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The upper gastrointestinal tract consists of oesophagus, stomach, and duodenum. These are distinct from one another histologically. The lining of the oesophagus consists mainly of non-keratinising stratified squamous epithelium, and there is a variable amount of columnar epithelium distally. The stomach has three main histological regions, which from proximal to distal are the cardia, the body/fundus, and the antrum. All of these regions include surface epithelial cells that extend downwards into foveolae. Beneath the foveolae are a short isthmic zone and a deeper glandular layer. In the body/fundus, the glandular layer is thicker and the glands are more closely packed than in the antrum. Parietal cells and chief cells are the main component of the body/fundus glands while in the antrum they are sparse. The gastric cardia is a short segment that usually lacks parietal and chief cells. In the normal state, columnar mucosa extends from the stomach upwards into the distal oesophagus for a variable length. In contrast, Barrett’s oesophagus is pathological replacement of the distal oesophageal mucosa by metaplastic columnar mucosa that may be gastric or intestinal. The duodenal mucosa includes villi and crypts, both lined by columnar absorptive cells. Other epithelial cell types include goblet cells and Paneth cells. Endocrine cells are present at all sites but are difficult to identify and sparse in the oesophagus.
Advances in immunohistochemistry have spearheaded major developments in our understanding and classification of sinonasal tumours. In the last decade, several new distinct histopathological entities of sinonasal cancer have been characterised.
This review aims to provide a clinical update of the major emerging subtypes for the ENT surgeon and an overview of the management strategies available for this heterogeneous group of pathologies.
Although rare, knowledge of sinonasal neoplasm subtypes has implications for prognosis, treatment strategies and the development of novel therapeutic targets.
Most commonly described as sporadic, pulmonary adenocarcinoma with enteric differentiation (PAED) is a rare variant of invasive lung cancer recently established and recognised by the World Health Organization. This tumour is highly heterogeneous and shares several morphological features with pulmonary and colorectal adenocarcinomas. Our objective is to summarise current research on PAED, focusing on its immunohistochemical and molecular features as potential tools for differential diagnosis from colorectal cancer, as well as prognosis definition and therapeutic choice. PAED exhibits an ‘entero-like’ pathological morphology in more than half cases, expressing at least one of the typical immunohistochemical markers of enteric differentiation, namely CDX2, CK20 or MUC2. For this reason, this malignancy appears often indistinguishable from a colorectal cancer metastasis, making the differential diagnosis laborious. Although standard diagnostic criteria have not been established yet, in the past few years, a number of approaches have been addressed, aimed at defining specific immunohistochemical and molecular signatures. Based on previously published literature, we have collected and analysed molecular and immunohistochemical data on this rare neoplasm, and have described the state of the art on diagnostic criteria as well as major clinical and therapeutic implications.
The analysis of data from 295 patients from 58 published articles allowed us to identify the most represented immunohistochemical and molecular markers, as well as major differences between Asian PAEDs and those diagnosed in European/North American countries. The innovative molecular approaches, exploring driver mutations or new gene alterations, could help to identify rare prognostic factors and guide future tailored therapeutic approaches to this rare neoplasm.
In Pakistan, oral cancer ranks as the most common malignancy in males and the second most common malignancy in females. Cyclooxygenase-2 has been explored as an agent of carcinogenesis in oral and other neoplasms. This study aimed to observe the expression of cyclooxygenase-2 in oral squamous cell carcinoma, and to correlate the expression with patients’ clinical features and overall and disease-free survival.
Immunohistochemistry for cyclooxygenase-2 was performed on a total of 100 oral squamous cell carcinoma formalin-fixed, paraffin-embedded blocks. Expression was correlated with patients’ clinicopathological variables and overall and disease-free survival.
Cyclooxygenase-2 was overexpressed in 55 per cent of oral squamous cell carcinoma patients. Overexpression was correlated with overall survival (p = 0.013) and disease-free survival (p = 0.001) on univariate analysis. However, on multivariate analysis, cyclooxygenase-2 was associated with only disease-free survival (p = 0.044) and not overall survival (p = 0.208).
