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Combination therapy with adefovir dipivoxil (ADV) and lamivudine (LAM) is recommended for patients infected with LAM-refractory hepatitis B virus (HBV). However, the effects of such therapy on renal function and serum phosphorus levels have not been fully evaluated. Combination therapy with ADV and LAM was given to 37 patients infected with LAM-refractory HBV, including 17 with hepatic cirrhosis. Serum HBV DNA levels decreased to below 2.6 log10 copies/mL in 23 (62%) of 37 patients at 12 months, 25 (78%) of 32 patients at 24 months, and 16 (84%) of 19 patients at 36 months. Except for one cirrhotic patient, serum alanine aminotransferase levels were below 50 IU/L in all patients during combination therapy. Serum creatinine levels increased in 14 (38%) of 37 patients, and serum phosphate levels decreased to below 2.5 mg/mL in 6 (16%) of 37 patients during combination therapy. Patients who received combination therapy for 36 months or longer had a significantly incidence of elevated serum creatinine levels. Fanconi syndrome occurred in a 57-year-old woman with cirrhosis after ADV was added to LAM. Combination therapy with ADV and LAM can maintain biochemical remission in patients with LAM-refractory HBV. However, the dosing interval of ADV should be adjusted according to renal function and serum phosphate levels in patients receiving long-term treatment. [ABSTRACT FROM AUTHOR]

Harmonic resistive multipliers that exploit the unique current–voltage (I–V) characteristics of Ag/Ge–(Sb)–Te/Pt resistive‐switching devices are demonstrated. For a Ge17Sb29Te54‐based device, an antisymmetric non‐linear I–V curve with a hump‐like structure at ±0.4 V is obtained, whereas for a Ge51Te49‐based device, an asymmetric non‐linear I–V curve with SET switching at +0.4 V and RESET switching at –0.1 V is observed. The Ge17Sb29Te54‐based device performs third harmonic multiplication for a 160 MHz input at 0 dBm, and sixth harmonic multiplication at 5 dBm under unbiased conditions without any matching circuit. For the latter device, biasing at a voltage of ±0.4 V leads to fifth harmonic multiplication, which is absent for a 0 dBm input under unbiased conditions. No harmonic multiplication is observed for an unbiased Ge51Te49‐based device due to its high resistance, but biasing at the switching voltage of 0.4 V leads to fourth harmonic multiplication for a 0 dBm input. The unique non‐linear characteristics of these devices suggest their potential for radio frequency applications. [ABSTRACT FROM AUTHOR]

Objective: The histological grade of parotid gland carcinoma (PGC) is an important prognostic factor; however, the diagnosis prior to treatment has been challenging to make. This study aimed to investigate whether the pretreatment clinical findings, including hematological inflammatory, nutritional, and immune markers, could predict the histological grade of PGC., Study Design: Retrospective study., Methods: We retrospectively enrolled 111 patients with PGC and evaluated the correlation between histological grade and pretreatment clinical findings such as age, sex, tumor staging, facial nerve paralysis, pain or tenderness, adhesion to the surrounding tissues or tumor immobility, and hematological markers., Results: Sixty patients (54%) were diagnosed with histological high-grade PGC. Univariate analysis revealed that age, T classification, N classification, TNM stage, facial nerve paralysis, adhesion/immobility, C-reactive protein (CRP), and CRP-to-albumin ratio (CAR) were significant predictors of PGC histological grade. On multivariate analysis, high T classification (T3, 4), high N classification (≥1), and elevated CRP (≥0.22 mg/dL) were independent predictors of high-grade PGC., Conclusions: Pretreatment T classification, N classification, and CRP are significant predictors of the histological grading of PGC. Our results are useful for treatment planning and obtaining appropriate informed consent from the patients before treatment., Level of Evidence: 4 Laryngoscope, 132:96-102, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: Previous studies have evaluated various markers as prognostic predictors in patients with many types of cancers. However, the influence of such factors on the outcomes of patients with parotid gland carcinoma (PGC) is unknown. This study investigated the roles of alternative markers in the prognoses of patients with PGC., Methods: Overall, 101 patients who underwent curative treatment for PGC were retrospectively evaluated, and their 5-year overall and disease-free survival rates were calculated. The prognostic values of clinical and pathologic factors were determined., Results: The 5-year overall and disease-free survival rates were 73.1% and 62.8%, respectively. Multivariate analysis revealed that a low lymphocyte-to-monocyte ratio (LMR), high T classification, high N classification, and perineural invasion were independent predictors of poor prognosis., Conclusions: Thus, we identified LMR as an independent prognostic factor for patients with PGC. Patients with low LMRs who are amenable to treatment may require adjuvant treatment to improve their prognoses., Level of Evidence: 4 Laryngoscope, 131:E864-E869, 2021., (© 2020 The Authors. The Laryngoscope published by Wiley Periodicals LLC. on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

