Validation of cardiac 123I-MIBG scintigraphy in patients with Parkinson’s disease who were diagnosed with dopamine PET

Purpose  

The aim of this study was to evaluate the diagnostic potential of cardiac ¹²³I-labelled metaiodobenzylguanidine (¹²³I-MIBG) scintigraphy in idiopathic Parkinson’s disease (PD). The diagnosis was confirmed by positron emission tomography (PET) imaging with ¹¹C-labelled 2β-carbomethoxy-3β-(4-fluorophenyl)-tropane (¹¹C-CFT) and ¹¹C-raclopride (together designated as dopamine PET).     

Deregulated matriptase activity in oral squamous cell carcinoma promotes the infiltration of cancer‐associated fibroblasts by paracrine activation of protease‐activated receptor 2

Cancer‐associated fibroblasts (CAFs) are known to contribute to cancer progression. We have reported that cell surface expression of hepatocyte growth factor activator inhibitor 1 (HAI‐1) is decreased in invasive oral squamous cell carcinoma (OSCC) cells. This study examined if HAI‐1‐insufficiency contributes to CAF recruitment in OSCC. Serum‐free conditioned medium (SFCM) from a human OSCC line (SAS) stimulated the migration of 3 human fibroblast cell lines, NB1RGB, MRC5 and KD. SFCM from HAI‐1‐knockdown SAS showed an additive effect on the migration of NB1RGB and MRC5, but not KD. SAS SFCM induced protease‐activated receptor‐2 (PAR‐2) expression in NB1RGB and MRC5, but not in KD, and a PAR‐2 antagonist blocked the stimulatory effect of HAI‐1 knockdown on migration of the PAR‐2 expressing cell lines. Moreover, HAI‐1‐deficient SFCM showed additive stimulatory effects on the migration of wild‐type but not PAR‐2‐deficient mouse fibroblasts. Therefore, the enhanced migration induced by HAI‐1‐insufficiency was mediated by PAR‐2 activation in fibroblasts. This activation resulted from the deregulation of the activity of matriptase, a PAR‐2 agonist protease. HAI‐1 may thus prevent CAF recruitment to OSCC by controlling matriptase activity. When HAI‐1 expression is reduced on OSCC, matriptase may contribute to CAF accumulation by paracrine activation of fibroblast PAR‐2. Immunohistochemical analysis of resected OSCC revealed increased PAR2‐positive CAFs in 35% (33/95) of the cases studied. The increased PAR‐2 positive CAFs tended to correlate with infiltrative histology of the invasion front and shorter disease‐free survival of the patients.     

Beyond the midbrain atrophy: wide spectrum of structural MRI finding in cases of pathologically proven progressive supranuclear palsy

Purpose

Recently, it has been recognized that pathologically proven progressive supranuclear palsy (PSP) cases are classified into various clinical subtypes with non-uniform symptoms and imaging findings. This article reviews essential imaging findings, general information, and advanced magnetic resonance imaging (MRI) techniques for PSP and presents these MRI findings of pathologically proven typical and atypical PSP cases for educational purposes.

Methods

With the review of literatures, notably including atypical pathologically proven PSP cases, MRI and clinical information of 15 pathologically proven typical and atypical PSP cases were retrospectively evaluated.

Results

In addition to typical symptoms, PSP patients can exhibit atypical symptoms including levodopa-responsive parkinsonism, pure akinesia, non-fluent aphasia, corticobasal syndrome, and predominant cerebellar ataxia. As well as clinical symptoms, the degree of midbrain atrophy, a well-known imaging hallmark, is not consistent in atypical PSP cases. This fact has important implications for the limitation of midbrain atrophy as a diagnostic imaging biomarker of PSP pathology. Additional evaluation of other imaging findings including various regional atrophies of the globus pallidus, frontal lobe, cerebral peduncle, and superior cerebellar peduncle is essential for the diagnosis of atypical PSP cases.

Conclusion

It is necessary for radiologists to recognize the wide clinical and radiological spectra of typical and atypical PSP cases.

     

Use of organic solvents in large research institutions in Japan

Objectives

Laboratories in research institutions use organic solvents in research and development. Nevertheless, the types of solvents in use have been seldom reported. This study was initiated to elucidate types of organic solvents used in large research institutions in Japan, with a focus on possible different use among research fields.

Methods

In 2010–2011, 4517 laboratories in seven large research institutions were visited. In accordance with legal stipulations, air in each laboratory was collected in polyvinyl fluoride bags and analyzed by direct injection into a gas-chromatograph for 47 types of organic solvents. In evaluation, the laboratories were grouped by 5 research fields, i.e., agriculture, biology, medicine, natural science, and technology and engineering.

