A neurolinguistic study of autistic children employing dichotic listening

A neurolinguistic study of 20 high functioning right-handed autistic children (19 males and 1 female) was carried out using a dichotic listening test of two-syllabic meaningful words with which to detect the level of binaural separation ability and the condition of hemispheric lateralization of language by examining the degree of ear advantage. The autistic children ranged from 5 to 15 years in age. Their IQ ranged from mildly retarded to normal. (The mean IQ was 67.6 and the mean mental age was 5 yr. 9 mo.). We compared them with non-autistic mentally retarded and normal children as controls, being matched by mental age and right handedness. The autistic children were found to be significantly lower on the level of binaural separation ability than the controls and to have a clearly higher incidence of a left ear advantage than the controls. The autistic and mentally retarded children showed lower advantage than normal children. These results indicate that the autistic children have a dysfunction or immaturity of the central auditory nervous system and an abnormality in the process of hemispheric lateralization of language.     

Relationship between the duration of treatment and the incidence of renal cell tumors in male F344 rats administered potassium bromate

In order to ascertain the minimum induction time, minimum treatment period and total dose required for development of renal cell tumors, KBrO3 at a concentration of 500 ppm was administered in the drinking water to a total of 232 male F344 rats divided into 14 experimental groups and the development of tumors was examined by two different approaches. In a continued-treatment study, administration of KBrO3 was stopped at week 13, 26, 39, 52 or 104 and rats were immediately sacrificed for comparison with controls given distilled water (DW) alone. Renal cell adenomas were found as early as after 26 weeks of treatment with KBrO3. The yields of dysplastic foci, adenomas and adenocarcinomas of the kidney, follicular cell tumors of the thyroid and mesotheliomas of the peritoneum increased with treatment, the final incidences all being statistically significant after administration of KBrO3 for 104 weeks. To examine the effect of discontinued treatment, on the other hand, the rats were given KBrO3 for the first 13, 26, 39 or 52 weeks and were subsequently maintained on DW alone until sacrifice at week 104. The incidences of tumors in these groups were compared with that of a group continuously administered KBrO3 for 104 weeks. The yields of renal dysplastic foci, adenomas and adenocarcinomas in all discontinued-treatment groups were approximately equal to or even higher than those in the group given KBrO3 continuously for 104 weeks. It is concluded that, under the conditions of this study: the minimum induction time for the development of renal adenomas was 26 weeks and the minimum treatment period and total dose for the induction of renal adenomas and adenocarcinomas were 13 weeks and 4 g/kg, respectively, when the rats were maintained thereafter on DW for 2 years.     

DNA vaccine-encapsulated virus-like particles derived from an orally transmissible virus stimulate mucosal and systemic immune responses by oral administration

Delivery of foreign genes to the digestive tract mucosa by oral administration of nonreplicating gene transfer vectors would be a very useful method for vaccination and gene therapy. However, there have been few reports on suitable vectors. In the present study, we found that plasmid DNA can be packaged in vitro into a virus-like particle (VLP) composed of open reading frame 2 of hepatitis E virus, which is an orally transmissible virus, and that these VLPs can deliver this foreign DNA to the intestinal mucosa in vivo. The delivery of plasmid DNA to the mucosa of the small intestine was confirmed by the results of immunohistochemical analyses using an expression plasmid encoding human immunodeficiency virus env (HIV env) gp120. After oral administration of VLPs loaded with HIV env cDNA, significant levels of specific IgG and IgA to HIV env in fecal extracts and sera were found. Moreover, mice used in this study exhibited cytotoxic T-lymphocyte responses specific to HIV env in the spleen, Payer's patches and mesenteric lymph nodes. These findings suggest that VLPs derived from orally transmissible viruses can be used as vectors for delivery of genes to mucosal tissue by oral administration for the purpose of DNA vaccination and gene therapy.     

Doppler tissue analysis of atrial electromechanical coupling in paroxysmal atrial fibrillation.

The aim of this study was to: (1) evaluate atrial electromechanical coupling using M-mode Doppler tissue; and (2) test its clinical impact for detecting atrial abnormalities in paroxysmal atrial fibrillation (AF). Using Doppler tissue, the time intervals from the onset of P wave until the backward motions of the right and left atrioventricular rings in the apical 4-chamber view corresponding to the atrial contractions were measured. In paroxysmal AF group, these intervals were significantly longer than in the control group. Using the criteria that an abnormal time interval from the onset of P wave until the backward motion of the left atrioventricular ring is longer than 112 milliseconds, the sensitivity, the specificity, and the positive predictive values for paroxysmal AF are 73%, 93%, and 93%, respectively. This parameter is affected in patients with paroxysmal AF and should be useful for detecting atrial impairment related to paroxysmal AF.     

Multimers and adiponectin gene 276G>T polymorphism in the Japanese population residing in rural areas.

