Effect of Escherichia coli on phospholipid monolayers: surface tensiometry and Brewster angle microscopy measurements.

The effect of Escherichia coli (E. coli) cells on two phospholipids [dipalmitoyl phosphatidylcholine (DPPC) and dimyristoyl phosphatidylcholine (DMPC)] monolayers at the surface of a 1.5 wt% NaCl salt solution has been investigated using surface tension measurement and Brewster angle microscopy. The results showed that a DPPC monolayer that has an elastic structure was changed in morphology by interaction with E. coli cells, whereas a DMPC monolayer that has an expandable structure did not change in morphology. In particular, the morphology changed significantly around the liquid-expanded (LE)-liquid-condensed (LC) phase transition point for the DPPC monolayer. It was found that the LE-LC phase transition range in a DPPC monolayer was sensitive to influence from the outside of the monolayer such as the action of E. coli cells. Such a monolayer has the potential for application as a membrane sensor for detecting a small amount of bacteria in a short time.

Neuromyelitis optica spectrum disorder secondary to treatment with anti-PD-1 antibody nivolumab: the first report.

BACKGROUND: Immune checkpoint blockade is developed as standard treatment for non-small cell lung cancer. However immune-related adverse events (irAE) have still unknown complications. Here, we report a patient with lung squamous cell carcinoma who developed neuromyelitis optica spectrum disorder with nivolumab. CASE PRESENTATION: A 75-year-old Japanese man with lung squamous cell carcinoma was administered nivolumab as second-line treatment. Two months after treatment with nivolumab, he presented acute paralysis in the bilateral lower limbs, sensory loss. Spinal magnetic resonance imaging showed T2 hyperintense lesions between C5-6 and Th12-L1. He was diagnosed with neuromyelitis optica spectrum disorder (NMOSD) by anti-aquaporin-4 antibody-positive in the serum and other examinations. After treatment, steroid reactivity was poor. CONCLUSION: This is the first patient who developed anti-AQP4 antibody-positive NMOSD as a nivolumab-induced irAE. Clinicians should be aware of this kind of potential neurological complication by using immune check point inhibitor and start the treatment of this irAE as soon as possible.

Observation of Zn-photoprotoporphyrin red Autofluorescence in human bronchial cancer using color-fluorescence endoscopy.

BACKGROUND: We observed red autofluorescence emanating from bronchial cancer lesions using a sensitive color-fluorescence endoscopy system. We investigated to clarify the origin of the red autofluorescence. METHODS: The wavelengths of the red autofluorescence emanating from lesions were measured in eight patients using a spectrum analyzer and compared based on pathologic findings. Red autofluorescence at 617.3, 617.4, 619.0, and 617.1 nm was emitted by normal bronchus, inflamed tissue, tissue exhibiting mild dysplasia, and malignant lesions, respectively. Protoporphyrin, uroporphyrin, and coproporphyrin, the major porphyrin derivatives in human blood, were purchased to determine which porphyrin derivative is the source of red fluorescence when acquired de novo. We synthesized photoporphyrin, Zn-protoporphyrin and Zn-photoprotoporphyrin from protoporphyrin. RESULTS: Coproporphyrin and uroporphyrin emitted only weak fluorescence. Fluorescence was emitted by our synthesized Zn-photoprotoporphyrin at 625.5 nm and by photoprotoporphyrin at 664.0 nm. CONCLUSIONS: From these results, we conclude that Zn-photoprotoporphyrin was the source of the red autofluorescence observed in bronchial lesions. Zn-protoporphyrin is converted to Zn-photoprotoporphyrin by radiation with excitation light. Our results suggest that red autofluorescence emanating from Zn-photoprotoporphyrin in human tissues could interfere with photodynamic diagnosis using porphyrin derivatives such as Photofrin® and Lazerphyrin® with a sensitive endoscopy system, because color cameras cannot differentiate Zn-photoprotoporphyrin red fluorescence from that of other porphyrin derivatives.

Whole brain analysis of postmortem density changes of grey and white matter on computed tomography by statistical parametric mapping.

