Regions Of Mucosa Research Articles

Multistep laryngeal carcinogenesis helps our understanding of the field cancerisation phenomenon: a review

In this paper, we try to briefly review the most recent knowledge on head and neck cancer, and especially multistep laryngeal carcinogenesis, and to simply explain how this has modified our understanding of field cancerisation phenomenon. Experimental studies, made possible by the recent evolution of microdissection systems, have demonstrated that the `spatial progression' of the histopathological phenotype in the surroundings of malignant or premalignant head and neck lesions correlates with molecular progression. Such a `spatial progression' can be hypothesised to reflect temporal progression. The field cancerisation process has been divided into three phases, each with its own histological and molecular characteristics. Each of these phases may have clinical implications: detection and monitoring of fields may help cancer prevention (molecular epidemiology), early detection of recurrence (or, more exactly, of second field tumours (SFTs)) (molecular diagnostics) and prognostic prediction after treatment. This model appears plausible, especially in explaining the development of multiple primary tumours (MPTs) in adjacent head and neck mucosal regions, with peculiar clinical and prognostic implications: These tumours can be defined as multiple field tumours (SFTs). However, the model, in our opinion, does not convincingly explain the development of second primary tumours (SPTs) at more distant sites, such as the lung, colon and prostate.

Effects of Exposure to Genistein and Estradiol on Reproductive Development in Immature Male Mice Weaned from Dams Adapted to A Soy-based Commercial Diet

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may adversely affect the development of male reproductive system. Twenty one-day-old ICR mice weaned from dams fed with a soybean-based diet throughout gestation and lactation were exposed by gavage to genistein (2.5 mg/kg b.w./day) or 17beta-estradiol (7.5 microg/kg b.w./day) for five weeks. Corn oil was used as a negative control. The animals were fed with a casein-based AIN-76A diet throughout the experimental periods. There were no significant differences in body and organ weights of mice among experimental groups. No significant differences in sperm counts and sperm motile characteristics were found between control and genistein groups. Treatment of 17beta-estradiol caused a significant decrease in prostate weight and epididymal sperm counts compared to the control (p<0.05). The levels of phospholipid hydroxide glutathione peroxidase in the testis and prostate of mice exposed to genistein or 17beta-estradiol were significantly higher than that of the control mice (p<0.05). 17beta-estradiol treatment caused degeneration and apoptosis of germ cells in the testis, depletion and degeneration in the epididymal epithelium, and hyperplasia of mucosal fold region in the prostate of mice. Genistein treatment did not cause any lesion in the testis, epididymis, and prostate. These results suggest that dietary uptake of genistein during juvenile period may not affect male reproductive development and functions.

Exposure to genistein does not adversely affect the reproductive system in adult male mice adapted to a soy-based commercial diet

Genistein, a soybean-originated isoflavone, is widely consumed by humans for putative beneficial health effects but its estrogenic activity may affect adversely the development of male reproductive system. Five-week-old ICR mice were purchased and fed with a soybean-based Purina Chow diet until 6 months of age. The animals were exposed by gavage to genistein (2.5 mg/kg/day) or 17beta-estradiol (7.5 microg/kg/day) for five weeks. Corn oil was used for the negative control. The animals were fed the casein-based AIN-76A diet throughout the experimental periods. There were no significant differences in body and organ weights of mice among experimental groups. No significant differences in sperm counts and sperm motile characteristics were found between the control and the genistein groups. Treatment of 17beta-estradiol caused a significant decrease in epididymal sperm counts compared to the control (p<0.05). The level of phospholipid hydroxide glutathione peroxidase in the epididymis of mice exposed to genistein was significantly higher than that of the control mice (p<0.05). 17beta-estradiol treatment caused a reduction of germ cells in the testis and hyperplasia of mucosal fold region in the prostate of mice. Genistein treatment did not cause any lesion in the testis, epididymis, and prostate. These results suggest that dietary uptake of genistein at adult stage of life may not affect male reproductive system and functions.

Vaccine candidates in STD.

