Olfaction after endoscopic surgery for sellar and parasellar disease: an updated systematic review and meta-analysis.

BACKGROUND: Whether endoscopic surgery for sellar/parasellar disease causes significant deficits in olfactory function remains unclear. We aimed to systematically review the olfactory outcomes in such settings based on the evidence up to date. METHODS: PubMed, EMBASE, and CENTRAL were searched through February 1, 2021. Included studies were limited to endoscopic surgery for sellar/parasellar disease with follow-up olfactory function measured by standardized olfactory testing methods or subjective assessment. The primary outcome was the change in olfactory function after surgery assessed by standardized olfactory testing methods. The secondary outcome was the change in subjective olfactory function. Random-effects model was used in obtaining combine effects. Study quality was assessed using the Newcastleâ€"Ottawa scale. Sensitivity analysis was carried out using the leave-one-out approach, and publication bias was assessed using Egger's test. RESULTS: The results show no significant difference in olfaction assessed by standardized olfactory testing methods at 1-3 months post-surgery (880 patients in 16 studies) or at 6-12 months post-surgery (1320 patients in 16 studies) compared to pre-surgery, whereas a significantly lower subjective olfaction at 3 months was observed. In addition, the lack of significant change in olfaction as assessed by standardized olfactory testing methods was observed regardless of whether patients were treated with or without the nasoseptal flap (NSF) harvesting. Heterogeneity and publication bias were observed, whereas sensitivity analysis showed the meta-analysis results are robust. CONCLUSION: The findings of this updated systematic review and meta-analysis support the conclusion that endoscopic surgery for sellar and parasellar pathology may pose no greater risk of olfactory dysfunction. In addition, the current evidence does not support there is an increased risk of diminished olfaction among patients treated with NSF during surgery.

Ontogeny of human IgE-expressing B cells and plasma cells.

BACKGROUND: IgE-expressing (IgE+ ) plasma cells (PCs) provide a continuous source of allergen-specific IgE that is central to allergic responses. The extreme sparsity of IgE+ cells in vivo has confined their study almost entirely to mouse models. OBJECTIVE: To characterize the development pathway of human IgE+ PCs and to determine the ontogeny of human IgE+ PCs. METHODS: To generate human IgE+ cells, we cultured tonsil B cells with IL-4 and anti-CD40. Using FACS and RT-PCR, we examined the phenotype of generated IgE+ cells, the capacity of tonsil B-cell subsets to generate IgE+ PCs and the class switching pathways involved. RESULTS: We have identified three phenotypic stages of IgE+ PC development pathway, namely (i) IgE+ germinal centre (GC)-like B cells, (ii) IgE+ PC-like 'plasmablasts' and (iii) IgE+ PCs. The same phenotypic stages were also observed for IgG1+ cells. Total tonsil B cells give rise to IgE+ PCs by direct and sequential switching, whereas the isolated GC B-cell fraction, the main source of IgE+ PCs, generates IgE+ PCs by sequential switching. PC differentiation of IgE+ cells is accompanied by the down-regulation of surface expression of the short form of membrane IgE (mIgES ), which is homologous to mouse mIgE, and the up-regulation of the long form of mIgE (mIgEL ), which is associated with an enhanced B-cell survival and expressed in humans, but not in mice. CONCLUSION: Generation of IgE+ PCs from tonsil GC B cells occurs mainly via sequential switching from IgG. The mIgEL /mIgES ratio may be implicated in survival of IgE+ B cells during PC differentiation and allergic disease.

Simultaneous induction of apoptosis and necroptosis by Tanshinone IIA in human hepatocellular carcinoma HepG2 cells.