OBJECTIVES: This study examined the usefulness of statistical parametric mapping (SPM) for investigating postmortem changes on brain computed tomography (CT). METHODS: This retrospective study included 128 patients (23 - 100 years old) without cerebral abnormalities who underwent unenhanced brain CT before and after death. The antemortem CT (AMCT) scans and postmortem CT (PMCT) scans were spatially normalized using our original brain CT template, and postmortem changes of CT values (in Hounsfield units; HU) were analysed by the SPM technique. RESULTS: Compared with AMCT scans, 58.6 % and 98.4 % of PMCT scans showed loss of the cerebral sulci and an unclear grey matter (GM)-white matter (WM) interface, respectively. SPM analysis revealed a significant decrease in cortical GM density within 70 min after death on PMCT scans, suggesting cytotoxic brain oedema. Furthermore, there was a significant increase in the density of the WM, lenticular nucleus and thalamus more than 120 min after death. CONCLUSIONS: The SPM technique demonstrated typical postmortem changes on brain CT scans, and revealed that the unclear GM-WM interface on early PMCT scans is caused by a rapid decrease in cortical GM density combined with a delayed increase in WM density. SPM may be useful for assessment of whole brain postmortem changes. KEY POINTS: • The original brain CT template achieved successful normalization of brain morphology. • Postmortem changes in the brain were independent of sex. • Cortical GM density decreased rapidly after death. • WM and deep GM densities increased following cortical GM density change. • SPM could be useful for assessment of whole brain postmortem changes.

Effect of the forward-projected model-based iterative reconstruction solution algorithm on image quality and radiation dose in pediatric cardiac computed tomography.

BACKGROUND: Some iterative reconstruction algorithms are useful for reducing the radiation dose in pediatric cardiac CT. A new iterative reconstruction algorithm (forward-projected model-based iterative reconstruction solution) has been developed, but its usefulness for radiation dose reduction in pediatric cardiac CT is unknown. OBJECTIVE: To investigate the effect of the new algorithm on CT image quality and on radiation dose in pediatric cardiac CT. MATERIALS AND METHODS: We obtained phantom data at six dose levels, as well as pediatric cardiac CT data, and reconstructed CT images using filtered back projection, adaptive iterative dose reduction 3-D (AIDR 3-D) and the new algorithm. We evaluated phantom image quality using physical assessment. Four radiologists performed visual evaluation of cardiac CT image quality. RESULTS: In the phantom study, the new algorithm effectively suppressed noise in the low-dose range and moderately generated modulation transfer function, yielding a higher signal-to-noise ratio compared with filtered back projection or AIDR 3-D. When clinical cardiac CT was performed, images obtained by the new method had less perceived image noise and better tissue contrast at similar resolution compared with AIDR 3-D images. CONCLUSION: The new algorithm reduced image noise at moderate resolution in low-dose CT scans and improved the perceived quality of cardiac CT images to some extent. This new algorithm might be superior to AIDR 3-D for radiation dose reduction in pediatric cardiac CT.

Evaluation of the Effect of Attenuation Correction by External CT in a Semiconductor SPECT.

The discovery of NM530c with a cadmium-zinc-telluride detector (CdZnTe-SPECT) is superior to the conventional Anger-type SPECT with a sodium-iodide detector (NaI-SPECT) in terms of sensitivity and spatial resolution. However, in the clinical example, even in CdZnTe-SPECT, a count decrease in myocardium due to the attenuation of the gamma ray is an issue. This study was conducted to evaluate the effect of computed tomography attenuation correction (CTAC) in CdZnTe-SPECT with the help of external CT. We evaluated the revision effect of uniformity, influence by the difference in attenuation distance, contrast ratio, an uptake rate using the heart phantom. As a result of the phantom studies, a good revision effect was obtained. In the clinical study, there was a statistical significant difference between the contrast ratio before and after CTAC in the inferior wall. In addition, the contrast ratio before and after CTAC in CdZnTe-SPECT image was equal to those of NaI-SPECT image. It was suggested that CTAC using external CT in CdZnTe-SPECT was clinically useful for inferior wall.

