The nutrition transition in the Venezuelan Amazonia: increased overweight and obesity with transculturation.

OBJECTIVES: Amerindians have a particularly high propensity to overweight and obesity as they change lifestyle and experience a nutrition transition. The aim of this study was to evaluate the effects of transculturation on nutritional status in three Amazonian Amerindian villages. METHODS: Nutritional status was assessed in 232 volunteers: 65 Yanomami from an isolated village and 167 Guahibo subjects from villages with intermediate and high levels of transculturation. RESULTS: There was a significant pattern of decreasing stunting and increasing overweight and obesity across the gradient of transculturation. From the jungle Yanomami to the intermediate and transculturated Guahibo, stunting was respectively 72, 55, and 39%, and children /adult overweight was 0, 3/44, and 15/89%. These anthropometric-based patterns were confirmed by bioimpedance vector analysis. CONCLUSIONS: Transculturation in these Amerindian populations is associated with an increase in overweight and obesity coexisting with undernourished children.

A primary adrenal non-Hodgkin's lymphoma presenting as an incidental adrenal mass.

The primary adrenal localization of a non-Hodgkin's lymphoma (NHL) is a rare event. We report the case of a 70-yr-old woman, who was admitted at our Institute for a hormonal evaluation after the incidental discovery of a right adrenal mass during ultrasonography (US) performed for cardiovascular disease. At the physical examination, no sign of adrenal hyperfunction was present. She showed only an androgenetic alopecia and her blood pressure was 180/70 mm Hg, with an arrhythmic heart rate of 100 beats/min. No alterations in hormonal and biochemical data were observed. US studies showed a right adrenal mass (major diameter 16 mm), and an abdominal computed tomography (CT) scan confirmed this solid lesion (major diameter 15 mm) with a high density. [75Se] methylnorcholesterol adrenal scintigraphy exhibited a normal symmetrical radiotracer uptake. After 8 months of follow-up, an abdominal CT scan demonstrated a significant increase of the right adrenal mass (major diameter: 40 mm), with a solid tissue density and enhancement after i.v. contrast. [75Se] methylnorcholesterol adrenal scintigraphy showed an absent uptake on the right side versus the contralateral side. The hematological, hormonal and radiological evaluation did not reveal any sign of malignancy. Owing to the mass enlargement and the modification of scintigraphic pattern, the patient underwent unilateral adrenalectomy. Histological examination revealed a primary diffuse large B-cell NHL (REAL classification) of the adrenal gland. After surgery, she underwent a combined polychemotherapy (cyclophospamide, adriamycin, vincristine and prednisone) and subsequently one cycle of radiotherapy. At present, the patient is in good conditions and there are no signs or symptoms of recurrent disease.

Clinical relevance of expression of the CIP/KIP cell-cycle inhibitors p21 and p27 in laryngeal cancer.

PURPOSE: To investigate the prognostic relevance of p21 and p27 protein expression in laryngeal squamous cell carcinoma (LSCC). PATIENTS AND METHODS: We have analyzed by immunohistochemistry p21 and p27 expression in a series of 132 patients who underwent surgical resection of their LSCC and who had previously been investigated for p53 gene mutations and cyclin D1 expression. The tumors were considered low expressors when they had

Clinical relevance of cyclin D1 protein overexpression in laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic relevance of cyclin D1 gene overexpression in laryngeal squamous cell carcinomas (LSCCs). PATIENTS AND METHODS: The overexpression of cyclin D1 was analyzed in 149 LSCC patients with a median follow-up duration of 60 months using the DCS6 monoclonal antibody; only cases that overexpressed cyclin D1 in more than 5% of neoplastic cells were considered positive. RESULTS: Forty-eight cases (32.2%) were immunoreactive to the DCS6 antibody. Cyclin D1 overexpression was significantly associated with tobacco smoking and alcohol consumption, tumor extension, advanced clinical stage, and the presence of lymph node metastases. Univariate analysis showed that a shorter disease-free and overall survival were significantly associated with supraglottic site, tumor extension, advanced clinical stage, and cyclin D1 overexpression. At multivariate analysis, tumor extension and cyclin D1 overexpression were significantly associated with tumor recurrence, whereas tumor extension, supraglottic site and, at a borderline level of statistical significance, cyclin D1 overexpression, were associated with reduced overall survival. CONCLUSION: The overexpression of cyclin D1 in LSCC is associated with unfavorable clinicopathologic features and represents an independent significant predictor of laryngeal carcinoma prognosis, particularly for disease-free survival. This indicates that cyclin D1 evaluation may be a further useful element for selecting subgroups of patients who should be treated with more aggressive therapies.