Tanshinone IIA (Tan IIA), a constituent of the traditional medicinal plant Salvia miltiorrhiza BUNGE, has been reported to possess anticancer activity through induction of apoptosis in many cancer cells. Surprisingly, the present study finds that Tan IIA simultaneously causes apoptosis and necroptosis in human hepatocellular carcinoma HepG2 cells. We further find that apoptosis can be converted to necroptosis by pan-caspase inhibitor Z-VAD-fmk, and the two death modes can be blocked by necroptotic inhibitor necrostatin-1. The underlying mechanisms are revealed by analysis of the signaling molecules using western blotting. In control cells, FLICE inhibitory protein in short form (FLIPS) is expressed in relatively high levels and binds to caspase 8 in ripoptosome, which supposedly sustains cell survival. However, in Tan IIA-treated cells, FLIPS is down-regulated and may thus cause homodimer formation of cleaved caspase 8, cleavage of receptor-interacting serine/threonine-protein kinases 1, 3 (RIP1, RIP3), and mixed-lineage kinase domain-like (MLKL), in turn leads to cell apoptosis. In parallel, Tan IIA causes necroptosis by forming a suggested necrosomal complex composed of RIP1/RIP3. Regarding the inhibitors, z-VAD-fmk diminishes the cleaved caspase 8, RIP1, RIP3, and MLKL induced by Tan IIA, and reconstructs the ripoptosome complex, which marks cells moving from apoptosis to necroptosis. Nec-1 recovers the Tan IIA down-regulated FLIPS, consequently causes FLIPS to form heterodimer with caspase 8 and thus block apoptosis. Meanwhile, cleaved forms of RIP1 and RIP3 were observed preventing necroptosis. Intriguingly, the cytotoxicity of tumor necrosis factor-related apoptosis-inducing ligand to HepG2 cells is enhanced by Tan IIA in a pilot study, which may be attributed to low FLIPS levels induced by Tan IIA. In short, Tan IIA simultaneously induces both Nec-1 inhibition and FLIPS regulation-mediated apoptosis/necroptosis, which has not been previously documented. Moreover, the involvement of the cleavage type of MLKL in executing necroptosis warrants further investigation.

Generating allergen-specific human IgEs for immunoassays by employing human ε gene knockin mice.

BACKGROUND: Antigen-specific human IgEs are important reagents in immunoassays to quantify antigen-specific IgEs in allergic patients, but they are not easy to prepare. METHODS: We constructed a knockin homozygous mouse strain, referred to as HεκKI strain, whose gene segment encoding γ1 constant region has been replaced by that encoding human ε constant region and gene segment encoding κ constant region replaced by that encoding human κ constant region. The mice were tested for their ability to produce antigen-specific chimeric human IgE (with mouse variable regions) upon the immunization with ovalbumin and papain. Subsequently, the spleen cells from the immunized mice were used as the source of B cells for the preparation of hybridomas, which secreted monoclonal human IgE antibodies specific for the antigens. RESULTS: The HεκKI mice expressed human IgE (ε, κ) in serum at levels 10- to 30-fold higher than those of mouse IgE. Upon immunization with an antigen, the mice yielded splenic B cells for preparing hybridomas that secrete chimeric human IgE specific for the antigen. Purified IgEs from those hybridomas could activate a basophilic cell line to undergo degranulation upon the stimulation with their respective antigens. CONCLUSIONS: We have developed a human ε gene and κ gene knockin mouse strain, which is useful for producing various antigen-specific chimeric human IgEs for potential use as standards in immunoassays.

Prognostic significance of triple negative breast cancer at tumor size 1 cm and smaller.

AIMS: The purpose of this study was to clarify the prognostic significance of triple-negative breast cancer (TNBC) with a tumor size ≤ 1 cm. MATERIALS AND METHODS: Patients with primary operable breast cancer with a tumor size ≤ 1 cm were enrolled at Changhua Christian Hospital and National Cheng-Kung University Hospital. Tumors negative for ER, PR, and HER-2 were classified as TNBCs and compared with tumors with any receptor positivity (non-TNBC) for disease-free survival (DFS) and cancer-specific survival (CSS). RESULTS: From 1995 to 2006, a total of 377 patients with tumor size ≤ 1 cm were enrolled. Compared with non-TNBC patients, TNBC patients with a tumor size ≤ 1 cm as a whole or in a lymph node-positive subgroup were not associated with a poorer 5-year DFS and CSS. In lymph node-negative patients (pT1a-bN0M0), TNBC was associated with a poorer 5-year CSS but not DFS. Compared with the hormone receptor-positive, HER-2-negative subgroup, TNBC was associated with poorer DFS and CSS. In the multivariate Cox regression hazard analysis, lymph node invasion was the most important cause of disease recurrence and cancer-specific death. CONCLUSION: TNBC is very likely an independent risk factor in small (≤1 cm) node-negative invasive breast cancer. With tumors 1 cm and smaller, lymph node invasion was the single most important prognostic factor.