Expression of cyclooxygenase-2 is associated with poorer overall survival and higher rates of recurrence in oral squamous cell carcinoma patients.
Significant experimental evidence supports fat as a taste modality; however, the associated peripheral mechanisms are not well established. Several candidate taste receptors have been identified, but their expression pattern and potential functions in human fungiform papillae remain unknown. The aim of this study is to identify the fat taste candidate receptors and ion channels that were expressed in human fungiform taste buds and their association with oral sensory of fatty acids. For the expression analysis, quantitative RT-PCR (qRT-PCR) from RNA extracted from human fungiform papillae samples was used to determine the expression of candidate fatty acid receptors and ion channels. Western blotting analysis was used to confirm the presence of the proteins in fungiform papillae. Immunohistochemistry analysis was used to localise the expressed receptors or ion channels in the taste buds of fungiform papillae. The correlation study was analysed between the expression level of the expressed fat taste receptors or ion channels indicated by qRT-PCR and fat taste threshold, liking of fatty food and fat intake. As a result, qRT-PCR and western blotting indicated that mRNA and protein of CD36, FFAR4, FFAR2, GPR84 and delayed rectifying K+ channels are expressed in human fungiform taste buds. The expression level of CD36 was associated with the liking difference score (R −0·567, β=−0·04, P=0·04) between high-fat and low-fat food and FFAR2 was associated with total fat intake (ρ=−0·535, β=−0·01, P=0·003) and saturated fat intake (ρ=−0·641, β=−0·02, P=0·008).
Tularemia caused by the bacterium Francisella tularensis is a zoonotic disease. Tularemia is a common disease in the hare, and as a game species can be an important source of infection for humans. In this study, hares diagnosed with tularemia were examined with the aim to investigate whether the muscle (meat) had any pathological changes and/or contained F. tularensis. Real-time PCR and/or immunohistochemistry (IHC) detected the bacteria in muscle samples from 40 out of 43 investigated hares. IHC showed that bacteria were few and most commonly located in the peri- and endomysium. Histopathology showed occasional perimysial necroses and mild inflammation in association to the bacteria. Attempts to culture from 14 muscle samples were successful in two cases, both stored in the freezer <1 year. The result of this study shows that since F. tularensis is present in the muscle of infected hares, there is a risk for human infection when consuming undercooked hare meat. The risk is enhanced by the fact that some hares do not have easily detected gross lesions. The study contributes to a better understanding of sources of infection and risk factors for humans to contract tularemia.
Scabies is a parasitic disease caused by the ectoparasite Sarcoptes scabiei, affecting different mammalian species, including rabbits, worldwide. In the present study, we cloned and expressed a novel inorganic pyrophosphatase, Ssc-PYP-1, from S. scabiei var. cuniculi. Immunofluorescence staining showed that native Ssc-PYP-1 was localized in the tegument around the mouthparts and the entire legs, as well as in the cuticle of the mites. Interestingly, obvious staining was also observed on the fecal pellets of mites and in the integument of the mites. Based on its good immunoreactivity, an indirect enzyme-linked immunosorbent assay (ELISA) using recombinant Ssc-PYP-1 (rSsc-PYP-1) as the capture antigen was developed to diagnose sarcoptic mange in naturally infected rabbits; the assay had a sensitivity of 92·0% and specificity of 93·6%. Finally, using the rSsc-PYP-1-ELISA, the Ssc-PYP-1 antibody from 10 experimentally infected rabbits could be detected from 1 week post-infection. This is the first report of S. scabiei inorganic pyrophosphatase and the protein could serve as a potential serodiagnostic candidate for sarcoptic mange in rabbits.