Results

Types of organic solvents commonly used in research activities were not diverse. Those commonly used were chloroform and 1,2-dichloroethane out of 7 Group 1 organic solvents (with high toxicities); 6 organic solvents, i.e., acetone and methyl alcohol in general, ethyl acetate, hexane and toluene in technology and engineering laboratories; and xylenes in medical fields out of 40 Group 2 organic solvents (with relatively low toxicities). Judging from solvent vapor concentrations, work environments in more than 99 % of laboratories were considered adequate. Nevertheless, use of chloroform in high-performance liquid chromatography (HPLC) resulted in inadequate environments in 30 laboratories (0.7 %).

Conclusions

Organic solvents commonly used were not very diverse. Work environments in research laboratories were generally good, but the environment with use of chloroform in HPLC analysis remained yet to be improved.     

5-Fluorouracil ointment for the treatment of otitis media with effusion

OBJECTIVES/HYPOTHESIS: Our aim was to evaluate the combined effect of 5-fluorouracil (5-FU) and myringotomy for the treatment of otitis media with effusion (OME). OME is usually treated with medication, myringotomy, or insertion of a ventilation tube (VT). Except for VT insertion, however, treatment effects are short-lived. VT insertion has numerous sequelae: increased susceptibility to infection, large perforation of the tympanic membrane, cholesteatoma, and eventual hearing deterioration. We estimated the depressant action of 5-FU on normal cell proliferation in vitro. In addition, clinically, we assessed whether 5-FU has the potential to prolong the effect of myringotomy. STUDY DESIGN: An in vitro study and a clinical study were conducted. MATERIALS AND METHODS: In study I, fibroblasts harvested from the peritoneum of three green fluorescent protein transgenic mice were cultured with different doses of 5-FU. After 2 weeks, their proliferation rates were compared. In study II, patients (54 males, 47 females) were selected randomly from a group of patients with intractable OME. Myringotomy with or without a single dose of 5-FU ointment (approximately 0.10-0.30 mg) was performed in group I (n = 64) and group II (n = 37), respectively. The natural closure rates of the tympanic membrane were assessed in both groups. RESULTS: In vitro, 5-FU inhibited the growth of fibroblasts in a dose-dependent manner. The average time to tympanic membrane closure was 20.5 days in group I and 8.1 days in group II. No adverse events were observed in either group. CONCLUSIONS: Topical application of 5-FU ointment is useful in prolonging the effect of myringotomy. 5-FU ointment therapy is easy, safe, and cost-effective and may be of wide application.     

Bone regeneration of canine skull using bone marrow-derived stromal cells and beta-tricalcium phosphate

OBJECTIVE: The aim of this study was to regenerate high-quality cranial bone using tissue engineering techniques, with subsequent extension to clinical application. Our previous study with a 3-month observation period indicated that a composite scaffold composed primarily of beta-tricalcium phosphate (TCP) had the potential for cranial bone regeneration. In this study, we investigated whether bone marrow derived stromal cells (BSCs) could promote the regeneration of cranial bone as determined after 3 and 6 months. STUDY DESIGN: The pilot study was conducted with 14 adult beagle dogs. MATERIALS AND METHODS: Craniotomy was performed in the same manner used clinically. The bone defect (2 x 2 cm) was created at each canine temporoparietal region. The test animals were divided into three groups. In group I, the bone defect was closed by replacing the original free bone flap without filling the residual gaps. In group II, the gap was filled with a composite scaffold consisting of collagen coated beta-TCP and autologous bone fragments with fibrin glue. In group III, autologous cultured BSCs and the composite scaffold were used to fill the gap. The sites of craniotomy were analyzed with three-dimensional computed tomography and histologic examination 3 and 6 months after the operation. RESULTS: Bone regeneration was observed in groups II and III, with more extensive formation in group III than in group II. In group I, bone regeneration was not observed. CONCLUSION: This study showed that BSCs have the potential to promote cranial bone regeneration and confirmed the efficacy of a composite scaffold made of beta-TCP and autologous bone fragments with fibrin glue.     

Side population cells in the human vocal fold

OBJECTIVES: The regenerative processes of the vocal fold, or the existence of stem cells in the folds, are unknown. Side population (SP) cells are defined as cells that have the ability to exclude the DNA binding dye, Hoechst 33342. They are regarded as a cell population enriched with stem cells and can be isolated from non-SP cells by a fluorescence-activated cell sorter. This study was designed to determine whether SP cells exist in the human vocal fold, as a first step in elucidating the regenerative mechanisms of the vocal fold. METHODS: Seven human excised larynges were used in this study. Two were used for fluorescence-activated cell sorter analysis, and 5 were subjected to immunohistochemical analysis with antibodies against an adenosine triphosphate binding cassette transporter family member, ABCG2, which is expressed in SP cells. RESULTS: The number of SP cells in the human vocal fold was about 0.2% of the total number of cells. ABCG2-positive cells were identified in both the epithelium and subepithelial tissue throughout the entire vocal fold. CONCLUSIONS: This preliminary study demonstrated the existence of SP cells in the human vocal fold. Further studies are warranted to clarify how these cells work in the vocal fold, particularly in the regenerative process.