Outcome of maintenance systemic chemotherapy with drug-free interval for metastatic urothelial carcinoma.

OBJECTIVE: Aiming to achieve long-term disease control, maintenance systemic chemotherapy (MSC) with a 1-3-month drug-free interval is continued in selected patients. We report our experience of MSC for metastatic urothelial carcinoma (UC). METHODS: Of 228 metastatic UC patients treated with systemic chemotherapy, 40 (17.5%, 40/228) had continuously undergone MSC. Data on the regimen, cycle number, and reason for the discontinuation of MSC were also collected. We analyzed OS from the initiation of MSC until death or the last follow-up, using the log-rank test to assess the significance of differences. RESULTS: The median number of cycles of chemotherapy was 6, and the responses were CR in 6, PR in 20, SD in 13, and PD in 1 before MSC. Gemcitabine plus CDDP or carboplatin was mainly performed as MSC (70%, 28/40). MSC was repeated quarterly in 30 (75%, 30/40), every two months in 8 (20%, 8/40), and with other intervals in 2 (5%, 2/40). Overall, a median of 3.5 cycles (range: 1-29) of MSC was performed. The reason for the discontinuation of MSC was PD in 24 (60%, 24/40), favorable disease control in 9 (22.5%, 9/40), and myelosuppression in 3 (7.5%, 3/40), and for other reasons in 2 (5%, 2/40). MSC was ongoing in 2 (5%, 2/40). The median OS was 27 months from the initiation of MSC. PS0 (P = 0.0169), the absence of lung metastasis (P = 0.0387), and resection of the primary site (P = 0.0495) were associated with long-term survival after MSC. CONCLUSIONS: In selected patients, long-term systemic chemotherapy could be performed with a drug-free interval. Our maintenance strategy with cytotoxic drugs may become one of the treatment options for long-term disease control.

A field survey of the partially edentate elderly: Investigation of factors related to the usage rate of removable partial dentures.

Although the shortened dental arch (SDA) concept has been known to all over the world, acceptance of the SDA concept as an oral health standard can be questionable from the patients' point of view, even if it is biologically reasonable. Furthermore, because the health insurance system covers removable partial dentures (RPDs) for all citizens in Japan, SDA patients seem to prefer to receive prosthetic treatment to replace the missing teeth. However, there were few field surveys to investigate the usage rate of RPDs in Japan. The purpose of this study was to determine the usage rate of RPDs in older Japanese subjects and to investigate the factors related to the usage of RPDs. Partially edentate participants (n = 390) were included in this study. Oral examinations were conducted to record several indices. The Cochran-Armitage trend test was used to evaluate the relationship between the number of missing teeth and the usage rate of RPDs. Chi-squared tests and logistic regression analysis were conducted to evaluate the factors related to the usage rate of RPDs. Usage of RPDs had a significantly positive association with the number of missing distal extension teeth and bilaterally missing teeth. The usage rate of RPDs increased as the number of missing distal extension teeth increased (P for trend < 0·001). The conclusion of this study was that participants with missing distal extension teeth had higher usage rates of RPDs than other participants, and the usage rate increased as the number of missing distal extension teeth increased.

Hybrid plasmonic-photonic modes in diffractive arrays of nanoparticles coupled to light-emitting optical waveguides.

We study the hybridized plasmonic-photonic modes supported by two-dimensional arrays of metallic nanoparticles coupled to light-emitting optical waveguides. Localized surface plasmon polaritons in the metallic nanoparticles can couple to guided modes in the underlying waveguide, forming quasi-guided hybrid modes, or to diffracted orders in the plane of the array, forming surface lattice resonances. We consider three kinds of samples: one sustains quasi-guided modes only, another sustains surface lattice resonances only, and a third sample sustains both modes. This third sample constitutes the first demonstration of simultaneous coupling of localized surface plasmons to guided modes and diffracted orders. The dispersive properties of the modes in the samples are investigated through light extinction and emission spectroscopy. We elucidate the conditions that lead to the coexistence of surface lattice resonances and quasi-guided hybrid modes, and assess their potential for enhancing the luminescence of emitters embedded in the coupled waveguide. We find the largest increase in emission intensity for the surface lattice resonances, reaching up to a factor of 20.

Influence of hypertension on pH of saliva in older adults.