The growing request for healthier fatty acid composition of animal products is raising the necessity of a deeper knowledge of the main factors controlling fatty acids storage in muscle and backfat. Perilipin (PLIN) 5, and the whole Perilipin family, seem to play a crucial role in the regulation of lipids deposition as code for proteins coating intracellular lipid droplets surface. Nevertheless, the knowledge of these genes in pig is still incomplete. The present research was aimed at investigating in different pig breeds the PLIN5 gene, analysing its expression level and the associations of the variability in its downstream gene region with pork meat and carcass quality traits. Moreover, the PLIN5 protein localisation in porcine skeletal muscle was investigated through immunofluorescence, resulting to be widespread in Semimembranosus muscle (SM) myofibers. The identified single nucleotide polymorphism (SNP) rs327694326 (NC_010444.4:g.74314701T>C) located in PLIN5 downstream region was analysed in different pig populations, represented by 512 Italian Large White (ILW) pigs, 300 Italian Duroc (IDU) samples, 100 Italian Landrace, 100 Pietrain and 60 pigs belonging to three Italian native breeds (20 samples of Cinta Senese, 20 Calabrese and 20 Casertana pigs). The C allele was found in ILW, IDU and Pietrain pigs. In ILW pigs this SNP showed results indicating a possible association with oleic and cis-vaccenic fatty acid contents in backfat tissue. Furthermore, as PLINs are known to regulate lipases activity, we tested if the rs327694326 SNP was associated with differences in Hormone-sensitive lipase (LIPE) gene expression levels. In SM of ILW pigs, PLIN5 C allele was associated with significantly lower LIPE transcription levels than T allele (P=0.02 for Student’s t test of TT v. CT samples, P<0.0001 for TT v. CC pigs), whereas in IDU breed no significant difference was noticed in LIPE transcription levels between TT and TC animals. The results may suggest that variations in the PLIN5 sequence may be linked to LIPE expression through a still poorly known regulative molecular process.
The present study characterized the biological function of the asparaginyl peptidase legumain-1 (LEG-1) of the bovine lungworm Dictyocaulus viviparus and its suitability as a recombinant vaccine against dictyocaulosis. Quantitative real-time PCR and immunoblot analysis revealed LEG-1 to be almost exclusively transcribed and expressed in parasitic lungworm stages. Immunohistochemistry localized the enzyme in the parasite's gut, which was confirmed by immunoblots detecting LEG-1 in the gut as well as male testes. LEG-1 was recombinantly (rLEG-1) expressed in the yeast Pichia pastoris and subsequently analysed in activity assays for its enzyme functions and substrate specificity. For sufficient functionality, rLEG-1 needed trans-activation through D. viviparus cathepsin L-2, indicating a novel mechanism of legumain activation. After trans-activation, rLEG-1 worked best at pH 5·5 and 35–39 °C and cleaved a legumain-specific artificial substrate as well as the natural substrates bovine collagen types I and II. In a clinical vaccination trial, rLEG-1 did not protect against challenge infection. Results of in vitro characterization, transcription pattern and localization enhance the presumption that LEG-1 participates in digestion processes of D. viviparus. Since rLEG-1 needs trans-activation through a cathepsin, it is probably involved in an enzyme cascade and therefore remains interesting as a candidate in a multi-component vaccine.
Objectives: The aim of this report was to assess the clinical effectiveness of two Gene expression profiling (GEP) and two expanded immunohistochemistry (IHC) tests compared with current prognostic tools in guiding the use of adjuvant chemotherapy in patients with early breast cancer.
Methods: A systematic review of the evidence on clinical effectiveness of OncotypeDX, IHC4, MammaPrint, and Mammostrat, compared with current clinical practice using clinicopathological parameters, in women with early breast cancer was conducted. Ten databases were searched to include citations to May 2016.
Results: Searches identified 7,064 citations, of which forty-one citations satisfied the criteria for the review. A narrative synthesis was performed. Evidence for OncotypeDX demonstrated the impact of the test on decision making and there was some support for OncotypeDX predicting chemotherapy benefit. There were relatively lower levels of evidence for the other three tests included in the analysis. MammaPrint, Mammostrat, and IHC4 tests were limited to a small number of studies. Limitations in relation to study design were identified for all tests.