Sexually transmitted diseases (STDs) are caused by organisms that infect the mucosal surfaces of the genitourinary tract. In spite of its public health importance, current STD vaccine research lags behind work against pathogens that target another mucosal region, the respiratory tract. In the latter case, live-attenuated viral vaccines, killed whole-cell bacterial vaccines, subunit/protein bacterial vaccines, and bacterial polysaccharide vaccines have been enormously successful. To move STD vaccine research forward, complex issues must be resolved. Those include selection of an appropriate antigen (e.g. scientific feasibility and intellectual property rights), the manufacture of the vaccine (e.g. delivery systems, formulation processes, and production steps), and the appropriate public health approach (e.g. medical indications and marketing aspects). Particular scientific problems have delayed STD vaccine development, like incomplete attenuation (human herpes simplex virus type 2), accentuated immunopathology (Chlamydia trachomatis), poor immunogenicity (Treponema pallidum), and broad antigenic heterogeneity (Neisseria gonorrhoeae). Nevertheless, efforts continue with the use of protein antigens: for example, the haemolysin toxoid of Haemophilus ducreyi; the major outer membrane protein(s) of N. gonorrhoeae and C. trachomatis; the glycoprotein D of human herpes simplex virus type 2; and the proteins E6 and E7 of human papilloma virus. It may be predicted that eventual STD vaccines (administered either for prophylaxis or for therapy) will use approaches that include (1) live-attenuated viruses, (2) subunit proteins or inactivated whole organisms given with mucosal adjuvants or with cellular immune response adjuvants, and (3) DNA plasmids expressing the vaccine antigen.

Immunolocalization of inducible nitric oxide synthase and 3-nitrotyrosine in recurrently inflamed, human palatine tonsils.

The purpose of this study was to evaluate the possible involvement of nitric oxide and its toxic metabolite--peroxynitrite--in the pathogenesis of recurrent tonsillitis. Tonsil specimens with recurrent inflammation were obtained from patients who required tonsillectomies as surgical treatment for their conditions. The relatively normal tonsils were obtained from patients who underwent uvulo-palato-pharyngoplasty for habitual snoring or obstructive sleep apnea. The sites of inducible nitric oxide synthase (iNOS) expression in the tonsil specimens were examined with an immunohistochemical technique. The possible production of peroxynitrite was evaluated by immunolabeling of 3-nitrotyrosine (3-NT) as its biological footprint. Each section was given a score of 0 to 4 according to the labeling intensity seen, with the highest number representing the highest labeling intensity. We found that tonsils with recurrent inflammation had iNOS expression mainly in the mucosal epithelium, subepithelial regions and vascular endothelium. The parenchyma of the tonsils, where T- and B-cell clones are located, showed little iNOS immunoreactivity. The accumulation of 3-NT had a similar distribution pattern to that of iNOS expression. However, the normal tonsils showed limited iNOS expression on mucosal epithelium and rare 3-NT accumulation. Recurrently inflamed tonsils had significantly higher labeling scores for both iNOS and 3-NT compared to normal tonsils. Further, a higher iNOS score correlated with a higher 3-NT accumulation. These data suggest that iNOS expression and the formation of peroxynitrite may have an important role in the pathogenesis of recurrent tonsillitis.

Oral melanin pigmentation related to smoking in a Turkish population.

Besides genetic factors, tobacco smoking has been found to be the major cause of oral melanin pigmentation. The purpose of the present study was to evaluate the frequency of oral melanin pigmentation in a Turkish population and to present its correlation with clinical parameters relevant to periodontal status in current smokers, non-smokers, former smokers. A sample of 496 patients was randomly selected. The subjects were interviewed regarding their smoking habits. They were clinically examined by a single examiner for the presence of oral melanin pigmentation in different oral mucosal regions. The same examiner recorded the clinical parameters including GI (gingival index), PI (plaque index), BOP (bleeding on probing), PD (probing depth) and GR (gingival recession). Examiner 2 completed a questionnaire concerning skin color and smoking habits. In the study group, 41% were current smokers, 46% nonsmokers and 13% former smokers. The frequencies of pigmented areas were significantly higher in current smokers than in those without any smoking habits. The clinical parameters revealed similar findings for all groups. Low GI and BOP values were observed for current smokers when compared with non-smokers and former smokers, respectively. GI values were significantly associated with the pigmentations in gingiva. The results of our study show that smokers in a Turkish population had significantly more pigmented oral surfaces than nonsmokers.