BACKGROUND: Hypertension and/or antihypertensive medication reportedly induce dry mouth; however, an immediate relationship between salivary flow and hypertension has not been elucidated. OBJECTIVES: The purpose of the present study was to examine the association of hypertension and antihypertensive medication with salivary flow rate and pH in older adults. SUBJECTS: Subjects were independently living volunteers aged 60-78 years taking no medication (n = 138) or only antihypertensive medication (n = 27). Unstimulated saliva and stimulated saliva by the mastication method were collected, and salivary pH was measured. Hypertension was defined as systolic blood pressure of ≥ 140 mmHg and/or diastolic blood pressure of ≥ 90 mmHg. RESULTS: There was no significant correlation between either hypertension or intake of antihypertensive medication and unstimulated or stimulated salivary flow rate. However, multiple regression analysis showed that hypertension was significantly associated with pH of unstimulated saliva after controlling for other variables (ß = -0.270, P = 0.003). CONCLUSION: Hypertension regardless of antihypertensive medication was related to a lower pH of unstimulated saliva. Blood pressure might be a required consideration for maintenance of oral health in older individuals.

Light-emitting waveguide-plasmon polaritons.

We demonstrate the generation of light in an optical waveguide strongly coupled to a periodic array of metallic nanoantennas. This coupling gives rise to hybrid waveguide-plasmon polaritons (WPPs), which undergo a transmutation from plasmon to waveguide mode and vice versa as the eigenfrequency detuning of the bare states transits through zero. Near zero detuning, the structure is nearly transparent in the far-field but sustains strong local field enhancements inside the waveguide. Consequently, light-emitting WPPs are strongly enhanced at energies and in-plane momenta for which WPPs minimize light extinction. We elucidate the unusual properties of these polaritons through a classical model of coupled harmonic oscillators.

Detailed Arterial Anatomy and Its Anastomoses of the Sphenoid Ridge and Olfactory Groove Meningiomas with Special Reference to the Recurrent Branches from the Ophthalmic Artery.

BACKGROUND AND PURPOSE: Detailed arterial anatomy of the sphenoid ridge and olfactory groove meningiomas is complicated due to the fine angioarchitecture and anastomoses between each feeder. Herein, we present details of the arterial anatomy and the relationships of feeders in these lesions. MATERIALS AND METHODS: This study included 20 patients admitted to our department between April 2015 and March 2020. Conditions of subjects consisted of 16 sphenoid ridge meningiomas and 4 olfactory groove meningiomas. We mainly analyzed arterial anatomy using 3D rotational angiography and slab MIP images of these lesions. We also analyzed the anastomoses of each feeder. RESULTS: We found that 19 (95%), 15 (75%), and 15 (75%) lesions had feeders from the ophthalmic, internal carotid, and external carotid arteries, respectively. As feeders from the ophthalmic artery, recurrent meningeal arteries were involved in 18 lesions (90%). Fifteen lesions (75%) had anastomoses between each feeder. CONCLUSIONS: Most of the meningiomas in the sphenoid ridge and olfactory groove had feeders from the ophthalmic and internal carotid arteries. There were various anastomoses between each feeder. This is the first report to demonstrate the detailed arterial anatomy and frequency of recurrent branches from the ophthalmic artery and their anastomoses using detailed imaging techniques.

Inhibition of malic enzyme 1 disrupts cellular metabolism and leads to vulnerability in cancer cells in glucose-restricted conditions.

Malic enzyme 1 (ME1) regulates one of the main pathways that provide nicotinamide adenine dinucleotide phosphate (NADPH), which is essential for cancer cell growth through maintenance of redox balance and biosynthesis processes in the cytoplasm. In this study, we found that ME1 inhibition disrupted metabolism in cancer cells and inhibited cancer cell growth by inducing senescence or apoptosis. In glucose-restricted culture conditions, cancer cells increased ME1 expression, and tracer experiments with labelled glutamine revealed that the flux of ME1-derived pyruvate to citrate was enhanced. In addition, cancer cells showed higher sensitivity to ME1 depletion in glucose-restricted conditions compared to normal culture conditions. These results suggest that in a low-glucose environment, where glycolysis and the pentose phosphate pathway (PPP) is attenuated, cancer cells become dependent on ME1 for the supply of NADPH and pyruvate. Our data demonstrate that ME1 is a promising target for cancer treatment, and a strategy using ME1 inhibitors combined with inhibition of glycolysis, PPP or redox balance regulators may provide an effective therapeutic option.