The mechanism of action on biomolecules of N₂ gas plasma, a novel sterilization technique, remains unclear. Here, the effect of N₂ gas plasma on protein structure was investigated. BSA, which was used as the model protein, was exposed to N₂ gas plasma generated by short-time high voltage pulses from a static induction thyristor power supply. N₂ gas plasma-treated BSA at 1.5 kilo pulses per second showed evidence of degradation and modification when assessed by Coomassie brilliant blue staining and ultraviolet spectroscopy at 280 nm. Fourier transform infrared spectroscopy analysis was used to determine the protein's secondary structure. When the amide I region was analyzed in the infrared spectra according to curve fitting and Fourier self-deconvolution, N₂ gas plasma-treated BSA showed increased α-helix and decreased β-turn content. Because heating decreased α-helix and increased β-sheet content, the structural changes induced by N₂ gas plasma-treatment of BSA were not caused by high temperatures. Thus, the present results suggest that conformational changes induced by N₂ gas plasma are mediated by mechanisms distinct from heat denaturation., (© 2013 The Societies and Wiley Publishing Asia Pty Ltd.)

We describe the case of a 44-year-old Japanese woman with severe nodular erythematous skin lesions and arthritis mutilans who was admitted for further treatment of multicentric reticulohistiocytosis. Skin and synovial biopsies showed heavy infiltration with tartrate-resistant acid phosphatase-positive histiocytes and multinucleated giant cells. Immunohistochemical analysis showed that some of the mononuclear cells in the skin were positive for RANKL. After 1 month of Alendronate, an aminobisphosphonate, given at a dosage of 10 mg once a week intravenously for the first 6 weeks and then once a month thereafter, the arthritis and skin nodules improved, and the remission has continued for more than 2 years. The findings in this patient suggest that osteoclast-like multinucleated giant cells differentiate locally in the skin from infiltrating histiocytes with the help of RANKL-positive stromal cells and that alendronate acts directly on cells of monocyte/macrophage lineage in humans. Thus, alendronate should be added to the list of drugs for the treatment of multicentric reticulohistiocytosis.

Calmodulin-like neuronal Ca2+-binding proteins (NCBPs) are expressed primarily in neurons and contain a combination of four functional and nonfunctional EF-hand Ca2+-binding motifs. The guanylate cyclase-activating proteins 1-3 (GCAP1-3), the best characterized subgroup of NCBPs, function in the regulation of transmembrane guanylate cyclases 1-2 (GC1-2). The pairing of GCAPs and GCs in vivo depends on cell expression. Therefore, we investigated the expression of these genes in retina using in situ hybridization and immunocytochemistry. Our results demonstrate that GCAP1, GCAP2, GC1 and GC2 are expressed in human rod and cone photoreceptors, while GCAP3 is expressed exclusively in cones. As a consequence of extensive modification, the GCAP3 gene is not expressed in mouse retina. However, this lack of evolutionary conservation appears to be restricted to only some species as we cloned all three GCAPs from teleost (zebrafish) retina and localized them to rod cells, short single cones (GCAP1-2), and all subtypes of cones (GCAP3). Furthermore, sequence comparisons and evolutionary trace analysis coupled with functional testing of the different GCAPs allowed us to identify the key conserved residues that are critical for GCAP structure and function, and to define class-specific residues for the NCBP subfamilies.