Evaluation of Resolution Recovery for Each Collimator in Brain Perfusion Image.

PURPOSE: This study aimed to verify the resolution recovery for each collimator in the brain perfusion image. METHOD: To verify the effect of the resolution recovery for each collimator, we evaluated via the three-dimensional brain phantom (phantom) and the normal brain perfusion single photon emission computed tomography (SPECT) data. These data were reconstructed using the three-dimensional ordered subset expectation maximization method (3D-OSEM) (Evolution for boneTM) that was performed with scatter correction, attenuation correction, and resolution recovery (RR). The performance of resolution recovery was evaluated in the two collimator systems (ELEGP and MEGP) reconstruction condition via the contrast value, mean counts, normalized mean square error (NMSE), and regional brain activity. RESULT: In the "with resolution recovery (+RR)", the NMSE indicated minimum value with SI (subset×iteration) = 100, cut-off frequency (Fc) = 0.50 cycles/cm. The contrast value in the "+RR" increased 20% for the cortical region and decreased 28% and 6% at ELEGP collimator and MEGP collimator for the central region, as compared to the "without resolution recovery (-RR)". In the phantom study, the error of the brain activity using MEGP collimator at the temporal lobe and sub-lobar decreased 15%, compared with ELEGP collimator in the + RR. In the clinical study, the error of the regional brain activity using MEGP collimator in the "+RR" increased from 3% to 8%, compared with "-RR". DISCUSSION: The accurate resolution recovery was obtained at SI = 100 and Fc = 0.50 cycles/cm. The contrast value and regional brain activity at the central region decreased due to incomplete resolution recovery by use of ELEGP collimator.

[Usefulness of Iterative Reconstruction Method in the Field of Acute Cerebral Infarction Computed Tomography Examination].

We evaluated clinical images to investigate the usefulness of adaptive iterative dose reduction algorithm (AIDR) in the field of acute cerebral infarction. We did receiver operating characteristic (ROC) analysis by 4 radiologists using 50 clinical images (abnormal case=24, normal case=26) which were reconstructed by AIDR and filtered back projection (FBP). The area under the curve (AUC) value from average ROC curve of observers were 0.79 with the FBP and 0.87 with the AIDR (P=0.31). The standard deviation of AUC was 0.06 with the FBP and 0.03 with the AIDR. More in detail, the AUC value of Expert group (over 10 years of experience) increased to 0.06 by using AIDR compared with FBP method. On the other hand, in Beginner group (less than 10 years of experience) there was 0.09 increase. Therefore, there was some possibility to reduce the variation of diagnostic accuracy among observer and the diagnostic accuracy improvement of the doctor in a few Experience group, by using AIDR for acute cerebral infarction computed tomography (CT) examination.

[Influence of a radioisotope from out of the effective field of view in a semiconductor single photon emission computed tomography scanner].

Discovery NM 530c (CZT SPECT) is a new single photon emission computed tomography (SPECT) scanner using a cadmium-zinc-telluride (CZT) solid-state semiconductor detector technology. Due to multi-pinhole collimator design of this system, each CZT detector facing different direction and be able to get incidence radioactivity from radioisotopes (RIs) existing outside of effective field of view (EFOV). The purpose of this study is to verify its impact and compare it to a conventional Anger-type SPECT scanner (Discovery NM/CT 670 pro). We used (99m)TcO4(-) as radiation source and set it outside of the EFOV at several different positions (height and angle) and scanned by both the cameras. As a result, CZT SPECT got more influence compared to Anger-type SPECT. The impact was different according to its height. When using other RIs in CZT SPECT room, it is important to confirm the appropriate position against CZT SPECT during scan.

[Comparison of Quantitative Value of Dopamine Transporter Scintigraphy Calculated from Different Analytical Software].

