Regional fractional ventilation mapping in spontaneously breathing mice using hyperpolarized 129Xe MRI

The feasibility of ventilation imaging with hyperpolarized (HP) ¹²⁹Xe MRI has been investigated for quantitative and regional assessment of ventilation in spontaneously breathing mice. The multiple breath ventilation imaging technique was modified to the protocol of spontaneous inhalation of HP ¹²⁹Xe delivered continuously from a ¹²⁹Xe polarizer. A series of ¹²⁹Xe ventilation images was obtained by varying the number of breaths before the ¹²⁹Xe lung imaging. The fractional ventilation, r, was successfully evaluated for spontaneously breathing mice. An attempt was made to detect ventilation dysfunction in the emphysematous mouse lung induced by intratracheal administration of porcine pancreatic elastase (PPE). As a result, the distribution of fractional ventilation could be visualized by the r map. Significant dysfunction of ventilation was quantitatively identified in the PPE‐treated group. The whole‐lung r value of 0.34 ± 0.01 for control mice (N = 4) was significantly reduced, to 0.25 ± 0.07, in PPE‐treated mice (N = 4) (p = 0.038). This study is the first application of multiple breath ventilation imaging to spontaneously breathing mice, and shows that this methodology is sensitive to differences in the pulmonary ventilation. This methodology is expected to improve simplicity as well as noninvasiveness when assessing regional ventilation in small rodents. Copyright © 2014 John Wiley & Sons, Ltd.     

Agminated fibroblastic connective tissue nevus in a 1‐year‐old boy

Fibroblastic connective tissue nevus (FCTN) is a benign cutaneous mesenchymal lesion characterized by proliferation of CD34‐positive fibroblastic/myofibroblastic spindle‐shaped cells. We report a case of agminated FCTN on the right lower abdomen of a 1‐year‐old boy.     

Mass Protection Program of Perinatal Hepatitis B Virus Infection in Japan and Impact of an Optional Booster Vaccination on Its Efficacy

We assessed the efficacy of a government-sponsored mass protection program in Osaka, Japan, for perinatal HBV infection in infants born to HBeAg positive HBV carrier mothers. We also evaluated the impact of optional follow-up procedures in such infants, including an evaluation of anti-HBs response and a booster dose of HBV vaccine for poor responders. The results demonstrated that this mass protection program protected 94.4% of the infants from perinatal HBV infection in the Osaka area. However, the proportion of infants with an unprotective level of anti-HBs was higher in the standard group than in the follow-up group both at 1.0 and 1.5 years of age, which was also the case for HBV events. Furthermore, the present study showed that a booster dose of vaccine in poor responders was very effective in promoting an anti-HBs response. In conclusion, we recommend that a follow-up blood test to confirm a response of anti-HBs to HBV vaccine should be performed at 4–8 weeks after the third injection of HBV vaccine in infants born to HBeAg positive HBV carrier mothers. We also recommend that a booster injection of HBV vaccine should be immediately given to poor responding infants who otherwise are at a considerable risk of developing HBV infection in late infancy.     

Cancer detection using a PET tracer, 11C-glycylsarcosine, targeted to H+/peptide transporter.

H+/peptide transporter, PEPT1, is functionally expressed in some human cancer cell lines and might be a candidate molecular target for detection of cancers in vivo using PET. The aim of the present study was to establish a novel tumor-imaging technology using a PET tracer targeted to H+/peptide transporter(s). We also compared the tracer with 18F-FDG, focusing on the specificity of their accumulation between tumor and inflammatory tissues. METHODS: A dipeptide PET tracer, 11C-glycylsarcosine (11C-Gly-Sar), was injected intravenously into athymic mice transplanted with human pancreatic, prostate, and gastric cancer cells. The distribution patterns of 11C-Gly-Sar and 18F-FDG in the tumor-bearing mice, and in mice with inflammatory tissue, were assessed by imaging with a positron planar imaging system (PPIS). Tissue distributions of tracer radioactivity were also measured. The expression levels of PEPT1 and PEPT2 (PEPTs) proteins in tumor xenografts and inflammatory tissue were examined by immunohistochemical analysis. The messenger RNA expression levels of PEPTs in 58 available cancer cell lines were quantified by means of real-time polymerase chain reaction. RESULTS: All 3 tumor xenografts were well visualized with the PPIS after injection of 11C-Gly-Sar. Expression of PEPTs in those xenografts was confirmed by immunohistochemical analysis. Tumor-to-blood concentration ratios of 11C-Gly-Sar increased in a time-dependent manner and were much higher than unity. Most of the radioactivity found in the tumor tissue was recovered as the intact tracer. These results indicated that 11C-Gly-Sar was taken up by the PEPTs in tumor xenografts. It is noteworthy that 11C-Gly-Sar was minimally present in inflammatory tissues that expressed no PEPT1 or PEPT2 protein, whereas 18F-FDG was highly accumulated, with the values of the selectivity index being >25.1 and 0.72 for 11C-Gly-Sar and 18F-FDG, respectively. The mRNAs of PEPT1 and PEPT2 were expressed in 27.6% and 93.1%, respectively, of the cancer cell lines examined in the present study. CONCLUSION: The present study indicates that 11C-Gly-Sar is a promising tumor-imaging agent and is superior to 18F-FDG for distinguishing between tumors and inflammatory tissue. Because PEPTs were ubiquitously expressed in various types of tumor cells examined, 11C-Gly-Sar could be useful for the detection of many types of cancers.     