Application of strain to orbital-spin-coupled system MnV2O4 at cryogenic temperatures within a transmission electron microscope.

The impact of mechanical stress on the morphology of crystallographic and magnetic domains in shape-controlled specimens of an orbital-spin-coupled system, MnV2O4, was examined by cryogenic Lorentz microscopy. Because of the difference in thermal expansion coefficients of MnV2O4 and the supporting Mo mesh, compression on the order of 0.01% was applied to the thin-foil specimens near the structural/magnetic phase transformation temperatures. The extent of compression was comparable to the lattice striction associated with the cubic-to-tetragonal phase transformation in MnV2O4 The applied strain thus clearly influenced the morphology of crystallographic domains (i.e. twinning configuration in the tetragonal phase) produced during cooling. The magnetic domain structure was entirely dependent on the configuration of twinning in the tetragonal phase. The observations in this study provided useful information for understanding the relationship between the crystallographic domains and the magnetic domains in MnV2O4.

Pulmonary alveolar microlithiasis: CT and pathologic findings in 10 patients.

BACKGROUND AND AIM: To evaluate CT findings of pulmonary alveolar microlithiasis and correlate the CT with the pathologic findings. METHODS: The study included 10 patients with pathologically proven microlithiasis. Two independent observers evaluated the presence, extent and distribution of the CT findings. CT findings were compared with those at autopsy in two patients and with transbronchial biopsy in eight patients. RESULTS: All patients had a myriad of calcified nodules measuring approximately 1 mm in diameter. Close apposition of the nodules resulted in areas of ground-glass attenuation and consolidation, which were the predominant abnormality on CT in all 10 patients, involving 41% +/- 16.3 (mean +/- SD) and 30% +/- 4.8 of the lung parenchyma, respectively. Calcifications were also seen along interlobular septa, bronchovascular bundles and pleura. Other findings included interlobular septal thickening, thickening of bronchovascular bundles, nodules, and subpleural cysts. There was a solid agreement between the observers for the presence (kappa value; 0.77) and extent (Spearman rank correlation; r = 0.81 to 1.0 p < 0.01) of abnormalities. Autopsy specimens demonstrated microliths in alveolar airspaces and along interlobular septa, bronchovascular bundles and pleura. Subpleural small cysts were shown to represent dilated alveolar ducts. CONCLUSION: Pulmonary microlithiasis is characterised by the presence of numerous small, calcified nodules, calcifications along interlobular septa, bronchovascular bundles and pleura, ground-glass opacities, consolidation, and subpleural cysts. The cysts represent dilated alveolar ducts.

Cyclosporin A inhibits H2O2-induced apoptosis of human fibroblasts.

Several clinical studies have shown that cyclosporin A (CsA) is effective for treating a variety of chronic inflammatory and autoimmune diseases. Because reactive oxygen species are believed to play a key role in the development of these diseases, causing cell apoptosis, we investigated whether CsA inhibits H2O2-induced apoptosis. Preincubation of human fibroblasts with CsA dose-dependently decreased H2O2-induced apoptosis. Apoptosis suppression by CsA was correlated with the prevention of mitochondrial dysfunction and caspase activation. Thus, our results suggest that the inhibition of apoptosis by CsA may at least partly contribute to the anti-inflammatory effect of CsA.

The stimulation of macrophage prostaglandin E2 and thromboxane B2 secretion by Streptococcus mutans insoluble glucans.

The effect of insoluble glucan synthesized by Streptococcus mutans on [3H]arachidonate metabolites secretion from peritoneal macrophages was studied. Insoluble glucans stimulated [3H]arachidonate release and secretion of prostaglandin E2 and thromboxane B2 from macrophages. In contrast, commercial soluble glucan (dextran) did not induce [3H]arachidonate release.

The enhancement of the hypomotility induced by small doses of haloperidol in the phase of dopaminergic supersensitivity in mice.