A retrospective study of catastrophic invasive fungal infections in patients with systemic lupus erythematosus from southern Taiwan.

As very few large scale publications of invasive fungal infection (IFI) have been reported in lupus patients from individual medical centers, a retrospective study was performed from 1988 to 2009 in southern Taiwan. Demographic characteristics, clinical and laboratory data, and mycological examinations were analyzed. Twenty cases with IFI were identified in 2397 patients (0.83% incidence). There were 19 females and one male with an average age of 31.8 +/- 12.6. Involved sites included eight disseminated cases, six central nervous system, four lungs, one abdomen and one soft tissue. IFI contributed to a high mortality with 10 deaths (50%), and there were no survivors for the disseminated cases and Candida-infected patients. High activity (Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) > 8) was noted in 50% of IFI episodes. The survival from IFI diagnosis to death was only 7.7 +/- 4.2 days, all in a rapid course. No statistical difference was found between survivors and non-survivors when comparing their SLEDAI. Eighty-five percent of IFI episodes under high dosages of corticosteroids therapy and 95% of patients had lupus nephritis. There was an increased risk of IFI in the lupus patients receiving high daily dosage of prednisolone therapy. Critical information from analyses of the present large series could be applied into clinical practices to reduce the morbidity and mortality in such patients.

Immunohistochemical expression of GCIP in breast carcinoma: relationship with tumour grade, disease-free survival, mucinous differentiation and response to chemotherapy.

AIMS: Grap2 and cyclin-D interacting protein (GCIP) is a putative tumour suppressor in human cancer. The aim was to investigate its prognostic significance in human breast carcinoma. METHODS AND RESULTS: Immunohistochemical analysis of breast carcinoma specimens from 107 female patients was performed. Decreased cytoplasmic expression of GCIP was detected in breast carcinomas compared with normal ductal epithelium (P < 0.001). Higher GCIP scores were observed in patients with lower histological grade, mucinous carcinomas and better clinical outcome (P < 0.05). Disease-free survival was significantly longer in patients with high GCIP scores than in those with low GCIP scores (P = 0.010). However, GCIP expression was independent of the status of oestrogen receptor, progesterone receptor, Her-2/neu and cancer stage. Moreover, in patients receiving neoadjuvant chemotherapy, those with higher GCIP scores showed potentially more reduction of tumour size compared with those with lower GCIP scores (borderline significance, P = 0.053). CONCLUSIONS: The current data provide evidence that decreased expression of GCIP in vivo is present in human breast carcinoma and indicate that GCIP is a potential indicator of good prognosis. In patients receiving neoadjuvant chemotherapy, it may also have predictive value for the chemotherapeutic response.

Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells.

The ribosomal acidic P0 protein, an essential component of the eukaryotic ribosomal stalk, was found to interact with the helix-loop-helix protein human Grap2 and cyclin D interacting protein (GCIP)/D-type cyclin-interacting protein 1/human homolog of MAID protein. Using in vivo and in vitro binding assays, we show that P0 can interact with the N and C termini of GCIP via its N-terminal 39-114 amino-acid residues. Although the P0-GCIP complex was detected mainly in cytoplasmic fraction, polysome profile analysis indicated that the P0-GCIP complex did not coelute with either polysomes or 60S ribosomes, suggesting that GCIP associates with the free form of P0 in the cytoplasm. Transfection of GCIP into MCF-7 cells resulted in decreased levels of pRb phosphorylation. Cotransfection of P0 with GCIP, however, resulted in GCIP-mediated reduction of pRb phosphorylation level which was repressed by P0. Furthermore, overexpression of P0 in breast cancer and hepatocellular cancer cell lines promoted cell growth and colony formation compared to control transfectants. Overexpression of P0 also increased cyclin D1 expression and phosphorylation of pRb at Ser780. Interestingly, P0 mRNA was overexpressed in 12 of 20 pairs of breast cancer/ normal breast specimens (60%). Together, these data indicate that P0 overexpression may cause tumorigenesis in breast and liver tissues at least in part by inhibiting GCIP-mediated tumor suppression.

