Multimodality imaging of extra-nodal lymphoma in the head and neck.

Malignant lymphomas represent approximately 5% of all malignant neoplasms of the head and neck. The head and neck region is the second most frequent anatomical site of extra-nodal lymphomas (after the gastrointestinal tract). Most are non-Hodgkin's lymphomas of B-cell lineage, and overall diffuse large B-cell lymphoma is the most common type. They can present in highly variable appearances in different anatomical subsites in the head and neck. There is little literature on their imaging appearances on different imaging methods including ultrasound, magnetic resonance imaging (MRI), computed tomography (CT), and integrated positron-emission tomography (PET)/CT. The review aims to illustrate the presentation of histopathological-proven extra-nodal lymphoma in the head and neck using various imaging methods.

Composition of the mucosa-associated microbiota along the entire gastrointestinal tract of human individuals.

Background: Homeostasis of the gastrointestinal tract depends on a healthy bacterial microbiota, with alterations in microbiota composition suggested to contribute to diseases. To unravel bacterial contribution to disease pathology, a thorough understanding of the microbiota of the complete gastrointestinal tract is essential. To date, most microbial analyses have either focused on faecal samples, or on the microbial constitution of one gastrointestinal location instead of different locations within one individual. Objective: We aimed to analyse the mucosal microbiome along the entire gastrointestinal tract within the same individuals. Methods: Mucosal biopsies were taken from nine different sites in 14 individuals undergoing antegrade and subsequent retrograde double-balloon enteroscopy. The bacterial composition was characterised using 16 S rRNA sequencing with Illumina Miseq. Results: At double-balloon enteroscopy, one individual had a caecal adenocarcinoma and one individual had Peutz-Jeghers polyps. The composition of the microbiota distinctively changed along the gastrointestinal tract with larger bacterial load, diversity and abundance of Firmicutes and Bacteroidetes in the lower gastrointestinal tract than the upper gastrointestinal tract, which was predominated by Proteobacteria and Firmicutes. Conclusions: We show that gastrointestinal location is a larger determinant of mucosal microbial diversity than inter-person differences. These data provide a baseline for further studies investigating gastrointestinal microbiota-related disease.

The gastrointestinal microbiota and its role in oncogenesis.

Advances in research techniques have made it possible to map the microbial communities in the gastrointestinal (GI) tract, where the majority of bacteria in the human body reside. Disturbances in these communities are referred to as dysbiosis and have been associated with GI cancers. Although dysbiosis is observed in several GI malignancies, the specific role of these changes has not been understood to the extent of Helicobacter pylori (HP) in gastric cancer (GC). This review will address the bacterial communities along the GI tract, from the oral cavity to the anal canal, particularly focusing on bacterial dysbiosis and carcinogenesis. Just as non-HP bacteria in the stomach may interact with HP in gastric carcinogenesis, the same may hold true for other GI tract malignancies, where an interplay between microbes in carcinogenesis seems conceivable, especially in colorectal cancer (CRC). In the last part of this review we will discuss the potential mechanisms of bacterial dysbiosis in GI carcinogenesis.

Upregulation of pituitary adenylate cyclase activating polypeptide and its receptor expression in the rat carotid body in chronic and intermittent hypoxia.

The carotid body (CB) plays important roles in cardiorespiratory changes in chronic and intermittent hypoxia. Pituitary adenylate cyclase activating polypeptide (PACAP) is involved in the regulation of respiratory chemoresponse. We hypothesized an upregulation of the expressions of PACAP and its receptor (PAC1) in the rat CB in chronic and intermittent hypoxia. The CB expressions of PACAP and PAC1 were examined in rats breathing 10% O(2) (in isobaric chamber for chronic hypoxia, 24 h/day) or in intermittent hypoxia (cyclic between air and 5% O(2) per minute, 8 h/day) for 7 days. Immunohistochemical studies showed that the PACAP and PAC1 proteins were localized in CB glomic clusters containing tyrosine hydroxylase. The proportional amount of cells with positive staining of PACAP and PAC1 was significantly increased in both hypoxic groups when compared with the normoxic control. In addition, the mRNA level of PAC1 expression was markedly elevated in the hypoxic groups, despite no changes in the PACAP expression. These results suggest an upregulation of PACAP and its receptor expression in the rat CB under chronic and intermittent hypoxic conditions. The PACAP binding to its receptor could activate the PKA signaling pathway leading to an increased CB excitability under hypoxic conditions.