Dopaminergic supersensitivity in mice was induced by pretreatment with a single injection of haloperidol (4.8 mg/kg). After the pretreatment, further treatment with haloperidol (0.6 or 0.01 mg/kg) was made at varying intervals, and catalepsy, locomotor activity and homovanillic acid (HVA) were measured. The intensity of the supersensitivity was evaluated by enhanced apomorphine (1 mg/kg)-induced climbing behavior. Supersensitivity was displayed on the 2nd and the 4th day. The cataleptogenic effect of haloperidol (0.6 mg/kg) was significantly weakened on the 1st, 2nd and 4th days. The motor inhibitory effect of haloperidol (0.01 mg/kg) increased on the 1st, 2nd and 4th days. Homovanillic acid was measured in the striatum and the prefrontal cortex on the 2nd day. Haloperidol (0.6 mg/kg) increased the concentrations of HVA in both regions of the brain. The increase in the concentrations of HVA in the striatum was blunted after the pretreatment, but such tolerance did not develop in the prefrontal cortex. Haloperidol (0.01 mg/kg) did not influence the concentration of HVA in both regions. These results suggest that the behavioral effect of a small dose of haloperidol may be enhanced, rather than reduced, in the phase of supersensitivity.

Alpha-sialyl cholesterol reverses AF64A-induced deficit in passive avoidance response and depletion of hippocampal acetylcholine in mice.

1. The effect of alpha-sialyl cholesterol (alpha-SC; alpha-D-N-acetylneuraminyl cholesterol) on disturbances of the central cholinergic system induced by ethylcholine mustard aziridinium ion (AF64A) and by scopolamine were studied by means of a step-down passive avoidance response and locomotor activities in mice. The levels of acetylcholine (ACh) in certain regions of the brain were measured to assess the neurochemical recovery promoted by alpha-SC. 2. Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) impaired the 24 h retention latencies of animals in a dose-dependent manner, and scopolamine (0.5 mg kg-1, i.p.) also impaired the retention performance. Administration of alpha-SC (1 and 4 mg kg-1, p.o.) once daily for 13 days improved the retention performance in AF64A-treated animals in a dose-dependent manner, but not in the scopolamine-treated animals. 3. Treatment with AF64A (2.5, 5 and 10 nmol, i.c.v.) and scopolamine (0.5 mg kg-1, i.p.) increased vertical and horizontal locomotor activities. alpha-SC dose-dependently attenuated the increase in locomotor activities induced by 2.5 nmol of AF64A, but not the locomotor activities caused by 5 or 10 nmol of AF64A, or scopolamine (0.5 mg kg-1, i.p.). 4. The deficit retention performance of AF64A-treated animals was associated with depletion of ACh levels in the hippocampus, but not in the septum or cerebral cortex. Administration of alpha-SC to AF64A-treated animals dose-dependently reversed the depletion of ACh levels in the hippocampus. 5. The results indicate that alpha-SC had significant effects after oral administration of AF64A-treated animals. The behavioural recovery promoted by alpha-SC may be based on the reversal of ACh depletion in the hippocampus.

Stimulation of serotonin synthesis in rat brain after antiepilepsirine, an antiepileptic piperine derivative.

Piperine and two of its derivatives, antiepilepsirine (AE or 3,4-methylendioxycynnamoylpiperine) and compound 7448 (N-isopropyl 3 (4 chloro-phenyl) propenoylamide) are very effective in stimulating serotonin (5HT) synthesis. AE raises the ratio of free-to-bound tryptophan (TP) in plasma and induces a long-lasting increase of this aminoacid in brain. At the same time in striatum and limbic area it causes a lasting increase in 5 hydroxyindolacetic acid (5HIAA) a 5HT metabolite and to a lesser extent, an increase in the levels of the monoamine itself. Together with this action on 5HT metabolism we found that AE caused release of 3H-5HT from an in vitro synaptosomal preparation. It thus appears that piperine and its derivatives AE and compound 7148 affect the central serotonergic system.

Binding of myosin and its subfragment-1 with antibodies specific to the two heads of the myosin molecule.

It was shown by Miyanishi et al. [Miyanishi, T., Maita, T., Matsuda, G., and Tonomura, Y. (1982) J. Biochem. 91, 1845-1853] that the amino acid sequence around the reactive lysine residue is different between head B (Pi-burst head) and head A of the myosin molecule. Thus, we synthesized these two peptides, and prepared rabbit polyclonal antibodies against them. Each antibody bound strongly with both peptides. However, the binding of the antibodies with S-1 was inhibited by the peptide used for the antigen but unaffected by the non-antigen peptide, suggesting that only antibodies specific to each head can bind with S-1. Myosin was absorbed by either antibody A or B, which was immobilized on protein A in Staphylococcus aureus cells. However, half of S-1 was absorbed by each of the antibodies. The S-1 prepared showed about 0.5 mol of initial Pi-liberation per mol of S-1. The Pi-burst size of S-1 unbound to the immobilized anti-A antibody increased to almost 1 mol/mol S-1, while that of S-1 unbound to the anti-B antibody decreased to 0.15 mol/mol S-1. These results suggest the existence of two kinds of heads in the myosin molecule.

