Validity of a newly developed ultraminiature cordless EMG measurement system.

To verify validity of a newly developed ultraminiature EMG measurement system (BMS), the ability of BMS to record masseteric EMG was compared with that of a conventional polygraph system (PG) in the daytime. Effective distance between the transmitter unit and receiver unit of BMS was also examined. Subjects were 12 healthy volunteers. During tapping, maximum clenching, and gum chewing of all subjects, distinct bursts were observed in EMG recorded by BMS as well as PG. RMS values of maximum clenching measured by BMS and PG showed a linear and significant correlation, and there was no significant difference between the data of BMS and PG. When distance between the transmitter unit and receiver unit of BMS was 100 cm or less, no artifact signal was observed. Having obtained these findings suggesting ability for precise measurement in the daytime, we are planning to use BMS in home sleep studies in the next step.     

Chymase participates in chronic dermatitis by inducing eosinophil infiltration

An epicutaneous application of 2,4-dinitrofluorobenzene (DNFB) to a mouse ear caused a transient skin swelling, and the repetition of the challenge enlarged the contact dermatitis. The repeated challenge with DNFB also induced eosinophil infiltration on the application site. Administration of a chymase inhibitor significantly inhibited the ear swelling as well as eosinophil accumulation. An intradermal injection of human chymase to the mouse ear also elicited transient skin swelling and eosinophil infiltration, both of which were augmented in proportion to the number of injections. Human serum albumin and heat-inactivated chymase failed to induce such skin reactions, suggesting the participation of proteolytic activity of the enzyme. In addition, chymase stimulated eosinophil migration in vitro in a concentration-dependent manner. Taken together, these observations suggest that mast cell chymase may contribute to development of the DNFB-induced dermatitis, probably by promoting eosinophil infiltration. It is therefore possible that chymase plays a role in pathogenesis of chronic dermatitis such as atopic dermatitis.     

Expression of collagen, interstitial collagenase, and tissue inhibitor of metalloproteinases-1 in restenosis after carotid endarterectomy.

Extracellular matrix is the principal component of the fibrous caps of atherosclerotic plaques and intimal hyperplastic lesions of reconstructed arteries. Interstitial collagen form an important part of the matrix, and the balance between collagen synthesis and degradation by interstitial collagenase (matrix metalloproteinase-1, MMP-1) may determine whether plaques rupture or vessels develop stenosis. We examined type I procollagen gene expression in human atherosclerotic and restenotic carotid arteries using in situ messenger RNA (mRNA) hybridization and the expression of MMP-1 and its endogenous inhibitor (tissue inhibitor of metalloproteinases-1, TIMP-1) by immunohistochemistry. Compared with normal arteries, atherosclerotic plaques bed increased expression of immunoreactive MMP-1 and TIMP-1 with modest increase of type 1 procollagen mRNA. Early restenotic lesions (< 1.5 years) contained abundant type I procollagen mRNA but little immunoreactive MMP-1 and TIMP-1. Late restenotic lesions (> 4 years) resembled atheroma and exhibited increased immunoreactive MMP-1 and TIMP-1 as well as abundant type I procollagen mRNA. Compared with atherosclerotic plaques, type I procollagen is increased and MMP-1 is decreased in early restenotic lesions. MMP-1 and TIMP-1 expressions are upregulated in lesions with a clear atheroma. These findings suggest that the balance between proteolysis and matrix synthesis may influence both the stability of atheromatous plaques and the development of restenotic lesions.     