Compensatory increases in cardiac output and SMA blood flows prevent splanchnic hypoperfusion during moderate isovolemic hemodilution in dogs

Intraoperative acute isovolemic hemodilution has been used to decrease the need for homologous blood transfusion. Decreased arterial oxygen content and total oxygen delivery to tissues promote a compensatory increase in cardiac output, related to the hemodilution-induced decrease in viscosity and/or vasodilatation, preserving tissue oxygen delivery. Regional blood flow distribution may vary widely between and within organs. Splanchnic hypoperfusion, particularly at the intestinal mucosal region, has been implicated in systemic inflammatory response and multiple organ dysfunction. We evaluated systemic and splanchnic oxygen-derived variables during a moderate acute isovolemic hemodilution to test the hypothesis that hemodilution may promote gastric mucosal acidosis, despite an apparent adequacy of global markers of oxygen delivery and consumption.

Hemangiopericytoma of the buccal region: A case report

Hemangiopericytoma is an uncommon mesenchymal tumor that represents 1% of all vascular neoplasms.1 In a study by Enzinger and Smith,2 16% of these tumors occurred in the head and neck area, with the nasal cavity and paranasal sinuses as the most common sites of involvement.3 Hemangiopericytomas may be benign, malignant, or may occur in an intermediate form characterized by unpredictable biologic behavior. In some cases, the malignant nature of an individual hemangiopericytoma is established only when the tumor recurs or metastasizes. We report an unusual case of a hemangiopericytoma that arose in the buccal mucosal region.

Expression of homeobox gene CDX2 precedes CDX1 during the transition from atrophic gastritis to intestinal metaplasia

mucosal region. Bcl-2 expression was unreactive in all tumor lesions. The mean follow-up period was 36.8 months (SD= 45.5), varying from 3 to 144 months. Three patients were lost of follow-up. Survival of patients with p53 expression and high proliferative rate (Ki67) was significantly lower than that of negative patients (overall survival of 10.4 months vs. 111.06 months, p = 0.01). Conclusions: 1. p53 expression associated with high proliferative rate help to distinguish between type I and type III gastric carcinoid tumors, suggesting a biologically aggressive growth pattern in the sporadic carcinoid tumors; 2. These markers can be used as prognostic factors for ECL cell tumors.

Increased expression of IL-16 in inflammatory bowel disease

BACKGROUND Inflammatory bowel disease (IBD) is characterised by infiltration of inflamed mucosal regions with CD4+ T lymphocytes and other mononuclear cells. Interleukin (IL)-16 exerts a strong chemoattractant activity on CD4+...

Mechanisms underlying eosinophil trafficking and their relevance in vivo.

After their formation in the bone marrow, eosinophils circulate with a short half-life and are distributed throughout the body, especially in mucosal and sub-mucosal regions. Although a small amount of these cells are normally seen in healthy tissue, blood and tissue eosinophilia is a hallmark of helminthic and allergic diseases. The role of eosinophils in the normal physiology of mucosal tissues is not understood, but there is good evidence to demonstrate that these cells protect the host at least against some intestinal helminths, specially those with a lung cycle. In addition, there are now many data that support a role for eosinophils in the pathophysiology of allergic diseases, such as asthma. Because helminthic diseases have been largely controlled in developed countries, there has been much interest in the development of drugs which affect eosinophil migration and/or activation in the tissue and which may, thus, be useful in the treatment of allergic conditions. The understanding of the mechanisms controlling eosinophil trafficking and/or activation are essential in the development of anti-eosinophil-based therapeutic strategies. The present paper reviews aspects of eosinophil biology with emphasis on the role of eosinophils in parasitic infections and allergy, the basic mechanisms underlying the trafficking of eosinophils into tissue and how these can be modulated pharmacologically.