BACKGROUND: Although it has been shown that high-molecular weight adiponectin is an active form, few studies have attempted to clarify the relationship between high molecular weight adiponectin and markers linked with cardiovascular diseases in the general population. METHODS: We screened 236 Japanese study participants recruited from the general population, residing in one large and four small islands. In addition to serum lipids and lipoproteins, serum total adiponectin and each multimer were measured. The genotype single-nucleotide polymorphism 276G>T was detected in real-time PCR with LightCycler hybridization probes, using fluorescent-labeled nucleotides. RESULTS: Multiple linear regression analysis showed that high-molecular weight adiponectin, as well as total adiponectin, were significantly correlated with body weight, body mass index, high-density lipoprotein cholesterol and triglycerides. Total adiponectin and high-molecular weight adiponectin concentrations were not significantly different between GG and TX (GT and TT) genotypes of 276G>T polymorphism in the adiponectin gene. Interestingly, no differences were observed for participants from the large island between GG and TX genotypes with regard to both total adiponectin and high-molecular weight adiponectin, whereas significant differences were observed for those from the small islands. CONCLUSIONS: Our results show that total adiponectin and high-molecular weight adiponectin are associated with similar factors in the general population. Furthermore, different effects of 276G>T for participants from small and large islands suggest that regional background due to geographic barriers may control the effects of 276G>T on adiponectin concentrations.     

Surgical tissue handling methods to optimize ex vivo fluorescence with the activatable optical probe γ‐glutamyl hydroxymethyl rhodamine green

Optical fluorescence imaging has been developed as an aid to intraoperative diagnosis to improve surgical and endoscopic procedures. Compared with other intraoperative imaging methods, it is lower in cost, has a high safety margin, is portable and easy to use. γ‐glutamyl hydroxymethyl rhodamine green (gGlu‐HMRG) is a recently developed activatable fluorescence probe that emits strong fluorescence in the presence of the enzyme γ‐glutamyl transpeptidase (GGT), which is overexpressed in many cancers, including ovarian cancer. Ex vivo testing is important for clinical approval of such probes. The diagnostic performance of gGlu‐HMRG in fresh excised surgical specimens has been reported; however, details of tissue handling have not been optimized. In this study, we investigated four different tissue handling procedures to optimize imaging in excised tumor specimens. The fluorescence intensity time courses after the different tissue handling methods were compared. Additionally, the fluorescence positive areas were correlated with the presence of red fluorescent protein (RFP) in an RFP positive cell line as the standard of reference for cancer location. In the ‘intact’ groups, tumors yielded quick and homogeneous activation of gGlu‐HMRG. In the ‘rinse’ and ‘cut’ groups, the fluorescence intensity of the tumor was a little lower than that in the intact group. In the ‘pressed’ groups, however, fluorescence intensity from gGlu‐HMRG was lower over the entire time course, suggesting a decrease or relocation of excreted GGT. In conclusion, we demonstrate that the method of tissue handling prior to ex vivo imaging with the activatable probe gGlu‐HMRG has a strong influence on the signal derived from the specimen. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.     

Accurate and simple method for quantification of hepatic fat content using magnetic resonance imaging: a prospective study in biopsy-proven nonalcoholic fatty liver disease

Background

To assess the degree of hepatic fat content, simple and noninvasive methods with high objectivity and reproducibility are required. Magnetic resonance imaging (MRI) is one such candidate, although its accuracy remains unclear. We aimed to validate an MRI method for quantifying hepatic fat content by calibrating MRI reading with a phantom and comparing MRI measurements in human subjects with estimates of liver fat content in liver biopsy specimens.

Methods

The MRI method was performed by a combination of MRI calibration using a phantom and double-echo chemical shift gradient-echo sequence (double-echo fast low-angle shot sequence) that has been widely used on a 1.5-T scanner. Liver fat content in patients with nonalcoholic fatty liver disease (NAFLD, n = 26) was derived from a calibration curve generated by scanning the phantom. Liver fat was also estimated by optical image analysis. The correlation between the MRI measurements and liver histology findings was examined prospectively.

Results

Magnetic resonance imaging measurements showed a strong correlation with liver fat content estimated from the results of light microscopic examination (correlation coefficient 0.91, P < 0.001) regardless of the degree of hepatic steatosis. Moreover, the severity of lobular inflammation or fibrosis did not influence the MRI measurements.

Conclusions

This MRI method is simple and noninvasive, has excellent ability to quantify hepatic fat content even in NAFLD patients with mild steatosis or advanced fibrosis, and can be performed easily without special devices.     

Plaque formation assay for human parainfluenza virus type 1

Human parainfluenza virus type 1 (hPIV1) generally does not show visible plaques in common cell lines, including Lewis lung carcinoma-monkey kidney (LLC-MK(2)) cells, by plaque formation assays for human parainfluenza virus type 3 (hPIV3) and Sendai virus. In several conditions of the plaque formation assay, complete elimination of serum proteins in the overlay medium was necessary for visualization of hPIV1-induced plaque formation in LLC-MK(2) cells. We developed a plaque formation assay for hPIV1 isolation and titration in LLC-MK(2) cells using an initial overlay medium of bovine serum albumin-free Eagle's minimum essential medium containing agarose and acetylated trypsin for 4-6 d followed by a second overlay staining medium containing agarose and neutral red. The assay allowed both laboratory and clinical hPIV1 strains to form large plaques. The plaque reduction assay was also performed with rabbit anti-hPIV1 antibody as a general evaluation model of viral inhibitors to decrease both the plaque number and size. The results indicate that the plaque formation assay is useful for hPIV1 isolation, titration, evaluation of antiviral reagents and epidemiologic research.