Axillary management based on American college of surgeons oncology group Z0011 criteria makes it possible to omit intraoperative diagnosis of sentinel lymph nodes in early breast cancer patients

The ACOSOG Z0011 trial has resulted in the omission of axillary lymph node dissection (ALND) in early breast cancer patients with one or two metastatic sentinel lymph nodes (SLNs). There has been increasing interest in the necessity of intraoperative assessment of SLNs in patients treated based on the Z0011 criteria. We evaluated the utility of intraoperative assessment in these eligible patients. A total of 1396 patients were treated following the Z0011 criteria from April 2012 to December 2019. We examined the proportion and clinicopathological features of patients who underwent ALND due to three or more metastatic SLNs and the sensitivity of intraoperative assessment. Only 16 (1.1%) patients had three or more metastatic SLNs diagnosed by intraoperative assessment, and they immediately underwent ALND. Of the clinicopathological factors, high clinical tumor stage (p = 0.002) and high Ki-67 labeling index value (p = 0.056) were more likely to be associated with the presence of three or more metastatic SLNs. The major independent risk factor for three or more metastatic SLNs was high clinical tumor stage (OR 3.94 [95% CI 1.42–11.0]; p = 0.009). Intraoperative assessment had low sensitivity (70.5%) and a high false-negative rate (29.5%) in detecting SLN metastases. The main finding of our study was the small proportion of patients who required ALND due to three or more metastatic SLNs according to the Z0011 criteria. The Z0011 strategy enables intraoperative assessment of SLNs to be omitted in early breast cancer patients.     

Stroma cells: a novel target of herceptin activity.

PURPOSE: Stroma cells play a relevant role in tumor development and progression. We investigated the activity of herceptin (HER), a humanized monoclonal antibody widely used for the treatment of HER2-overexpressing epithelial cancer, toward stroma cell lines L87/4 and L88/5. EXPERIMENTAL DESIGN: We studied the antiproliferative potential of HER and role of human serum in HER activity. We also investigated the ability of HER to alter ancillary functions of L87/4 and L88/5, such as support to long-term hematopoiesis, growth factor production, breast cancer cell adhesion, and proliferation. RESULTS: Flow cytometry showed that HER2 membrane expression in L87/4 and L88/5 stroma cells was intermediate between the expression in HER2-negative/dim MCF-7 breast cancer cells and HER2-bright SK-BC3 breast cancer cells. HER2 gene amplification was not detected by fluorescence in situ hybridization in either stromal cell lines. HER significantly inhibited L87/4 and L88/5 proliferation. Mean ID(50)s were found to be 2000 and 1700 micro g/ml for L87/4 and L88/5, respectively, after 3-day exposure and 800 micro g/ml for both cell lines after 9-day exposure. The presence of 10% human serum in the culture increased HER inhibitory activity. IC(50) of stroma cells was found to be intermediate between HER2-bright breast cancer cells (SK-BC3) and HER2-negative/dim breast cancer cells (MCF-7). The drug did not significantly affect the ability of stroma cells to support long-term hematopoiesis in the cobblestone area forming cell assay. In contrast, in coculture assay, MCF7 cells demonstrated a worse adhesion and growth capability on HER-treated stroma layers when compared with untreated stroma. Moreover, HER significantly reduced vascular endothelial growth factor production by L88/5 cells. CONCLUSIONS: Our data support the novel finding that HER may have a relevant activity against stroma cells.     

Overexpression of cyclin‐dependent kinase 4 protein in extramammary Paget's disease

Cyclin‐dependent kinase 4 and 6 (CDK4/6) plays an important role in cell cycle progression, and the CDK4/6–cyclin D1 complex controls the cell cycle transition from G₁ phase to S phase. CDK4 is enhanced in several types of cancers and CDK4/6 inhibitors attenuate the proliferation of several types of cancer in vitro/in vivo. The purpose of our study was to investigate the expression pattern of CDK4 and evaluate its clinical importance in extramammary Paget's disease (EMPD). Almost all EMPD tissues were positive for CDK4, and metastatic lesions had a similar immunostaining intensity to primary lesions. In addition, CDK4 protein levels were positively correlated with those of cyclin D1 protein. Taken together, CDK4 may assume a crucial role in EMPD progression.     