In the dopamine transporter scintigraphy there are two quantitative analysis softwares, DaTView and DaTQUANT. The quantitative value of both software has to be treated independently because there is a difference between them in the point of how to set the region of interest on the striatum and the background, calculation formula of quantitation. And also DaTQUANT has a capability of performing anatomical standardization which DaTView does not have. The aim of this study was to evaluate the accuracy of registration on DaTQUANT using a phantom, and to evaluate the correlation between the quantitative values between DaTView and DaTQUANT using clinical data. As a result, the accuracy of registration was acceptable. Regardless of the degree of accumulation in the striatum, there was a high correlation to each analysis software (r>0.85).

Morphology Observation of Two-Dimensional Monolayers of Model Proteins on Water Surface as Revealed by Dropping Method.

We have investigated the morphology of two-dimensional monolayers of gramicidin-D (GD) and alamethicin (Al) formed on the water surface by the dropping method (DM) using surface tension measurement (STm), Brewster angle microscopy (BAM), and atomic force microscopy (AFM). Dynamic light scattering (DLS) revealed that GD in alcoholic solutions formed a dimeric helical structure. According to the CD and NMR spectroscopies, GD molecules existed in dimer form in methanol and lipid membrane environments. The STm results and BAM images revealed that the GD dimer monolayer was in a liquid expanded (LE) state, whereas the Al monolayer was in a liquid condensed (LC) state. The limiting molecular area (A0) was 6.2 ± 0.5 nm2 for the GD-dimer and 3.6 ± 0.5 nm2 for the Al molecule. The AFM images also showed that the molecular long axes of both the GD-dimer and Al were horizontal to the water surface. The stability of each monolayer was confirmed by the time dependence of the surface pressure (π) observed using the STm method. The DM monolayer preparation method for GD-dimer and Al peptide molecules is a useful technique for revealing how the model biological membrane's components assemble in two dimensions on the water surface.

The Interaction between Anesthetic Isoflurane and Model-Biomembrane Monolayer Using Simultaneous Quartz Crystal Microbalance (QCM) and Quartz Crystal Impedance (QCI) Methods.

The interaction between anesthetic Isoflurane (Iso) and model-biomembrane on the water surface has been investigated using quartz crystal microbalance (QCM) and quartz crystal impedance (QCI) methods. The model-biomembranes used were dipalmitoyl phosphatidyl choline (DPPC), DPPC-palmitic acid (PA) mixture (DPPC:PA = 8:2), DPPC-Alamethicin (Al) mixture (DPPC:Al = 39:1), and DPPC-ß-Lactoglobulin (ßLG) mixture (DPPC:ßLG = 139:1) monolayers, respectively. The quartz crystal oscillator (QCO) was attached horizontally to each monolayer, and QCM and QCI measurements were performed simultaneously. It was found that Iso hydrate physisorbed on each monolayer/water interface from QCM and changed those interfacial viscosities from QCI. With an increase in Iso concentration, pure DPPC, DPPC-PA mixed, and DPPC-Al mixed monolayers showed a two-step process of Iso hydrate on both physisorption and viscosity, whereas it was a one-step for the DPPC-ßLG mixed monolayer. The viscosity change in the DPPC-ßLG mixed monolayer with the physisorption of Iso hydrate was much larger than that of other monolayers, in spite of the one-step process. From these results, the action mechanism of anesthetics and their relevance to the expression of anesthesia were discussed, based on the "release of interfacial hydrated water" hypothesis on the membrane/water interface.

Creation of cross-linked bilayer membranes that can incorporate membrane proteins from oligo-Asp-based peptide gemini surfactants.

We designed novel bilayer-forming amphiphiles based on the cyclic oligo-Asp-based peptide gemini (PG) surfactants cr-D2C12 and cr-D3C12, which consist of -Cys(Asp)nCys- (n = 2 or 3) as a core peptide and two Cys residues containing a dodecylamidomethyl group. Dynamic light scattering and transmission electron microscopy measurements revealed the formation of spherical bilayer membranes that could incorporate the light-harvesting antenna complex 2 (LH2) from Rhodopseudomonas acidophila . Furthermore, this proteoliposome-like conjugate could be assembled onto cationized glass and mica to form planar bilayer membranes incorporating LH2. Using atomic force microscopy, we observed LH2 protruding (ca. 1.2-1.5 nm) from flat terraces of the planar bilayer membranes formed from cr-D2C12 or cr-D3C12. Thus, our designed PG surfactants are a new class of bilayer-forming amphiphiles that may be applied to the study of various membrane proteins.