Early detection of central airway lung cancer in smokers with silicosis.

BACKGROUND: Smokers with silicosis are at increased risk of lung cancer. OBJECTIVE: To evaluate the feasibility of using autofluorescence bronchoscopy after sputum examination for early detection of large airway lung cancer and factors associated with the presence of cancerous and pre-cancerous lesions among smokers with silicosis. METHODS: Subjects at the pneumoconiosis clinic were recruited if they fulfilled the following criteria: 1) age ≥40 years, 2) smoking history of ≥20 pack-years and 3) confirmed diagnosis of silicosis. Sputum specimens were collected for cytology/cytometry examination and autofluorescence bronchoscopy was performed in subjects with an abnormal sputum result. RESULTS: A total of 48 subjects were recruited during the study period. The mean age and smoking history were respectively 63 ± 10 years and 51 ± 30 pack-years. Intraepithelial lung cancers and pre-neoplastic lesions (squamous metaplasia or above) were detected in respectively 2 (4.2%) and 14 (29.2%) subjects. The proportions of current smokers (75.0% vs. 40.6%, P = 0.03) and asbestos exposure (37.5% vs. 9.4%, P = 0.04) were significantly higher in subjects with the above lesions compared with those without. CONCLUSIONS: Sputum examination followed by autofluorescence bronchoscopy may be a useful way of identifying cancerous/pre-cancerous lesions among silicotic smokers. Current smoking and asbestos exposure were associated with these lesions.

Epidermal inclusion cyst of the breast: a rare benign entity.

Epidermal inclusion cyst (EIC) arising from the breast is an uncommon benign condition. We report two cases of enlarging EIC of the breast in two women in their forties. The diagnosis of this condition may not be straightforward with imaging alone if an EIC presents as an enlarging lump in the breast and mimics a benign breast lesion, most commonly a fibroadenoma or malignant lesion with benign imaging features. Excision is usually recommended for a definite histopathological diagnosis and for the prevention of potential risks of malignant transformation. Asymptomatic stable lesions do not require treatment; biopsy is unnecessary, and follow-up imaging suffices if typical sonographic and clinical findings are found.

Merosin-deficient congenital muscular dystrophy in two siblings.

Congenital muscular dystrophies are a group of heterogeneous inherited autosomal recessive disorders. The so-called 'pure' or 'occidental' form is further divided into merosin-positive and merosin-negative subgroups. Merosin is also expressed in the nervous system and its deficiency could affect development of the nervous system. The authors report two siblings with merosin-negative congenital muscular dystrophy. The clinical picture, biopsy findings, and abnormalities as detected by the magnetic resonance imaging of the two patients are presented.

HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains.

HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca2+ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca2+ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721deltaC and T7721deltaN cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721deltaC cells, but not affected in T7721deltaN cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca2+ mobilization although each domain may play different roles.

Expression, immunolocalization, and functional activity of Na+/H+ exchanger isoforms in mouse endometrial epithelium.

The luminal fluid microenvironment of the uterus is important for sperm capacitation and embryo development. In an attempt to understand the possible role of Na(+)/H(+) exchangers (NHEs) in uterine function, the mRNAs of different NHE isoforms as well as their subcellular localization (apical versus basolateral) and functional activity were investigated in mouse endometrial epithelial cells using reverse transcriptase-polymerase chain reaction (RT-PCR), immunohistochemistry, and intracellular pH (pH(i)) measurement techniques. The presence of NHE1, NHE2, and NHE4, but not NHE3 mRNAs were revealed by RT-PCR. Immunostaining showed that NHE1, NHE2, and NHE4 were present in both apical and basolateral membranes. The pH(i) recovery from intracellular acidification was Na(+)-dependent; however, the rate of pH(i) recovery depending on basolateral Na(+) was 12.4 times faster than that depending on apical Na(+). The Na(+)-dependent rate of pH(i) recovery was also inhibited by amiloride, indicating H(+) extrusion through NHEs; however, the amiloride sensitivity of the apical membrane was less than that of the basolateral membrane, suggesting the involvement of different types of NHEs in the two membranes. The results indicate that the basolaterally located NHE1, NHE2, and NHE4, in addition to participating in the homeostatic control of intracellular pH, may play a role in H(+) extrusion in order to achieve transepithelial HCO(3)(-) secretion. The apically located NHEs may be involved in mediating Na(+) absorption as alternatives of or complementary to epithelial Na(+) channels.