Conclusions: The evidence base for OncotypeDX is considered to be the most robust. Methodological weaknesses relating to heterogeneity of patient cohorts and issues arising from the retrospective nature of the evidence were identified. Further evidence is required for all of the tests using prospective randomized controlled trial data.
This study aimed to test the expression of maspin in invasive fungal rhinosinusitis and explore its value in diagnosing invasive fungal rhinosinusitis.
Forty-two fungal rhinosinusitis cases (12 invasive and 30 non-invasive) were selected as the experimental group, and 30 chronic rhinosinusitis cases comprised the control group. Maspin expression was assessed in nasal mucous membrane specimens by immunohistochemical staining.
Compared with the control group, maspin expression was down-regulated in the fungal rhinosinusitis group (p < 0.05). Furthermore, the staining score for maspin was lowest in the invasive fungal rhinosinusitis group, as compared with both the non-invasive fungal rhinosinusitis group and the control group (p < 0.05). A maspin staining score of 5.70 was the critical value for diagnosis of invasive fungal rhinosinusitis, with sensitivity and specificity of 91.7 per cent and 88.3 per cent, respectively.
The results of this study suggest that the maspin staining score may be a biomarker for effective and rapid diagnosis of invasive fungal rhinosinusitis.
The clinical and prognostic significance of CD44 variant isoform expression in nasopharyngeal carcinoma is not well known. This study aimed to clarify whether CD44 variant isoform expression serves as a prognostic factor in nasopharyngeal carcinoma.
Forty-two nasopharyngeal carcinoma patients, who underwent concurrent chemoradiotherapy as the initial treatment, were the subjects of investigation. Expression of CD44 variant isoforms, CD44v3, CD44v4, CD44v5, CD44v6 and CD44v7, in nasopharyngeal carcinoma was assessed in relation to concurrent chemoradiotherapy resistance and disease-specific survival of the patients.
Results and conclusion:
The patients with CD44v6 high expression showed a clinically incomplete response to concurrent chemoradiotherapy at the primary site. The disease-specific survival rate was lower in patients with high expression of CD44v3 than in those with low expression. These results suggest that analysis of CD44v6 and CD44v3 expression is useful in estimating prognosis and determining effective treatment strategies in nasopharyngeal carcinoma.
Dynamics of myofiber differentiation/maturation in porcine skeletal muscle is associated with domestication, breeding and rearing conditions. This study was aimed to comparatively elucidate the age-dependent myosin heavy chain (MyHC) isoform expression and transition pattern in domestic and wild pig (WP) skeletal muscle from birth until adulthood. Domestic pigs (DPs) of Large White breed raised in conventional production system were compared with WPs reared in a large hunting enclosure. Muscle samples for immuno/enzyme histochemistry were taken from the longissimus dorsi muscle within 24 h postmortem at 24 to 48 h, 21 to 23 days, 7 months and ~2 years postpartum. Based on the antibody reactivity to MyHCs (NCL-MHCs, A4.74, BF-F3) and succinate dehydrogenase activity, myofibers were classified into I, I/IIa, IIa, IIx and IIb types. In addition, foetal MyHC expression was determined with the use of F158.4C10 antibody. Maturation of the longissimus dorsi muscle in the WP was characterized by an accelerated transformation of the fast to slow MyHC during the first hours postpartum, followed by differentiation towards oxidative myofibers in which type I, IIa and IIx MyHCs predominated. In the DP, the transformation shifted towards glycolytic myofibers that expressed MyHC-IIb. The expression of foetal MyHC was higher in the DP than in the WP at 1 day of age, and the decline in the foetal MyHC during the first 3 weeks was more rapid in the WP than in the DP denoting an accelerated early postnatal muscle maturation in WP than DP piglets. All foetal MyHC-positive myofibers co-expressed IIa isoform, but not vice versa. The intense myofiber hypertrophy was evident from 3 weeks until 7 months of age. In this period, the myofiber cross-sectional area increased up to 10- and 20-fold in the WP and the DP, respectively. In the DP, the hypertrophy of all myofiber types was more pronounced than in the WP, particularly the hypertrophy of IIx and IIb myofibers. To summarize, the comparison between growing DP with wild ancestors showed that genetic selection and rearing conditions lead to substantial changes in the direction and intensity of postnatal MyHC transformation as evidenced by different proportion of individual myofiber types and differences in their hypertrophic potential.