Application of peptide gemini surfactants as novel solubilization surfactants for photosystems I and II of cyanobacteria.

We designed novel peptide gemini surfactants (PG-surfactants), DKDKC12K and DKDKC12D, which can solubilize Photosystem I (PSI) of Thermosynecoccus elongatus and Photosystem II (PSII) of Thermosynecoccus vulcanus in an aqueous buffer solution. To assess the detailed effects of PG-surfactants on the original supramolecular membrane protein complexes and functions of PSI and PSII, we applied the surfactant exchange method to the isolated PSI and PSII. Spectroscopic properties, light-induced electron transfer activity, and dynamic light scattering measurements showed that PSI and PSII could be solubilized not only with retention of the original supramolecular protein complexes and functions but also without forming aggregates. Furthermore, measurement of the lifetime of light-induced charge-separation state in PSI revealed that both surfactants, especially DKDKC12D, displayed slight improvement against thermal denaturation below 60 °C compared with that using ß-DDM. This degree of improvement in thermal resistance still seems low, implying that the peptide moieties did not interact directly with membrane protein surfaces. By conjugating an electron mediator such as methyl viologen (MV(2+)) to DKDKC12K (denoted MV-DKDKC12K), we obtained derivatives that can trap the generated reductive electrons from the light-irradiated PSI. After immobilization onto an indium tin oxide electrode, a cathodic photocurrent from the electrode to the PSI/MV-DKDKC12K conjugate was observed in response to the interval of light irradiation. These findings indicate that the PG-surfactants DKDKC12K and DKDKC12D provide not only a new class of solubilization surfactants but also insights into designing other derivatives that confer new functions on PSI and PSII.

Small Dense Low-Density Lipoprotein Cholesterol Levels in Breakfast Skippers and Staple Foods Skippers.

AIMS: Skipping breakfast is known as a cardiovascular disease (CVD) risk. Recently, eating and dietary patterns have been varied in many countries, however, the mechanisms of promoting CVD are still unclear. Our goal was to assess the effects of eating and dietary patterns on CVD risk factors, with a focus on lipid parameters including serum concentration of small dense low-density lipoprotein cholesterol (sdLDL-C). METHODS: Subjects consisted of 27,997 Japanese men and women, who had medical check-up. Lipid parameters including sdLDL-C levels in breakfast skippers were compared with those in breakfast eaters. Lipid parameters in staple foods skippers were also compared with those in staple foods eaters. RESULTS: Breakfast skippers had significantly (p＜0.01) higher serum levels of median sdLDL-C than breakfast eaters in both genders (34.7 versus 32.0 mg/dL in men, 25.4 versus 24.9 mg/dL in women, respectively), and the same was true for sdLDL-C/LDL-C ratio (0.276 versus 0.260 in men, 0.218 versus 0.209 in women, respectively). Similarly, staple foods skippers had significantly higher sdLDL-C level than staple foods eaters in both genders (34.1 versus 31.6 mg/dL in men, 25.8 versus 24.7 mg/dL in women), and the same went for sdLDL-C/LDL-C ratio (0.278 versus 0.256 in men, 0.215 versus 0.208 mg/dL in women, respectively). CONCLUSION: Our data indicate that both skipping breakfast and having meals without staple foods increase serum sdLDL-C concentration and cause unfavorable lipid profiles, and then may promote CVD. These finding provide evidence for the importance of having breakfast and meals with staple foods for preventing CVD.

Design of Cell-Adhesive Shellac Derivatives and Endowment of Photoswitchable Cell-Adhesion Properties.