Life threatening acute epiglottitis in acute leukemia.

We report an 8-year-old boy who developed a life-threatening acute epiglottitis during induction chemotherapy for acute promyelocytic leukemia. He survived the infection with emergency tracheostomy, treatment with broad spectrum antibiotics and amphotericin, and the use of granulocyte-macrophage colony stimulating factor. No organism was identified. A literature review identified 18 cases of acute epiglottitis in cancer patients. Sixteen of them were suffering from hematologic malignancies and three patients had received bone marrow transplantation. Unlike the usual case of epiglottitis, the majority (15 out of 18) of affected patients were adults and none of the infections was associated with Haemophilus influenzae. Streptococcus pneumoniae and Candida albicans were the most frequently identified pathogens. Early recognition and aggressive supportive care are required for successful management.

Local regulation of anion secretion by pituitary adenylate cyclase-activating polypeptide in human colonic T84 cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel hypothalamic peptide, which has been shown to exert various functions in a number of tissues, including exocrine and endocrine tissues. The present study investigated the role of local PACAP in the control of anion secretion by the human colonic T84 cell. Both bioactive forms of PACAP-27 and PACAP-38 gave rise to a dose-dependent increase in the short-circuit current (I(SC)). However, there was a reversal in the order of potency observed at different concentration ranges for the two bioactive forms. PACAP-27 was greater than PACAP-38 when the peptide concentrations were below 10 n m; PACAP-38 was greater than PACAP-27 in the range of 10-80 n m. The effects of both PACAP forms were restricted to the apical aspect of the T84 cell. The I(SC)responses to both PACAP-27 and PACAP-38 were suppressed respectively by the non-selective Cl(-)channel blocker, diphenylamine-dicarboxylic acid (DPC), by the Ca(2+)dependent Cl(-)channel blocker, diisothiocyanatostilbene-disulfonic acid (DIDS) and by the Ca(2+)chelator, BAPTA-AM, indicating the involvement of Ca(2+). The expression of PACAP was demonstrated and localized specifically to the perinuclear cytoplasm of the T84 cell using immunocytochemistry, indicating its epithelial origin. Thus, the present data suggest that, in addition to the well-known cAMP-dependent pathway, PACAP may play a role in regulating colonic Cl(-)secretion via a Ca(2+)-dependent pathway, perhaps through two distinct PACAP receptor subtypes. Moreover, the regulation of anion secretion by T84 cells may be mediated by locally formed PACAP in an autocrine or paracrine fashion.

Testicular hormonal regulation of the renin-angiotensin system in the rat epididymis.

Evidence for the existence of an intrinsic angiotensin system based on locally formed angiotensinogen as a precursor for angiotensin production has been demonstrated in the rat epididymis. The data strongly support the presence of an epididymal renin-angiotensin system (RAS) which may be important for epididymal and sperm functions. In the present study, the effects of castration and testicular hormonal replacement on the expression of RAS components from the rat epididymis are investigated at the gene and protein levels. Results from northern blot and western blot analyses consistently showed that the expression of angiotensinogen mRNA and protein was apparently abolished by castration whereas their expression was completely restored to control levels when the castrated rats were hormonally replaced with either testosterone alone or with combined testosterone and estradiol. Northern blot did not detect any signal for angiotensinogen mRNA while western blot could detect a weak signal for angiotensinogen protein when the castrated rats were replaced with estradiol alone. Renin could be detected neither in control, castrated nor hormonally replaced rats. Moreover, the expression of angiotensin II receptor, type I (AT1) was almost abolished by castration as demonstrated by northern blot and reverse transcription-polymerase chain reaction. These data indicate that the expression of RAS by the rat epididymis at the levels of its precursor angiotensinogen and its receptor AT1, is subject to the regulation of testicular hormones and its expression appears to be predominantly testosterone-dependent.

