction associated with congenital anal anomalies (a generic term that includes anal atresia and Hirschsprung's disease) is presumed to greatly affect the psychology of the affected children. In this study, we conducted a survey on the psychological status of children with excretory dysfunction, and investigated the relationship between the affected children and their families in addition to their social life. Four children with fecal dysfunction due to a congenital anal anomaly and their mothers were interviewed. The results of psychological tests in the children and mothers along with our findings in the interviews with the children and mothers, were included in the data analysis. We found that regardless of the degree of excretory dysfunction, the child's state of mind was influenced by whether the mother exhibited warmth or criticism towards her child and whether there was a support system for the mother and child. We suggest that psychiatric consultation is necessary for these children.     

Staphylococcal lipoteichoic acid inhibits delayed-type hypersensitivity reactions via the platelet-activating factor receptor

Staphylococcus aureus infections are known triggers for skin inflammation and can modulate immune responses. The present studies used model systems consisting of platelet-activating factor receptor-positive and -negative (PAF-R-positive and -negative) cells and PAF-R-deficient mice to demonstrate that staphylococcal lipoteichoic acid (LTA), a constituent of Gram-positive bacteria cell walls, acts as a PAF-R agonist. We show that LTA stimulates an immediate intracellular Ca2+ flux only in PAF-R-positive cells. Intradermal injections of LTA and the PAF-R agonist 1-hexadecyl-2-N-methylcarbamoyl glycerophosphocholine (CPAF) induced cutaneous inflammation in wild-type but not PAF-R-deficient mice. Systemic exposure to LTA or CPAF inhibited delayed-type hypersensitivity (DTH) reactions to the chemical dinitrofluorobenzene only in PAF-R-expressing mice. The inhibition of DTH reactions was abrogated by the addition of neutralizing antibodies to IL-10. Finally, we measured levels of LTA that were adequate to stimulate PAF-R in vitro on the skin of subjects with infected atopic dermatitis. Based on these studies, we propose that LTA exerts immunomodulatory effects via the PAF-R through production of the Th2 cytokine IL-10. These findings show a novel mechanism by which staphylococcal infections can inhibit Th1 reactions and thus worsen Th2 skin diseases, such as atopic dermatitis.     

Low incidence of vascular complications in patients with diabetes mellitus associated with liver cirrhosis as compared with type 2 diabetes mellitus

We compared clinical features and vascular complications of patients with diabetes mellitus associated with liver cirrhosis versus patients with type 2 diabetes mellitus. Subjects were 19 patients (LC-DM group) in whom diabetes was diagnosed after development of liver cirrhosis. Control consisted of 38 patients with type 2 diabetes (T2DM group) matched for sex, age, duration of diabetes, body mass index, treatment, and degree of glycemic control, which was determined by glycoalbumin. The LC-DM group had significantly more smokers, higher serum insulin levels, more insulin resistance calculated by homeostasis model assessment, lower blood counts (white and red blood cells, hemoglobin, and platelets), and lower serum levels of total cholesterol, triglyceride, low density lipoprotein cholesterol and lipoprotein (Lp)(a) than the T2DM group. The incidence of diabetic retinopathy and cerebrovascular disease was significantly lower in the LC-DM group compared to the T2DM group. Logistic regression analysis indicated that Lp(a) and the diabetes duration were significant predictors for the retinopathy, while Lp(a) was a significant predictor for the cerebrovascular complication. In diabetes associated with liver cirrhosis, the incidence of diabetic retinopathy and cerebrovascular disease is lower than in type 2 diabetes mellitus in this study, probably because of lower levels of serum Lp(a).