Leptospirosis is a zoonosis caused by bacteria of the genus Leptospira. The disease is globally distributed and a major public health concern. The Norway rat (Rattus norvegicus) is the main reservoir of the pathogen in urban slums of developing and developed countries. The potential routes of intra-specific leptospire transmission in rats are largely unknown. Herein, we identified pathogenic Leptospira spp. in breast tissue and milk of naturally infected rats. We examined kidney, breast tissue and milk from 24 lactating rats for the presence of leptospires using immunofluorescence, immunohistochemistry, polymerase chain reaction (PCR) and scanning electronic microscopy. All 24 rats had evidence for Leptospira in the kidneys, indicating chronic carriage. The majority of kidney-positive rats had detectable leptospires in milk (18, 75%) and breast tissue (16, 67%), as evidenced by immunofluorescence assay and immunohistochemistry. Four (17%) milk samples and two (8%) breast tissue samples were positive by quantitative real-time PCR. Scanning electron microscopy confirmed the presence of leptospires in breast tissue. No major pathological changes in breast tissue were found. This study, for the first time, identified leptospires in the milk and breast tissue of wild Norway rats, suggesting the possibility of milk-borne transmission of leptospirosis to neonates.
The cholinergic system is involved in cortical plasticity, attention, and learning. Within the visual cortex the cholinergic system seems to play a role in visual perception. The cholinergic neurons which project into the visual cortex are located in the basal forebrain. It has been shown that mice deficient for the low-affinity neurotrophin receptor p75NTR display increased numbers of cholinergic neurons in the basal forebrain and a denser cholinergic innervation of the hippocampus. This prompted us to analyze whether the cholinergic system is altered in adult p75NTR deficient mice. By analyzing the densities of cholinergic fibers within layer IV as well as within layer V of the visual cortex, we found that adult p75NTR deficient mice display increased cholinergic fiber densities. However, this increase was not accompanied by an increase in the density of local cholinergic neurons within the visual cortex. This indicates that the enhanced cholinergic innervation of the visual cortex is due to alteration of the cholinergic neurons located in the basal forebrain, projecting to the visual cortex. The increased cholinergic innervation of the visual cortex makes the p75NTR deficient mice an attractive model to study the necessity of the cholinergic system for the visual cortex.
Sinonasal teratocarcinosarcoma (TCS) are highly aggressive and rare malignant tumours arising from the heterogeneous admixture of components of all the three germ cell layers. There are <60 cases that have been reported in the literature. In spite of aggressive therapy, the average survival is <3 years with multimodality therapy. In total, 70% of the patients who survived >1 year received regimen of combined surgery and adjuvant therapies and this suggests that aggressive therapeutic approaches may improve the treatment outcome.
Materials and methods
We are reporting a case study of sinonasal TCS treated with initial surgery followed with concurrent chemoradiotherapy using intensity-modulated radiotherapy (IMRT) technique. The concurrent chemotherapy and adjuvant chemotherapy consisted of carboplatin and etoposide.
This aggressive treatment protocol of concurrent chemoradiation along with adjuvant chemotherapy is well tolerated and produced 5-year locoregional control and survival without any long-term morbidities.
Our treatment protocol was well tolerated and the outcome in this individual patient has been encouraging. This could justify a combined modality approach with post-operative simultaneous-integrated boost-IMRT and chemotherapy (concurrent and adjuvant) for future patient with sinonasal TCS.
This study aimed to evaluate the association of a disintegrin and metalloproteinase-33 protein (‘ADAM-33’) expression in vocal polyp formation and to determine its correlation with clinical characteristics.
Medical charts and histological sections of 32 patients diagnosed with vocal polyps who underwent surgery were analysed. Controls were histopathologically normal vocal fold tissues obtained from 36 patients who underwent surgery for laryngeal squamous cell carcinoma. Immunohistochemical staining was performed to detect ADAM-33 expression in epithelial cells, stroma and vessels.