Gastrin (G) cells are the cellular site of the gastric thyrotropin-releasing hormone in human fetuses and newborns. A chromatographic, radioimmunological, and immunocytochemical study.

In this study we analyzed the ontogeny and location of gastric TRH in human fetuses, preterm and term newborns, and adults. TRH immunoreactive cells were found in the antrum towards the bottom of developing glands and double immunostaining demonstrated that this neuropeptide is coexpressed with gastrin in the same cell (G-cell). In the youngest fetuses studied (12 weeks) G cells were few and contained both gastrin and TRH. They increased in number during development and were most abundant between 26 and 36 weeks of gestation. These morphological data correlated with total immunoreactive TRH content extracted from the whole stomachs of six fetuses and two preterm infants. On the contrary G cells containing both hormones were decreased in the newborn at term and not identified in the adult whereas those containing only gastrin were numerous in both. The TRH extracted was indistinguishable from synthetic TRH using chromatographic, radioimmunologic, and enzymatic criteria. As has already been reported, TRH was found in insulin-containing cells of the islets of Langerhans in the pancreas of our fetuses and newborns. These cells presented a similar development pattern to the gastric G cells.

Complement-mediated binding of immunoglobulins to some endocrine cells of the pancreas and gut.

Unspecific binding of immunoglobulins to gastrin, somatostain and glucagon cells of the gastrointestinal mucosa or pancreas has been found to occur through a nonantigen-antibody mechanism mediated by the C14 fraction of complement. The phenomenon represents an important drawback in hormone immunohistochemistry, which can be overcome by using complement deprived, highly dilute anti-hormone sera.

On the immunocytochemical localization of the vasoactive intestinal polypeptide.

The distribution of vasoactive intestinal polypeptide (VIP) immunoreactive nerves and endocrine cells in the gastrointestinal tract and pancreas of a number of mammalian and submammalian species has been examined in order to throw light on the exact localization of this peptide. Seven out of 8 VIP antisera demonstrated numerous nerve fibers in the gut, whereas one antiserum (TR2) revealed only scattered, few nerve fibers. The distribution of endocrine cells demonstrated by the different VIP antisera varied considerably. Thus, some antisera demonstrated only endocrine cells in the feline antrum, others only colonic endocrine cells and still others only endocrine cells of the upper gut and pancreas. The variability in staining pattern of endocrine cells as well as recent radioimmunological data makes it opportune to suggest that true VIP is a neuronal peptide and that endocrine cells store peptides resembling, but not being identical with, VIP (VIPoids).

p53 and cyclin D1 protein expression in glottic laryngeal squamous cell carcinomas involving the anterior commissure (pT1bN0M0).

The prognosis of patients carrying glottic squamous cell carcinomas (GSCCs) involving the anterior commissure is often unpredictable. In order to assess the possible prognostic role of new and reliable parameters, p53 and cyclin D1 protein expression was immunohistochemically analysed in pathological samples from 27 patients with GSCG (pTlbNOMO) and a median follow-up of 90 months. p53 protein expression was observed in the majority of patients (15/27), but it did not correlate with their clinical outcome; p53 protein immunoreactivity was frequently observed in normal (9/14), mildy dysplastic (10/14) and highly dysplastic (3/7) mucosa samples, suggesting that its overexpression may be involved in the earliest phases of the multistep tumourigenesis of laryngeal squamous cell carcinomas (LSCCs); neither the non-neoplastic nor the neoplastic samples expressed any cyclin D1. As cyclin D1 protein expression has been associated with a high frequency of nodal metastases, its absence in our series could ba related to the rarity of nodal involvement in early glottic LSCCs.

Three-step immunoscintigraphy with anti-chromogranin A monoclonal antibody in tumours of the pituitary region.

