Melanotic oncocytic metaplasia of the nasopharynx: a case report with a focus on immunohistochemical analyses and literature review

Melanotic oncocytic metaplasia (MOM) of the nasopharynx is an extremely rare lesion, with only 21 cases reported in English literature to date. MOM typically occurs near the Eustachian tube opening in Asian men in their 60 s to 70 s. Here, we present a case of MOM in a 57-year-old Japanese man who is a heavy smoker. The patient did not have complaints; MOM was diagnosed incidentally as 4 flat elevated lesions with brown to black discoloration, ranging from 2 to 3 mm in maximal diameter, were found in the right torus tubarius. On suspecting melanoma, the largest lesion was biopsied. Microscopic examination identified both oncocytic metaplasia and melanin pigmentation of the epithelium in the same gland. Upon immunohistochemical examination, melanocytes displayed reactivity for 3 out of 4 melanocytic markers; immunopositivity for S-100 protein, Melan-A, and MITF and immunonegativity for HMB-45 was observed. Normal melanocytes in the nearby surface respiratory epithelium displayed the same pattern of immunoreactivity. Immunopositivity for S-100 protein and immunonegativity for HMB-45 have been previously reported in MOM. Reduction of stimulation of melanocytes in a longstanding lesion like MOM may explain the immunonegativity for HMB-45. S-100 protein, in conjunction with more specific marker for melanocytes, Melan-A or MITF, could prove the definite presence of melanocytes in this case of MOM. As it has been shown by previous reports that MOM pursues a benign course, it will be sufficient to follow up the patients regularly for the remaining 3 lesions.     

ABCC11/MRP8 Expression in the Gastrointestinal Tract and a Novel Role for?Pepsinogen Secretion

ATP-binding cassette (ABC) transporters are involved in chemotherapy resistance. Multidrug-resistance protein 8 (ABCC11/MRP8) is also involved in 5-fluorouracil (5-FU) metabolism. 5-FU and its derivatives are widely used in the treatment of gastrointestinal tract cancers, but little is known about the contribution of ABCC11/MRP8 to gastrointestinal tract and related cancers. Here, we report our investigation of ABCC11/MRP8 expression in normal and cancerous gastrointestinal tract tissues and reveal its novel role in the gastric mucosa. In tissue microarray and surgically resected cancer specimens, immunohistochemical (IHC) staining revealed significantly reduced expression of ABCC11/MRP8 in gastrointestinal tract cancers compared with other cancers. In contrast, strong ABCC11/MRP8 expression was observed in normal gastric mucosa. Additional immuno­fluorescence assays revealed co-localization of ABCC11/MRP8 and pepsinogen I in normal gastric chief cells. Quantitative PCR and Western blot analysis also revealed significant expression of ABCC11/MRP8 in fundic mucosa where the chief cells are mainly located. Furthermore, the ABCC11 mRNA-suppressed NCI-N87 gastric cancer cell line failed to secret pepsinogen I extracellularly. Thus, low expression of ABCC11/MRP8 is consistent with chemotherapeutic regimens using 5-FU and its derivatives in gastrointestinal tract cancers. Our results indicated a novel function of ABCC11/MRP8 in the regulation of pepsinogen I secretion in the normal gastric chief cells.     

Homology modeling in drug discovery: Overview,current applications,and future perspectives

Homology modeling is one of the computational structure prediction methods that are used to determine protein 3D structure from its amino acid sequence. It is considered to be the most accurate of the computational structure prediction methods. It consists of multiple steps that are straightforward and easy to apply. There are many tools and servers that are used for homology modeling. There is no single modeling program or server which is superior in every aspect to others. Since the functionality of the model depends on the quality of the generated protein 3D structure, maximizing the quality of homology modeling is crucial. Homology modeling has many applications in the drug discovery process. Since drugs interact with receptors that consist mainly of proteins, protein 3D structure determination, and thus homology modeling is important in drug discovery. Accordingly, there has been the clarification of protein interactions using 3D structures of proteins that are built with homology modeling. This contributes to the identification of novel drug candidates. Homology modeling plays an important role in making drug discovery faster, easier, cheaper, and more practical. As new modeling methods and combinations are introduced, the scope of its applications widens.     

Value of shear wave velocity measurements for the risk assessment of hepatocellular carcinoma development in patients with nonalcoholic fatty liver disease

Purpose

To evaluate the value of measuring shear wave velocity evoked by acoustic radiation force impulse (VTTQ) for the risk assessment of hepatocellular carcinoma (HCC) development in patients with nonalcoholic fatty liver disease (NAFLD).

Methods

VTTQ was measured three times in each of the four liver segments in 163 NAFLD patients, including 14 HCC cases; the results were statistically evaluated.

Results

The VTTQ was 3.04 ± 0.17 m/s (median ± median absolute deviation) and 1.27 ± 0.25 m/s in patients with and without HCC, respectively, and was significantly higher in HCC cases (p < 0.001). When the patients were classified as F0–F4 based on VTTQ cutoff values, VTTQ was significantly higher in the left lobe than in the right lobe for F0 (p < 0.0001) and for F1 and F2 combined (p < 0.0001), but not significantly higher for F3 and F4 combined (p = 0.070). The robust coefficient of variation was significantly higher in the left than in the right (p = 0.018) and significantly increased as VTTQ increased (p = 0.0002). Multivariate analysis showed that total bilirubin concentration {p = 0.014, 38.9 (2.08–727) [odds ratio (95 % confidence interval)]} and VTTQ [p = 0.006, 113 (3.91–3245)] were the only independent explanatory factors for HCC presence among the seven variables identified by univariate analysis. The area under the receiver-operating characteristic curve in the differentiation of HCC from non-HCC was 0.943 for VTTQ and was comparable to that for other noninvasive markers such as Fib-4 (0.964) or higher than that in BARD (0.838).

Conclusions

These results suggest that fibrosis occurs heterogeneously throughout the liver and that VTTQ measurements are useful in HCC risk evaluation in a NAFLD cohort.     

Acute physiological responses to physiotherapy applications pre and post autologous stem cell transplantation: an experimental study

Objective

We aimed to investigate the acute physiological responses (APR) to physiotherapy applications in patients undergoing autologous stem cell transplantation (ASCT), the difference between pre- and post-ASCT according to APR.

Methods

Twenty-six patients who were hospitalized for ASCT attended regular physiotherapy program. APR was recorded in the beginning and at the end of each exercise session. The differences in APR were calculated for each session. The mean values of the differences in APR were computed in pre-conditioning, pre-, and post-ASCT. Daily complete blood counts were also recorded during ASCT.

Results

Hemoglobin and platelet counts were significantly lower pre- and post-ASCT. Neutrophil counts were significantly lower post-ASCT. The difference in systolic blood pressure (SBP) in the beginning and at the end of the exercise sessions was significantly higher post-ASCT in comparison to pre-ASCT.

Conclusion

There was no significant change in APR except the SBP which suggests that similar level of exercise intensity could be tolerated in pre- and post-ASCT periods as well as preconditioning.