P21, Bax and Caspase-3 participate in the propagating mechanism of apoptosis in the human gastric epithelial cells

Background and Aims: Apoptosis can be defined as the cell death programmed inherently. Bcl-2 family proteins such as Bcl-2, Bax and Bak act as preventive or promotive factors for apoptosis. Caspases are located in the common pathway to apoptosis, and act as the executors of apoptosis. Apoptosis is also closely related to the cell cycle, so that p21, a cyclin dependent kinase inhibitor, is also implicated in apoptotic process. In the human gastric mucosa, it is known that apoptotic cell death is upregulated relating to Helicobacter pylori (HP) infection, and the disintegration of apoptotic system, which excludes damaged cells may lead to carcinogenesis. However, it is unclear how apoptotic signals propagate in the human gastric mucosa.Therefore, we studied the apoptotic pathway in the human gastric mucosa. Materials and Methods: Gastric mucosal specimens were obtained from 10 HP-negative dyspepsia patients, 10 HP-positive chronic gastritis patients before and after HP eradication. Immunohistochemistry of Ki-67, p21, Caspase-3, Bax and Bak was performed and apoptotic cells were detected by the TUNEL method. Results: Ki-67 immunoreactivity was identified in the nuclei of proliferative cells located in the mucosal neck region, and the number of Ki-67 positive cells increased in HP positive gastric mucosa. Immunoreactivity of p21 was detected in the nuclei of the cells located in the area of more luminal than the cell proliferation area toward the mucosal surface. Immunoreactivities of caspase-3 and Bax increased in the cytoplasm and nuclei of the cells that were located predominantly in the upper part of surface mucosa. Bak did not show any remarkable changes. TUNEL positive cells were predominantly found at the tip of mucosa. The cells positive for p21 were also sporadically observed in the gastric gland, but they did not coincided with the caspase-3or Bax-positive cells. The expression of all these molecules was increased in the HP positive gastric mucosa and was decreased after HP eradication. Conclusions: The present data suggested that apoptotic signal may propagate in the gastric surface epithelium through the upregulation of p21, Bax and caspase-3 in both the normal and inflamed gastric surface mucosa, which would be set in just after cell proliferation. On the other hand, apoptosis in the gastric glandular cells might be regulated by different mechanisms from the surface epithelium.

Unknown primary head and neck squamous cell carcinoma: molecular identification of the site of origin.

Unknown primary head and neck squamous cell carcinoma (HNSCC) presents as a cervical lymph node metastasis without identification of the primary tumor, despite thorough diagnostic work-up that includes physical examination, computed tomography, esophagoscopy, laryngoscopy, bronchoscopy, and multiple surveillance biopsies. We investigated whether the site of origin of the primary tumor could be localized in the upper aerodigestive tract mucosa by detection of genetic alterations identical to those found in metastatic lesions. Microsatellite analysis was performed on metastatic tumors obtained from 18 patients with unknown primary HNSCC. Histologically benign surveillance biopsy specimens were also analyzed. Patients were followed up to 13 years with continuing surveillance for primary mucosal tumors. Most patients were treated with neck dissection followed by radiation therapy to the affected neck and ipsilateral Waldeyer's ring. In 10 (55%) of the 18 patients, at least one histopathologically benign mucosal biopsy specimen from defined anatomic sites (i.e., most likely sites for an occult primary tumor) demonstrated a pattern of genetic alterations identical to that present in cervical lymph node metastases. One patient harboring genetic alterations in the base of the tongue and two patients harboring genetic alterations in a tonsillar fossa subsequently developed HNSCC in the identical or adjacent mucosal region; all three of the primary head and neck mucosal tumors that eventually appeared between 1 and 13 years later in these patients had genetic changes identical to those in the benign mucosal biopsy specimens and in the metastatic lymph nodes. These data support the hypothesis that histopathologically benign mucosa of the upper aerodigestive tract may harbor foci of clonal, preneoplastic cells that are genetically related to metastatic HNSCC and that such mucosal sites are the sites of origin of unknown primary HNSCC. Microsatellite analysis may represent a clinically useful tool for determining such sites.

Effects of diets differing in propensity to promote gastric lesions on defense systems in gastric mucosae.