In the present paper we evaluated the ability of pretargeted immunoscintigraphy (ISG) with antichromogranin A (CgA) monoclonal antibody (Mc-ab A11) in visualizing pituitary masses. The results obtained in 23 patients are described along with those of [111In]pentetreotide scintigraphy (Octreoscan) in 18 cases. Positive ISG was obtained in 9/11 (82%) non-functioning, 1/4 growth hormone-, 1/2 prolactin-, 1/2 thyrotropin-, 1/1 follicle-stimulating hormone-, 0/1 adrenocortico-trophin-secreting pituitary adenomas. In one patient with a positive ISG scan of a non-functioning pituitary adenoma, an associated neurinoma of the acoustic nerve was not imaged. The same occurred in one patient with a pituitary deposit from a mammary carcinoma and in another one with a cyst of the Rathke's pouch. Chromogranin A immunohistochemistry, carried out in 10 tumours, was positive in eight pituitary adenomas and negative in two non-adenomatous lesions. A concordant ISG occurred in all cases except for two pituitary adenomas: one cystic and necrotized and one post-operative remnant very small in size. In 18 patients with pituitary adenoma both ISG and Octreoscan were positive in 61% of cases but with a different distribution among tumours. At variance with ISG, Octreoscan visualized only 5/10 (50%) non-functioning pituitary adenomas and all (4/4) somatotropinomas. In conclusion, ISG is able to image pituitary tumours and particularly non-functioning pituitary adenomas. In this respect, it may be helpful in discriminating non-neuroendocrine masses of the pituitary region from non-functioning pituitary adenomas.

Production of basic fibroblast growth factor by gastric carcinoid tumors and their putative cells of origin.

Using immunohistochemical techniques a subpopulation of endocrine cells in the human oxyntic mucosa was found to react with antibodies against basic fibroblast growth factor (bFGF). These cells were identified as histamine-producing enterochromaffin-like (ECL) cells and, to a minor extent, serotonin-producing enterochromaffin cells. Basic fibroblast growth factor immunoreactive cells were most frequently found in hyperplastic lesions of ECL cells occurring in hypergastrinemic patients (20 of 27 cases) and in ECL cell carcinoid tumors (10 of 17 cases). In addition, bFGF mRNA was demonstrated by Northern blot analysis of homogenates from two gastric carcinoids cytologically characterized as pure ECL cell tumors. Although the function of bFGF in normal cells remains unknown, its production in neoplastic conditions may be responsible for the associated desmoplastic and angioblastic proliferations. Moreover, secretion of bFGF by hyperplastic or neoplastic ECL cells may contribute to the circulating levels of the bFGF-like mitogenic factor identified in patients affected by multiple endocrine neoplasia type 1 syndrome.

The prevalence and clinical significance of chromogranin A and secretogranin II immunoreactivity in colorectal adenocarcinomas.

Colorectal adenocarcinomas may display features of endocrine differentiation, shown by argyrophil stains and by the expression of endocrine markers such as chromogranin A. We investigated chromogranin A and secretogranin II immunoreactivity in a series of 208 carcinomas of the large bowel to assess the prevalence and clinical significance of endocrine differentiation. Tumors expressing endocrine markers were classified as low expressors (< than 1 immunoreactive tumour cell/mm2) and high expressors (> than 1 immunoreactive tumour cell/mm2). There were 33 (16%) carcinomas showing both chromogranin A and secretogranin II immunoreactivity: 11 tumours (5%) were high expressors. Endocrine differentiation was not related to the disease stage, tumour location, grade, DNA ploidy and p53 protein accumulation. In the entire series chromogranin A immunoreactivity did not provide prognostic information using univariate and multivariate analysis. A worse overall survival (P = 0.048) was demonstrated for the stage III patients with high expressor tumours, but there were only five patients in this group. The results of our investigation suggest that chromogranin A immunoreactivity is not a useful variable in the prognostic assessment of colorectal adenocarcinomas.

Polysialylated N-CAM, chromogranin A and B, and secretogranin II in neuroendocrine tumours of the lung.

Highly alpha 2-8-sialylated N-CAM (neural cell adhesion molecule) impairs N-CAM-mediated cell adhesion. We investigated polysiaN-CAM immunoreactivity in a range of neuroendocrine lung tumours: 15 typical carcinoids, 21 atypical carcinoids, 2 large cell neuroendocrine carcinomas and 12 small cell lung carcinomas were selected on a morphological basis and by their immunoreactivity for chromogranin A and B and secretogranin II. A progressive loss of chromogranin expression, particularly of chromogranin B, was paralleled by the up-regulation of polysiaN-CAM in histologically more aggressive tumours (P = 0.001). These data support the hypothesis that loss of cell-cell adhesion properties might be a relevant factor in the origin of the aggressivity of lung neuroendocrine tumours.

Tryptophyllin-like immunoreactivity in rat adenohypophysis.