Benign mucocele-like lesion of the breast: how to differentiate from mucinous carcinoma before surgery.

The aim of the study was to improve the pre-operative diagnosis of mammary mucinous lesions. All mucinous lesions detected by fine needle aspiration (FNA) and confirmed by histological examination were reviewed by cytological findings, mammographic appearances and sonographic findings. Twenty aspirates had corresponding pathology, including 12 mucinous carcinomas, two mucocele-like lesions (MLL) with atypical ductal hyperplasia, three MLL with ductal hyperplasia and three simple MLL. Simple MLL and mucocele-like with ductal hyperplasia showed scant cellularity, no or rare intact single tumour cells, monolayered arrangement and absence of nuclear atypia. In contrast, most mucinous carcinomas showed higher cellularity, more single tumour cells, three-dimensional clusters, and mild to marked nuclear atypia. However, MLL with atypical ductal hyperplasia showed cytological features overlapping with mucinous carcinoma. MLL had a non-specific mammographic appearance and showed a cystic lesion on sonography. Mucinous carcinoma appeared as a solid mass on sonography and as a distinct nodule on mammography. Based on the combination of FNA cytology and image findings, benign MLL can be correctly distinguished from mucinous carcinoma before surgery.

Assessment of sorbent/water ratio effect on adsorption using dimensional analysis and batch experiments.

Many factors affect adsorption phenomena in solid-liquid systems. One of the most important factors is the sorbent/water (S/W) ratio in the system. However, the effect of varying S/W ratios on the adsorption is still unclear. In this study, batch experiments were examined to observe the adsorption of four contaminants (copper, cadmium, Butachlor, and Deltamethrin) in six soils with texture ranging from silty clay to loamy sand and with different S/W ratios. Dimensional analysis was used to assess the relationship between adsorption phenomena and S/W ratio. We have assumed that the total amount of sorbate sorbed in soil is a function of the equilibrium concentration, the volume of sorbate solution, and the sorbent amount in the system. A power function (Freundlich-like) model was obtained from the dimensional analysis. It can describe precisely the adsorption phenomena of different sorbents and sorbates in the moisture regime of paddy soils. Therefore, proper adsorption parameters can be obtained by this power function model regardless of the solids effect, which can then be utilized to describe the fate of solute in soil using solute transport models.

Preparing a human membrane and secreted protein-enriched cDNA library using PCR primers derived from a genomic database.

We describe here a strategy for preparing a human membrane and secreted protein (MSP)-enriched cDNA library based on human MSP- and non-MSP-encoding cDNA sequences in the databases. The signal peptide parts of the MSP-encoding cDNA sequences, which currently comprise about half of the estimated total number in humans, were analyzed for common patterns. These patterns form a 'minimal' set of polymerase chain reaction primer candidates of length varying from 9 to 21 nt. The products stemming from each primer candidate were determined and the results allowed us to obtain an 'optimal' mixed-length primer set. Ninety-six percent of the primers in this set were predicted to yield

Expression in Pichia pastoris and characterization by circular dichroism and NMR of rhodostomin.