The objectives were to characterize biochemical changes, focusing on the antioxidant defense system, in stratified squamous and oxyntic mucosae in pigs fed diets with differing propensity to promote gastric lesions. Barrows (n = 24; 48.7+/-1.0 kg BW) housed in individual pens were used in the experiment. Barrows were fed a corn-soybean meal diet. Half of the animals were fed the diet as a coarsely ground meal (CGM; average particle size = 886 microm), and half were fed the diet as a finely ground pelleted (FGP; average particle size = 528 microm) feed. Initiation and termination of the experiment were staggered over a 3-wk period. Diets were fed for 6 wk. Visual evaluation of the stratified squamous mucosa of the proximal stomach showed increased (P<.001) damage in animals fed the FGP diet. These results were supported by histological evaluation. Thiobarbituric acid-reacting substances (TBARS), indicative of peroxide generation, relative to amount of protein were higher (P<.001) in stratified squamous than in oxyntic mucosa, and, per unit of tissue, TBARS were highest in stratified squamous mucosa of animals fed the FGP diet. Glutathione peroxidase activity followed a pattern similar to that of peroxides. Prostaglandin E2 was higher (P<.004) in stratified squamous than in oxyntic mucosa. In contrast, the activity of catalase was higher (P<.001) in oxyntic mucosa and was not affected by diet. The data show differences in the production of peroxides, the antioxidant defense system, and PGE2 between stratified squamous and oxyntic mucosae. Generation of prooxidants and the antioxidant defense system may play a role in the predilection of ulcers for the stratified squamous mucosal region of the pig stomach.

Activation and localization of transcription factor, nuclear factor-kappaB, in asthma.

Asthma is associated with increased expression of inflammatory proteins including cytokines, enzymes, and adhesion molecules. Induction of many of the genes for these proteins is regulated by the transcription factor, nuclear factor-kappaB (NF-kappaB). We therefore examined whether airway cells from patients with asthma show increased activation of NF-kappaB. Nuclear proteins were extracted from cells of induced sputum and from bronchial biopsies of normal subjects and patients with asthma. NF-kappaB-binding to its consensus DNA binding site, as investigated with 32P-labeled oligonucleotides and electrophoretic-mobility-shift assay, showed a 2.5-fold increase (p < 0.003) in NF-kappaB-DNA binding in induced sputum of asthma patients. Nuclear staining, representing activated NF-kappaB, was observed in macrophages of induced sputum. Immunohistochemical examination of bronchial biopsy specimens with an antibody to p65, a constituent of NF-kappaB, showed more airway epithelial cells with nuclear staining in asthma patients (45.1 +/- 7.2% versus 20.7 +/- 3.9%; n = 9; p < 0.01), and a 2.5-fold greater number of cells with cytoplasmic staining in the mucosal region (p < 0.05). Pooled nuclear extracts of bronchial biopsy specimens from asthma patients showed a 44% greater level of NF-kappaB-DNA binding. Activation of NF-kappaB may be the basis for increased expression of many inflammatory genes and for the perpetuation of chronic airway inflammation in asthma.

The expression of MMP-2 and TIMP-2 in patients with colorectal adenocarcinoma invaded to the submucosal and proper muscle layer.

The expression of MMP-2 and TIMP-2 was examined immunohistochemically in a total of 87 colorectal cancer patients. The expression of MMP-2 was in cancer cells: 76.5% (sm), 16.7% (pm), in cancer interstitial region: 92.2% (sm), 58.3% (pm), in transitional mucosal cells: 74.3% (sm), 17.1% (pm) and in transitional mucosal interstitial region: 80.0% (sm), 31.4% (pm). The expression of TIMP-2 was in cancer cells: 41.2% (sm), 16.7% (pm), in cancer interstitial region: 82.4% (sm), 69.4% (pm), in transitional mucosal cells: 57.1% (sm), 22.9% (pm) and in transitional mucosal interstitial region: 89.3% (sm), 57.1% (pm). These results suggest that the expression of MMP-2 and TIMP-2 is induced in the sm cancer stage and is closely related to interactions in the cancer interstitial region for invasion and metastasis in patients with colorectal adenocarcinoma.

Immunity, infection, and nasal disease.