Structure of heads A and B of myosin studied by tryptic digestion of myosin subfragment-1.

We studied the difference in the structure of head B (P1-burst head) and head A of myosin by limited tryptic digestion of myosin subfragment-1 (S-1), and using antibodies (anti-A and anti-B) which bind specifically with each head. The antibodies were prepared using peptides with sequences identical to those around the reactive lysine residue of heads A and B. When myosin subfragment-1 (S-1) was cleaved limitedly by trypsin, S-1 heavy chain (100 kDa) was digested into fragments of 25, 50, and 20 kDa. Two fragments with molecular masses of 75 and 27 kDa were transiently produced in the initial phase of digestion. Anti-A and anti-B antibodies bound only with peptides that contained the reactive lysine residue [S-1 heavy chain (100 kDa), 75-, 27-, and 25-kDa peptides], thus showing specific binding with antigen peptide. However, the 27-kDa fragment bound more strongly with anti-B antibody than with anti-A antibody. When S-1 was separated into fractions rich in S-1A and S-1B using insoluble anti-A or anti-B antibody, each antibody bound more strongly with the S-1 heavy chain (100 kDa) of its corresponding fraction by Western immunoblotting. These results suggest that the antibodies react specifically with peptides even after SDS-PAGE and membrane-blotting, and that the structure of the 25 kDa 50 kDa junction differs between heads A and B of myosin.

AF64A disrupts retrieval processes in long-term memory of mice.

Intracerebroventricular (i.c.v.) injection of ethylcholine mustard aziridinium ion (AF64A) in mice caused a reversible impairment of retrieval processing in long-term memory. After long retention intervals (1-3 weeks), AF64A-treated mice demonstrated marked impairment of behavioural performance previously acquired in a complex multiple maze task. This behavioural deficit was dose dependently ameliorated by the administration of oxotremorine. In parallel with the behavioural deficit, AF64A selectively decreased acetylcholine (ACh) levels in the hippocampus. These findings suggest that the reversible behavioural deficit induced by AF64A should be regarded as a retrieval failure in long-term memory, and not as a retention failure. This failure was largely associated with dysfunction of the cholinergic neuronal system in the hippocampus.

A comparison of the bactericidal effects and cytotoxic activity of three types of oxidizing water, prepared by electrolysis, as chemical dental plaque control agents.

Acid oxidizing water (AOW), neutral oxidizing water (NtOW) and acid oxidizing water with a low available chlorine concentration (AOW-LC) may be obtained by electrolyzing a solution of tap water containing various quantities of NaCl and HCl. This study compared the bactericidal effects of these waters on cariogenic and periodontopathogenic bacteria and their cytotoxicities against epithelial cells. AOW, NtOW and AOW-LC showed considerable bactericidal effects. The cytotoxicity of AOW-LC was significantly lower than the other solutions tested (P<0.0001). The results indicated that the three types of oxidizing water had similar activity in inhibiting bacterial plaque formation as conventional chemical plaque-control agents.

Glycylprolyl dipeptidylaminopeptidase from Bacteroides gingivalis.

Dipeptidyl aminopeptidase activity was found in the culture medium of Bacteroides gingivalis 381. The enzyme, hydrolyzing glycylprolyl-4-methylcoumaryl-7-amide, was purified 750-fold from culture medium by ammonium sulfate precipitation, Sephadex G-200 gel filtration, and DEAE Bio Gel A column chromatography. The molecular weight, determined by gel filtration, was approximately 160,000. The isoelectric point of the enzyme, estimated by isoelectric focusing using polyacrylamide disk gel electrophoresis, was about pH 6.2. The optimum pH of the enzyme was about 8.0, and the Km value was 0.05 mM. The enzyme activity was strongly inhibited by phenylmethylsulfonylfluoride and diisopropylfluorophosphate. The purified enzyme specifically cleaved glycylprolyl dipeptide from partially digested type I collagen.