Concurrent and independent HCO3- and Cl- secretion in a human pancreatic duct cell line (CAPAN-1).

The present study investigated both HCO-3 and Cl- secretions in a human pancreatic duct cell line, CAPAN-1, using the short-circuit current (Isc) technique. In Cl-/HCO-3-containing solution, secretin (1 microM) or forskolin (10 microM) stimulated a biphasic rise in the Isc which initially reached a peak level at about 3 min and then decayed to a plateau level after 7 min. Removal of external Cl- abolished the initial transient phase in the forskolin-induced Isc while the plateau remained. In HCO-3/CO2-free solution, on the contrary, only the initial transient increase in Isc was prominent. Summation of the current magnitudes observed in Cl--free and HCO-3-free solutions over a time course of 10 min gave rise to a curve which was similar, both in magnitude and kinetics, to the current observed in Cl-/HCO-3-containing solution. Removal of external Na+ greatly reduced the initial transient rise in the forskolin-induced Isc response, and the plateau level observed under this condition was similar to that obtained in Cl--free solution, suggesting that Cl--dependent Isc was also Na+-dependent. Bumetanide (50 microM), an inhibitor of the Na+-K+-2Cl- cotransporter, and Ba2+ (1 mm), a K+ channel blocker, could reduce the forskolin-induced Isc obtained in Cl-/HCO-3-containing or HCO-3-free solution. However, they were found to be ineffective when external Cl- was removed, indicating the involvement of these mechanisms in Cl- secretion. On the contrary, the HCO-3-dependent (in the absence of external Cl-) forskolin-induced Isc could be significantly reduced by carbonic anhydrase inhibitor, acetazolamide (45 microM). Basolateral application of amiloride (100 microM) inhibited the Isc; however, a specific Na+-H+ exchanger blocker, 5-N-methyl-N-isobutylamiloride (MIA, 5-10 microM) was found to be ineffective, excluding the involvement of the Na+-H+ exchanger. However, an inhibitor of H+-ATPase, N-ethylmaleimide did suppress the Isc (IC50 = 22 microM). Immunohistochemical studies also confirmed the presence of a vacuolar type of H+-ATPase in these cells. H2DIDS (100 microM), an inhibitor of Na+-HCO-3 cotransporter, was without effect. Apical addition of Cl- channel blocker, diphenylamine-2,2'-dicarboxylic acid (DPC, 1 mm), but not disulfonic acids, DIDS (100 microM) or SITS (100 microM), exerted an inhibitory effect on both Cl- and HCO-3-dependent forskolin-induced Isc responses. Histochemical studies showed discrete stainings of carbonic anhydrase in the monolayer of CAPAN-1 cells, suggesting that HCO-3 secretion may be specialized to a certain population of cells. The present results suggest that both HCO-3 and Cl- secretion by the human pancreatic duct cells may occur concurrently and independently.

Nodular histiocytic/mesothelial hyperplasia: a lesion potentially mistaken for a neoplasm in transbronchial biopsy.

This report describes two examples of nodular histiocytic/ mesothelial hyperplasia as seen in transbronchial biopsy that initially led to serious consideration of neuroendocrine neoplasm or meningioma. The biopsies showed nodular collections of cohesive polygonal or round cells with ovoid or deeply grooved nuclei and a moderate amount of finely granular cytoplasm. Nuclear pleomorphism was mild. Immunohistochemical studies showed few cells staining for cytokeratin and the mesothelial marker HBME-1, whereas most cells were decorated by the histiocytic marker PG-M1 (CD68). This lesion appears to be identical to nodular mesothelial hyperplasia as described in hernia sacs and mesothelial/monocytic incidental cardiac excrescences, and we propose modifying the designation to "nodular histiocytic/mesothelial hyperplasia" to take into account the marked predominance of histiocytes over mesothelial cells. The clues to recognition of the true nature of the lesion are clinicopathologic correlation and identification of strips of low cuboidal (mesothelial) cells in the vicinity, and the diagnosis can be further confirmed by immunohistochemical staining. Nodular histiocytic/mesothelial hyperplasia probably results from irritation to the mesothelial lining by various causes leading to focal aggregation of histiocytes within retraction pockets or crevices of the serosal cavity.