Rhodostomin (Rho) is a snake venom protein isolated from Calloselasma rhodostoma. Rho is a disintegrin that inhibits platelet aggregation by blocking the binding of fibrinogen to the integrin alpha(IIb)beta3 of platelets. Rho produced in Escherichia coli inhibited platelet aggregation with a K(I) value of 263 nM. Although functional, Rho produced in E. coli is misfolded based on our 2D and 3D NMR studies. In order to correct the folding problem, Rho was expressed in Pichia pastoris. The recombinant Rho expressed in P. pastoris inhibited platelet aggregation with a resulting K(I) value of 70 nM. This is the same potency as that of native Rho. CD analysis showed that the secondary structures of Rho are pH-independent and contain 3.5-7.9% alpha-helix, 48.2-50.5% beta-structures, and 42.3-47% coil. The sequential assignment and structure analysis of Rho were obtained using 2D and 3D 15N-edited NMR spectra. These results provide the first direct evidence that highly disulfide-bonded disintegrin can be expressed in P. pastoris with the correct fold. This evidence may serve as the basis for exploring the structure and function relationships as well as the dynamics of disintegrin and its variants.

Transport modeling of copper and cadmium with linear and nonlinear retardation factors.

The predictive accuracy of using the one-dimensional advection-dispersion equation to evaluate the fate and transport of solute in a soil column is usually dependent on the proper determination of chemical retardation factors. Typically, the distribution coefficient (Kd) obtained by fitting the linear sorption isotherm has been extensively used to consider general geochemical reactions on solute transport in a low-concentration range. However, the linear distribution coefficient cannot be adequately utilized to describe the solute fate at a higher concentration level. This study employed the nonlinear equilibrium-controlled sorption parameters to determine the retardation factor used in column leaching experiments. Copper and cadmium transportation in a lateritic silty-clay soil column was examined. Through the explicit finite-difference calculations with a third-order total-variation-diminishing (TVD) numerical solution scheme, all results of the theoretical copper and cadmium breakthrough curves (BTCs) simulated by using the Freundlich nonlinear retardation factors revealed good agreement with the experimental observations.

Determination of transdermal sildenafil in nude mouse skin by reversed-phase high-performance liquid chromatography.

A simple and sensitive high-performance liquid chromatographic method was developed for the determination of sildenafil transdermal permeation of nude mouse skin. A reversed-phase column with UV detection at 224 nm was used for chromatographic separation. The mobile phase consisted of 32% acetonitrile with 0.2% phosphoric acid in water at pH 5.3 adjusted with 10 M NaOH with the flow-rate set at 1.0 ml/min. The limit of quantitation achieved was 5 ng/ml, and the calibration curve showed good linearity over the concentration range of 5-500 ng/ml. The relative standard deviations of within- and between-day analyses were all within 15%. Sildenafil was found to be stable between pH 3 and 12 during 24-h incubation with skin. After transdermal administration of 15.8 microg/ml of sildenafil to nude mouse skin, it was detected as early as 15 min. The transport amount of sildenafil could be quantitated and, at pH 8-11, had the highest permeation rate in nude mouse skin.

The pharmacological basis of anti-IgE therapy.

The treatment of asthma and allergic rhinitis using unique, humanized anti-IgE monoclonal antibodies with very particular binding specificities is now supported by the results of multiple phase II and III human clinical studies. The therapeutic efficacy of this approach is attributable to several pharmacological mechanisms. In addition to the expected effects of these monoclonal antibodies in neutralizing free IgE and inhibiting IgE production by B cells, several indirect biochemical and cellular effects have been uncovered during the course of the clinical trials. These include the accumulation of potentially beneficial IgE-anti-IgE immune complexes and the downregulation of the high-affinity IgE Fc receptors (FcvarepsilonRI) on basophils and mast cells. This article analyzes the structural basis of the specificity of the anti-IgE antibodies and pertinent results from in vitro experiments, animal model studies, and human clinical trials in an attempt to provide a cogent pharmacological interpretation of the therapeutic effects of anti-IgE therapy in both the near- and long term. The development of anti-IgE therapy over the past 10 years provides an interesting example of the emergence of a conceptually new, biotechnology-produced pharmaceutical.

Immunolocalization of BRCA1 protein in normal breast tissue and sporadic invasive ductal carcinomas: a correlation with other biological parameters.