A case of carcinosarcoma arising in the submandibular gland.

A 54-year-old man presented with an 8-year history of a hard asymptomatic mass of the left submandibular area. Total excision of the left submandibular gland with radical neck dissection was performed under a diagnosis of a submandibular tumor, probably a malignant mixed tumor. The pathologic diagnosis was carcinosarcoma consisting of carcinomatous and sarcomatous elements. The epithelial component was composed of squamous cell carcinoma, undifferentiated carcinoma, and adenocarcinoma. The nonepithelial component was composed of chondrosarcoma, osteosarcoma, spindle cell sarcoma, rhabdomyosarcoma, and liposarcoma. In the central area of the tumor, a few remnants of benign pleomorphic adenoma were identifiable. The finding suggested that in our patient, the carcinosarcoma arose from a preexisting pleomorphic adenoma. In view of the expected aggressive nature of the tumor, the patient was treated with postoperative radiotherapy of 60 Gy total, in 30 daily fractions of 2 Gy, and chemotherapy. He currently remains well and free of disease 24 months after treatment.     

Hypertonic saline alters electrical barrier of the airway epithelium.

OBJECTIVE: The effect of tonicity changes in nebulizer solutions and irrigations on nasal mucosa is not well known. The present study aims to determine the basic mechanism of hypertonic solution on airway epithelial barrier. STUDY DESIGN AND SETTING: We investigated the electrical potential difference (PD) that is influenced by both active transport and the transepithelial electrical resistance of the epithelial mucosa in the human nose in vivo. The short circuit current (SCC) revealed net ion transport across the epithelium in the guinea pig trachea in vitro. Finally, the size dependency of macromolecules across the tracheal mucosa was determined in vitro using FITC-labeled dextrans of different sizes. RESULTS: PD was significantly decreased after topical application of hypertonic solution both in human and in guinea pig nose. SCC was significantly decreased after application of hypertonic solution. The transport of these dextrans from the basolateral to the apical side was not increased significantly after apical application of hypertonic saline. CONCLUSIONS: Hypertonic saline enhances the electrical permeability of the airway epithelial mucosa but not transport of macromolecule in the short term.     

A case-control study on factors relating to discontinuation of domiciliary care for the bedridden elderly in a metropolitan area]

A case-control study was conducted to examine factors relating to discontinuation of domiciliary care for the bedridden elderly in Shinagawa-ku, Tokyo. Cases were bedridden residents aged 65 years and over who had abandoned home care and applied for admission to live in a special nursing home for the aged between April and September in 1990 after being recipients of welfare allowances for disabled elderly. Controls were bedridden residents who continued to be given home care and matched to cases by sex, age and beginning month of the receiving of allowances. Among 50 cases and 94 controls interviewed, we obtained responses from 31 cases (62%) and 60 controls (64%). The main results were as follows: 1. During the home-care period, ADL (activities of daily living) of cases, especially walking ability, deteriorated more severely than in controls. Night delirium also appeared more frequently in cases. 2. The primary caregivers of cases were older than those of controls. Remarkable differences between cases and controls were observed in the family structure, the number of family members and the number of sub-caregivers. Cases tended to live alone or live with a spouse only, and with smaller number of family members and caregivers. 3. Case lived more frequently in houses with small numbers of rooms and without rooms of their own. 4. As regards utilization of domiciliary care services, cases used dispatch of home helpers more frequently and used day services less frequently.     

Changes in reversal of cupping in experimental glaucoma. Longitudinal study.

BACKGROUND: The authors prospectively and longitudinally studied changes in optic disc topography during spontaneous reduction of intraocular pressure (IOP) in five monkeys with experimental glaucoma, using a computerized image analyzing system (Topcon IMAGEnet). METHODS: Glaucomatous optic neuropathy was produced in one eye of each animal by repeated argon laser photocoagulation of the trabecular meshwork. The duration of follow-up was 12 months. After laser treatment, IOP fluctuated and tended to increase. Spontaneous reduction in IOP was frequently observed during follow-up. Changes in optic disc parameters (vertical and horizontal cup-to-disc ratios, rim area/disc area, cup volume/disc area) that accompanied a given magnitude of spontaneous reduction in IOP at the early stage of glaucoma (first 4 months of follow-up) were compared with those at the later stage of glaucoma (last 4 months of follow-up). RESULTS: All optic disc parameters improved significantly during IOP reduction at each stage of glaucoma. Although there was no significant difference between the two stages in the magnitude of IOP reduction, the extent of improvement in each disc parameter was significantly less in the later stage than in the early stage. In both stages, reversal of cupping occurred symmetrically in the vertical and horizontal dimensions. Expansion of the cup occurred symmetrically in the early stage, but this was predominantly vertical in the later stage. CONCLUSION: These results suggest that the extent of cupping reversal after IOP reduction may decrease with progressive glaucomatous damage in primate glaucoma.