Mucosal surfaces provide interfaces between the external and internal environments through which gases, nutrients, waste products, and other materials move. The properties of host mucosal surfaces that allow for these functions also provide ideal sites for the entry of microbial pathogens. Probably for this reason, the immune system developed defensive components with functions specialized for mucosal areas. These include mucus and its constituents, secretory immunoglobulins, and unique subsets of leukocytes that localize to or maturate in mucosal regions. They function to prevent attachment of microbes to host tissues and thereby prevent entry, and to signal and mobilize other immune components if entry has been achieved.

Treatment of Rats with Dexamethasone or Thyroxine Reverses Zinc Deficiency-Induced Intestinal Damage ,

Structural and functional damage to the intestine and the potential beneficial effects of dexamethasone (Dex) and thyroxine (T4) were examined in zinc-deficient rats. Rats were assigned to zinc deficient (ZD), control (C) or pair-fed (PF ) groups and fed for 40 d a zinc deficient (1 mg/kg) diet (ZD rats) or a similar diet supplemented with 50 mg Zn/kg (C and PF rats). Some rats of the ZD group were treated for the last 10 d with low (250 mg/kg) or high (5 mg/kg) doses of Dex or with T4 (100 mg/kg). Serum corticosterone of T4-treated ZD rats did not differ from untreated ZD rats. Serum T4 of T4-treated ZD rats did not differ from C rats. ZD rats developed ulcerations, inflammation and edema in the small intestine, particularly in the jejunum. PF rats did not show mucosal changes relative to C rats. ZD rats showed significantly lower crypt cell production rate (CCPR) and labeling index (LI) in the three intestinal regions, and lower cell migration rate and higher turnover time in the duodenum relative to C rats. Sucrase and maltase activities of ZD rats were significantly lower than C rats in the three mucosal regions. Treatment with the low dose of Dex resulted in fewer ulcerations compared with ZD rats. In rats administered the high dose of Dex or T4, all morphological alterations disappeared; the CCPR, LI, cell migration rate, cell turnover time and disaccharidase activities did not differ from C rats. In conclusion, Dex and T4 exert beneficial effects on zinc deficiency-induced intestinal alterations in rats.

ＳＤＭ（Ｓｃｈｌｅｉｍｈａｕｔｄｉｃｋｅｎ‐Ｍｅβｇｅｒａｅｔ）による粘膜厚径の検討 第１報 有歯顎者における口蓋粘膜

In order to clarify the reliability of measurement accuracy of the SDM apparatus, thickness of 9 palatine mucosal regions of 2 normo-dentulous subjects was determined and its correlation with the measured values for the same regions by puncturing was examined. Furthermore, thickness measurement was made of 10 palatine mucosal regions of 25 males and 11 females. The results were as follows:1. Intra-individual change in the measured value tended to be smaller by SDM method than by puncturing.2. A high correlation was noted between the measured values of palatine mucosal thickness diameter by puncturing and SDM method.3. As for the palatine mucosal thickness by SDM method:1) Palatine median region and retropalatine lateral region showed the smallest and the greatest thicknesses, respectively.2) Males tended to have greater thickness in all regions that were measured than females.

Nerve growth factor receptor and neurochemical markers in human oral mucosa: an immunohistochemical study.

The innervation of the oral mucosa has so far been studied mainly by histochemical and ultrastructural techniques. Only few studies have investigated the presence of neural proteins and neurotransmitters in human gingival mucosa. The purpose of the present study was to evaluate the presence and distribution of neural structural and transmitter proteins in different areas of normal human oral mucosa. Indirect immunofluorescence was employed on specimens taken from different mucosal regions (gingiva, lips, gums, palate). Both structural (low-affinity nerve growth factor receptor, NGFr; protein gene product 9.5, PGP 9.5) and neuropeptide markers (substance P; calcitonin gene-related peptide; vasoactive intestinal peptide, neuropeptide Y) were used. NGFr and PGP 9.5 intensely labelled both nerve fibres and selected epithelial cells, while neuropeptide immunoreactivity was scarcely expressed and exclusively localized in nerve fibres. Similarly in the distribution pattern and neurochemistry between oral and cutaneous innervation is apparent. Expression of NGFr could be relevant to the trophism of both the oral innervation and epithelium.