All epithelial, stromal and vascular staining scores were significantly greater in polyp tissue than in controls (p < 0.001). Stromal ADAM-33 staining scores were higher in vocal polyp patients with a symptom duration of less than six months (p < 0.05). Vocal overuse or the presence of reflux symptoms, sinonasal symptoms or allergy did not affect ADAM-33 immunostaining scores (p = 0.05).
In this study, ADAM-33 immunostaining was significantly increased in vocal polyps. Therefore, over-expression of this protein may be associated with vocal polyp pathogenesis.
The aim of the present research was to trace CD34+ stromal fibroblastic cells (CD34+ SFCs) in the palatal connective tissue harvested for muco-gingival surgical procedures and in granulation tissues from periodontal pockets using immunohistochemical and transmission electron microscopy. Immunohistochemical analysis targeted the presence of three antigens: CD31, α-smooth muscle actin (α-SMA), and CD34. In the palate, CD31 staining revealed a colored inner ring of the vessels representing the endothelium, α-SMA+ was located in the medial layer of the vasculature, and CD34 was intensely expressed by endothelial cells and artery adventitial cells (considered to be CD34+ SFCs). Granulation tissue showed the same pattern for CD31+ and α-SMA, but a different staining pattern for CD34. Ultrastructural examination of the palatal tissue highlighted perivascular cells with fibroblast-like characteristics and pericytes in close spatial relationship to endothelial cells. The ultrastructural evaluation of granulation tissue sections confirmed the presence of neovasculature and the inflammatory nature of this tissue. The present study traced the presence of CD34+ SFCs and of pericytes in the palatal connective tissue thus highlighting once more its intrinsic regenerative capabilities. The clinical and systemic factors triggering mobilization and influencing the fate of local CD34+SCFs and other progenitors are issues to be further investigated.
The aim of the work was to analyse changes in the location and morphological characteristics of calbindin (CB)-immunoreactive (IR) neurons of the thoracic spinal cord of C57BL/6N male mice after completion of a 30-day space flight on board the BION-M1 biosatellite (Russia, 2013). Space flight induced multidirectional changes of the number and morphological parameters of CB-positive neurons. The number of IR neurons increased in laminae I (from 10 to 17 neurons per section), II (from 42 to 67 cells per section) and IX (from two neurons per segment to two neurons per section), but CB disappeared in neurons of lamina VIII. Weightlessness did not affect the number of CB-IR neurons in laminae III–V and VII, including preganglionic sympathetic neurons. The cross-sectional area of CB-IR neurons decreased in lamina II and VII (group of partition cells) and increased in laminae III–V and IX. After a space flight, few very large neurons with long dendrites appeared in lamina IV. The results obtained give evidence about substantial changes in the calcium buffer system and imbalance of different groups of CB-IR neurons due to reduction of afferent information under microgravity.
The aim of this study was to determine whether allergic rhinitis can induce structural changes in the synapse formation in the hippocampus of BALB/c mice immunocytochemically.
Allergic rhinitis was induced in mice by two intra-peritoneal injections of ovalbumin administered with a one-week interval. After two weeks, the sensitised mice were challenged with an intra-nasal injection of ovalbumin for two weeks. To analyse the hippocampal synaptic structures, sections were immunostained with antibodies against glutamic acid decarboxylase 65 and glutamic acid decarboxylase 67 (for γ-aminobutyric acid-ergic terminals), synaptophysin (for glutamatergic and γ-aminobutyric acid-ergic terminals) and spinophilin (for dendritic spines). The number of nasal rubbing movements was significantly greater in the allergic rhinitis mice than in the control mice. However, the expression patterns of the four above-mentioned synaptic markers in the hippocampus showed no detectable difference between the allergic rhinitis and control mice.
Results and Conclusion:
These data indicate that the synaptic structure in the hippocampus might remain unaltered in allergic rhinitis patients.