AIM: BRCA1, a nuclear phosphoprotein, normally functions as a negative regulator of the cell cycle and may be an active inhibitor of neoplastic progression. Mutation of the BRCA1 gene has been demonstrated in 80% of familial breast cancer. Decreased mRNA levels or aberrant subcellular locations of BRCA1 have been identified in breast cancer lines and in sporadic cases of breast cancer tissues. The expression of BRCA1 in large series of variously differentiated breast carcinomas with correlation with other biological parameters has not been clarified. METHODS AND RESULTS: The BRCA1 expression in normal breast tissue (n = 15) and in sporadic cases of invasive ductal carcinoma (n=108) was determined using immunohistochemistry. BRCA1 expression was correlated with other prognostic parameters including p53, c-erbB-2, bcl-2, oestrogen receptor (ER), histological grade, tumour size, axillary lymph node status and age. BRCA1 was exclusively (100%) localized in the nuclei of normal ductal and lobular epithelia. However, this nuclear expression pattern was variable in breast carcinoma (76.8%). Loss of nuclear BRCA1 expression (22 of 108 cases, 20.4%) correlated well with high histological grade (P<0.025) and bcl-2-negative tumours (P<0.05) and frequently in ER-negative tumours. CONCLUSION: BRCA1 nuclear expression could be considered to represent the normal or physiological phenotype. Complete loss of BRCA1 nuclear expression in breast cancer and its correlation with other poor prognostic markers suggest that BRCA1 expression may play an important role in the pathogenesis and prognosis of sporadic breast carcinoma. Altered BRCA1 phenotype may therefore provide an additional prognostic parameter for breast cancer.

Diagnosing invasive cystic hypersecretory duct carcinoma of the breast with fine needle aspiration cytology. A case report.

BACKGROUND: Cystic hypersecretory duct carcinoma (CHC) of the breast, first described in 1984, is a rare variant of duct carcinoma. Histologically it is characterized by the formation of dilated ducts and cysts containing an eosinophilic secretory product resembling thyroid colloid. The lining epithelium of the cysts atypically proliferates to form intraductal carcinoma. Only four cases of invasive cystic hypersecretory carcinoma have been reported. CASE: We present a case of invasive CHC with tumor emboli in many lymphatic spaces and axillary nodal metastases. The lesion was also evaluated by fine needle aspiration. Direct smears with Papanicolaou stain were highly cellular and had abundant, intensely staining, orange-to-gray-green thyroid colloid-like material. Epithelial cells, showing a variety of cellular patterns, were indistinguishable from usual ductal carcinoma cells. These cytologic findings may be characteristic enough to suggest cystic hypersecretory carcinoma. CONCLUSION: The cytologic features of CHC are distinctive and correlate with histology. This was the first presentation of colloidlike secretory material in cytologic material with Papanicolaou stain in such a case. Invasive CHC tends to have aggressive behavior. Cystic hypersecretory hyperplasia coexisted in this case.

Extended latissimus dorsi musculocutaneous flap for breast reconstruction: experience in Oriental patients.

Unilateral breast reconstruction with an extended latissimus dorsi musculocutaneous flap was carried out for 12 women in the National Cheng Kung University Hospital. Eleven patients acquired a good or fair result cosmetically. We analysed the net weight of the flap as well as various anthropometric data to see what effect they have on the final aesthetic outcome. The weight of the flap ranged from 180 to 610 g, and the resected specimen weighed from 160 to 635 g. The flap weight was equivalent to 61%-113% of the specimen weight. A satisfactory result could be achieved when the bulk of the flap attained 70% of the mass resected. We also observed that the aesthetic quality is better when the breast is less ptotic. All of the muscle transfers survived completely without any flap loss. The only complications included one minor wound edge slough and another modest seroma formation at the donor site. This reconstructive method is a viable option for young women with small or medium-sized breasts who anticipate pregnancy in the future. It is especially advisable in Oriental society, since the breast size of the patients is generally smaller and the donor scar is hidden, given the hypertrophic tendency of the lower abdominal scar in Asian people undergoing TRAM flap reconstruction.