Evaluation of a histogenetic classification for thymic epithelial tumours.

We reviewed 87 thymic epithelial tumours from Chinese patients and typed them according to the Marino and Müller-Hermelink classification as updated by Kirschner and Müller-Hermelink in 1989. Related categories were grouped for statistical analyses: group 1, medullary thymoma and mixed thymoma; group 2, cortical predominant thymoma; group 3, cortical thymoma and well-differentiated thymic carcinoma; group 4, other thymic carcinomas; and group 5, unclassified. Group 3 tumours were more frequently associated with the myasthenia gravis syndrome compared with group 1 tumours (P = 0.001). They also presented at a more advanced stage. Groups 1 and 2 showed an excellent prognosis (100% survival at 10 years). The 10-year survival for groups 3 and 4 patients was 40% and 30% respectively. Pure medullary thymoma made up a higher proportion of our cases (10.3%) than those of a similar Caucasian study (5.3%). The eight thymic carcinomas (group 4) included two thymic lymphoepitheliomas. We conclude that the histogenetic classification evaluated shows a clear correlation with prognosis and clinical features, even when tested on separate geographic groups, where pathogenetic factors may be different. A common approach to classification of thymic epithelial tumours would greatly facilitate future studies on these possible differences.

Factors affecting fetal loss in induction of ovulation with gonadotropins: increased abortion rates related to hormonal profiles in conceptual cycles.

Thirty-six first-trimester abortions (9.7%), 16 second-trimester abortions (4.3%), 11 ectopic pregnancies (2.9%), and 10 stillbirths (2.7%) occurred in 373 conceptual cycles after gonadotropin induction of ovulation. Fetal wastage was higher in spontaneous pregnancies that occurred before therapy (54.3%, p less than 0.0001) and lower with subsequent spontaneous pregnancies (10.1%, p less than 0.05). Significant risk factors for overall fetal loss during induced ovulation were a continuous rise of estrogen excretion until ovulation (p less than 0.01) and previous abortion (p less than 0.05). For first-trimester abortion, the risk factor was continuous estrogen rise (p less than 0.01); for second-trimester abortion, the risk factors were a low luteal pregnanediol-to-estrogen excretion ratio (p less than 0.002), increased age at conception (p less than 0.02), and high baseline estrogen excretion (p less than 0.05). Multiple pregnancy was not significant. The continuous rising estrogen pattern may serve as a marker of abnormal oocyte maturation. We propose that future studies on infertility treatment should report on pregnancy outcome.

Smoking, passive smoking and histological types in lung cancer in Hong Kong Chinese women.

In a case control study in Hong Kong, 445 cases of Chinese female lung cancer patients all confirmed pathologically were compared with 445 Chinese female healthy neighbourhood controls matched for age. The predominant histological type was adenocarcinoma (47.2%). The relative risk (RR) in ever-smokers was 3.81 (P less than 0.001, 95% CI = 2.86, 5.08). The RRs were statistically significantly raised for all major cell types with significant trends between RR and amount of tobacco smoked daily. Among never smoking women, RR for passive smoking due to a smoking husband was 1.65 (P less than 0.01, 95% CI = 1.16, 2.35) with a significant trend between RR and amount smoked daily by the husband. When broken down by cell types, the numbers were substantial only for adenocarcinoma (RR = 2.12, P less than 0.01, 95% CI = 1.32, 3.39) with a significant trend between RR and amount smoked daily by the husband. The results suggest that passive smoking is a risk factor for lung cancer, particularly adenocarcinoma in Hong Kong Chinese women who never smoked.