The emergence of new biodegradable cell-adhesion materials is an attractive topic in biomaterial chemistry, particularly for the development of cell incubation scaffolds and drug encapsulation materials used in in situ regenerative therapy. Shellac is a natural resin with unique film-forming properties and high miscibility with various chemicals, in addition to being biodegradable and nontoxic to biological systems. However, since native shellac does not adhere to mammalian cells, there have been no reports of using shellac to develop cell-adhesive biomaterials. In this study, we report on the development of cell-adhesive shellac derivatives through slight chemical modification. Shellac is a mixture of oligoesters that consists of hydroxyl fatty acids and resin acids, and therefore, all oligomers have one carboxylic acid group at the terminal. We discovered that a simple modification of hydrophobic chemical groups, particularly those containing aromatic groups in the ester form, could dramatically improve cell-adhesion properties for mammalian cells. Furthermore, by using photocleavable esters containing aromatic groups, we successfully endowed photoswitchable properties in cell adhesion. Given that shellac is a low-cost, biodegradable, and nontoxic natural resin, the modified shellacs have the potential to become new and attractive biomaterials applicable to in situ regenerative therapy.

Prediction of survival benefit using an automated bone scan index in patients with castration-resistant prostate cancer.

UNLABELLED: What's known on the subject? and What does the study add? A bone scan index (BSI) can quantify the extent of bone involvement and response to treatment, but it has not been widely accepted, because of its time-consuming nature. The study is the first to demonstrate that automated BSI calculated with a computer-assisted diagnosis system is effective in judging the chemotherapeutic response of bone metastatic lesions in patients with castration-resistant prostate cancer. OBJECTIVE: • To evaluate the value of an automated bone scan index (aBSI), calculated using a computer-assisted diagnosis system, to indicate chemotherapy response and to predict prognosis in patients with castration-resistant prostate cancer (CRPC) with bone metastasis. PATIENTS AND METHODS: • Forty-two consecutive CRPC patients underwent taxane-based chemotherapy between November 2004 and March 2011 at our institution. • The aBSIs were retrospectively calculated at the diagnosis of CRPC and 16 weeks after starting chemotherapy. • Cox proportional hazards regression models were applied to multivariate analyses with and without aBSI response in addition to the basic model. • Based on the difference in the concordance index (c-index) between each model, the prognostic relevance of adding the aBSI response was determined. RESULTS: • A decrease in aBSI was found in 28 patients (66.7%), whereas a response was shown by bone scan in only 23.8% of patients. • Patients with a reduction in aBSI had longer overall survival (OS) in comparison with the other patients (P= 0.0157). • Multivariate analysis without aBSI response showed that performance status (P= 0.0182) and PSA response (P= 0.0375) were significant prognosticators. • By adding the aBSI response to this basic model, the prognostic relevance of the model was improved with an increase in the c-index from 0.621 to 0.660. CONCLUSIONS: • The aBSI reflected the chemotherapy response in bone metastasis. • The index detected small changes of bone metastasis response as quantified values and was a strong prognostic indicator for patients with CRPC.

Subacute phase treatment of subperiosteal hematoma of the orbit with epidural hematoma in the frontal cranial fossa: case report.

BACKGROUND: Subperiosteal hematoma of the orbit is one of the rare lesions that cause exophthalmos after craniomaxillofacial trauma. Presently, there is no consensus for how to treat this disease. Although some reports have suggested a conservative type of therapy, others have recommended surgical treatments be done during the early stages. CASE PRESENTATION: This case report provides details on the clinical course of a 9-year-old girl with subperiosteal hematoma of the orbit. In this particular patient, a rare case of ipsilateral subfrontal extradural hematoma was also observed. Due to our performing the surgical intervention during the subacute stage, functional complications as well as cosmetic problems were avoided. CONCLUSION: Our results demonstrate that surgical treatments for subperiosteal hematoma of the orbit should be delayed until it can be confirmed that a patient has no other complications. On the other hand, once it has been confirmed that the patient has no other existing problems, immediate surgical therapy with a small skin incision followed by the setting of a drain is recommended in order to achieve an early resolution and avoid complications.