Effect of Switching Therapy to Pegaptanib in Eyes With the Persistent Cases of Exudative Age-Related Macular Degeneration

Purpose of this study was to evaluate the efficacy of switching to pegaptanib monotherapy for persistent cases of exudative age-related macular degeneration (AMD).Out of 296 eyes of 296 patients treated with ranibizumab or ranibizumab combined with photodynamic therapy (PDT), 50 eyes of 50 AMD patients were found to be resistant to these treatments. Over a 12-month period, intravitreal pegaptanib (IVP) 0.3 mg was administered at intervals of 6 weeks until the exudation disappeared prospectively. All patients were examined with the following tests: best-corrected visual acuity (BCVA) and central retinal thickness (CRT), determined at the initial visit, before the first IVP (baseline), and at 12 months. The factors responsible for achieving dry macula with IVP were examined statistically.The rate of persistent cases with intravitreal ranibizumab (IVR) and/or PDT was 17.0%. The mean number of IVPs administered was 5.4 (range, 2–9). Logarithm of the minimal angle of resolution BCVA at 12 months was stable or improved by ≥0.3 in 49 eyes (98.0%), with a significant improvement noted between the baseline and final BCVA (P = 0.01, paired t test). The CRT (mean ± standard deviation) was 446.9 ± 150.6 µm at the initial visit, 414.5 ± 146.5 µm at baseline, and 318.7 ± 99.0 µm at 12 months. There was a significant decrease in the mean CRT between the measurements at baseline and at 12 months after the first IVP (P = 0.002, Bonferroni correction). At 12 months, the exudative change was completely resolved in 27 eyes (54.0%) and reduced in 21 eyes (42.0%). The number of previous IVR treatments was significantly correlated with dry macula at 12 months.After switching therapy to pegaptanib in persistent cases of AMD, most patients maintained or improved their BCVA and exhibited a positive treatment response at 12 months.     

Cellular expression of CD markers in immune thrombocytopenic purpura: implications for prognosis

Immune thrombocytopenic purpura (ITP) is an autoimmune bleeding disorder associated with platelet destruction. Abnormalities in frequency and function of different immune cells can play a crucial role in this disease. The aim of this study was to evaluate the prognostic value of CD markers’ expressions by immune cells in ITP. Peripheral blood samples were collected from 25 ITP patients before and after treatment. The expression of CD markers was evaluated by flow cytometry technique. The expression of CD38 and CD56 was significantly lower before treatment than after it (p = 0.025 and p = 0.036, respectively). Furthermore, a positive correlation was found between CD38 expression with platelet count before (r = 0.496, p = 0.012) and after treatment (r = 0.404, p = 0.045). No significant relationship was found between this marker and platelet count while CD4 expression was higher before treatment than after it (p = 0.002). In conclusion, CD38 may have independent prognostic value in ITP and we suggest that it can be a prognostic marker for this disease.     

Enamel remineralization effect of a dentifrice containing calcium sodium phosphosilicate: an optical coherence tomography observation

Objective: The purpose of this study was to examine the effects of a dentifrice containing 5% calcium sodium phosphosilicate (CSP) on the remineralization of the enamel using optical coherence tomography (OCT).

Materials and methods: Bovine incisors were sliced and shaped in a rectangular form. One group of five specimens was treated with undersaturated 0.1 M lactic acid buffer solution (pH 4.75) for 10?min and then placed in artificial saliva (pH 7.0) (De group). Other specimens were stored in solutions of toothpaste containing CSP for 10?min, followed by 10-min immersion in the lactic acid buffer solution twice a day before storage in artificial saliva (CSP group). An additional group was stored in only artificial saliva (control group). OCT imaging on the selected location of the enamel surface was performed. The peak intensity and width at 1/e² were recorded in each of the six areas on the sample and averaged, and the sample size of each group was six. The integrated value in units (dB?×?μm) was calculated in the area of peak intensity. The data for each group was subjected to one-way repeated-measures ANOVA and Tukey HSD tests (α?=?0.05).

Results: The changes in integrated values of each group were different. A slight but significant increase in the integrated value was observed in the control group, whereas a slight but significant decrease in the value was observed the De group. Integrated values increased in the CSP group.

Conclusions: Remineralization occurred upon immersion in the toothpaste containing CSP.