A new bioassay system using an oligodeoxyribonucleotide (DNA) obtained by the in vitro selection method is described. The DNA aptamer which selectively binds to a target molecule, Reactive Green 19 (RG19), was labeled with fluorescein. The circular dichroism spectra revealed that the fluorescein labeling did not significantly affect the conformation of the DNA. The binding affinity toward RG19 of the labeled DNA was the same as that of the nonlabeled DNA. Using the labeled DNA and the RG19-immobilized gel, a semiquantitative assay of RG19 concentration was performed.

Photoreactive insulin was synthesized by coupling with azidobenzoic acid. The insulin derivative was immobilized onto the wells of polystyrene culture plates by photoir-radiation. The photoimmobilized insulin enhanced the growth of anchorage-dependent cells such as Chinese hamster ovary CHO-K1 and mouse fibroblast STO cells by more than native or azidophenyl-derivatized insulin. A small amount of photoimmobilized insulin (1-10% of the amount of the native or derivatized insulin) enhanced the growth of CHO-K1 and STO cells. In addition, the maximal mitogenic effect of the immobilized insulin was greater than that of native or derivatized insulin. Photoimmobilization could be a universal means of immobilizing growth factors onto the surface of materials devoid of chemical functional groups scaffolding growth factors and providing a new protein-free cell culture system or tissue engineering materials.

An anchorage-dependent cell, mouse fibroblast STO cell and an anchorage-independent cell, K562 cell, were cultured on a polymer membrane coimmobilized with insulin and adhesion factors, poly(allylamine), and gelatin. The former is cationic and electrostatically (non-biospecifically) enhances cell adhesion, and the latter is a hydrolyzate of collagen and biospecifically enhances cell adhesion. They were immobilized onto a surface-hydrolyzed poly(methyl methacrylate) membrane by water-soluble carbodiimide. The adhesion of both STO and K562 cells was accelerated by the immobilization of poly(allylamine) or gelatin. The insulin immobilization did not affect adhesion of either cell. Although the growth of STO cells was enhanced on the insulin-immobilized membrane, the growth of K562 cells was not. However, the coimmobilizaiton of insulin and a cell-adhesion factor accelerated growth of both cells. It was considered that an increased frequency of interaction between the immobilized insulin and the receptor led to the cell growth acceleration.

Trypsin was modified with a hydrophobic synthetic polymer, polystyrene. The attachment was achieved by first coupling free amines in the trypsin with azo-bis(4-cyano-valeric acid) and then irradiating the product in the presence of styrene. Decomposition of the azo structure provided free radical initiation of styrene polymerization, with the trypsin thus becoming part of the end group for the polymer chain initiated. That the modified trypsin retained catalytic activity when dissolved in chloroform was demonstrated by using it to catalyze the formation of a peptide linkage between amino acids. The catalytic reaction was stereoselective.

Despite the recent progress in perinatal medicine, it is still difficult to manage the extremely immature newborn. A new extrauterine incubation system has been developed using 14 goat fetuses. The goat fetus is surrounded by artificial amniotic fluid and is connected to an extracorporeal membrane oxygenator. The blood is drained from the umbilical arteries and returned to the umbilical vein. The perfused blood is recirculated and ventilated with a mixture of O2, N2, and CO2 gases to obtain a PO2 of 30-35 mm Hg and a PCO2 of 30-35 mm Hg in the umbilical venous blood. Fetal heart rate, blood pressure, electroencephalogram, and several movement parameters are continuously recorded by the polygraph. With this system, the fetuses can be kept under fairly stable physiological conditions for periods up to 165 h. This improved system might therefore become a useful method to manage the ill fetuses and newborns.