A new amphibian peptide family has been isolated from the skin of a South American frog Phyllomedusa rhodei and named Tryptophyllins (TPH) because of their content in tryptophyl residue. Using an antiserum against one of these peptides, namely the pentapeptide Met-5-TPH-5-amide (PHE-PRO-PRO-TRP-MET-NH2), we observed the presence of a set of immunoreactive cells in rat adenohypophysis. These cells were far more numerous in pregnant than in normal male and non-pregnant female rats. Dual immunostainings demonstrated that, with some exceptions, almost all the TPH-like immunoreactive cells were gonadotrophs. At electron microscope both types of gonadotroph cells displayed immunoreactivity and the gold particles strongly labelled both types of granules. The Aa. advance the hypothesis that, besides the hormones themselves, the secretory granules might contain some TPH-like sequence.

Gastric endocrine cells: types, function and growth.

The history of gastric endocrine cells identification and functional characterization is briefly outlined. An up to date classification of such cells is given. Present status of histopathological, histochemical, ultrastructural and molecular investigations on gastric endocrine hyperplasia and neoplasia is summarized and briefly discussed.

Immunodetection of secretogranin II in animal and human tissues by new monoclonal antibodies.

Secretogranin II (chromogranin C) is an acidic tyrosine-sulfated secretory protein, known to be a marker of neuroendocrine secretory products and of specific neuroendocrine tumours. In order to obtain anti-secretogranin II monoclonal antibodies for cell biology studies and, in particular, for clinical applications, we immunized mice with a secretogranin II-enriched fraction prepared from homogenates of bovine anterior pituitaries. Hybridoma supernatants obtained from the splenocytes of a hyperimmune mouse, screened with an enzyme-linked immunosorbent assay, were analyzed by both immunocytochemistry and two-dimensional immunoblotting. By using this experimental approach, we were able to identify two monoclonal antibodies (8G1 and 5A7) which recognize bovine secretogranin II. Both immunocytochemistry and immunoblotting revealed that one of them, the 5A7 antibody, cross-reacts with the human antigen. The distribution patterns of the immunoreactivity, obtained by immunocytochemistry with the 5A7 antibody in animal and human tissues, partially overlap those, obtained by using a polyclonal antiserum elicited against bovine secretogranin II, previously described. Moreover, the 5A7, but not the polyclonal antibody, reacts with some duodeno-jejunal cells. In conclusion, both the 5A7 and 8G1 antibodies can be useful for cell biology studies. The 5A7 antibody can be used for the detection of secretogranin II in human tissues and should be of help in clinical and pathological practices.

Lymph node micrometastases in patients with adenocarcinoma of the esophagogastric junction.

Recurrences of adenocarcinoma of the esophagogastric junction are frequent even in patients who are classified as pN0 after radical resection, suggesting that occult nodal metastases may have been missed on routine histologic examination. Immunohistochemical analysis using antibodies to cytokeratin was retrospectively performed in 1301 lymph nodes from 46 patients who underwent surgical resection for adenocarcinoma of the esophagogastric junction through a laparotomy and a right thoracotomy. Compared to routinely stained sections, the total number of metastatic lymph nodes was significantly (P = 0.0001) increased when both serial sectioning and anticytokeratin immunohistochemical analysis were performed. Overall 6 (33.3%) of the 18 patients previously considered N0 were recategorized as N1 for the presence of micrometastases to lesser curvature nodes. Three of these patients had recurrent disease within the first year of follow-up. Both the probability of survival or no recurrence and the disease-free survival were significantly greater in patients in whom the ratio of invaded to removed lymph nodes was less than 0.2. Anticytokeratin analysis identified occult nodal metastases in one third of our patients with adenocarcinoma of the esophagogastric junction. This modified tumor staging and had an impact on overall and disease-free survival.

p53 and cyclinX D1 protein expression in carcinomas of the parotid gland.

BACKGROUND: p53 and cyclin D1 genes play a central role in the regulation of the G1 phase of the cell-cycle, and are frequently involved in head and neck tumorigenesis. MATERIALS AND METHODS: By means of immunohistochemistry, we retrospectively investigated the overexpression of cyclin D1 and p53 genes in a series of 28 parotid gland carcinomas. The immunohistochemical analysis was performed using the ABC method and the antibodies DCS6 (for cyclin D1) and CM1 (for p53). RESULTS: p53 was overexpressed in 12 (42.9%) and cyclin D1 in 6 cases (21.4%). No significant association was found between p53 or cyclin D1 expression and the evaluated clinicopathological parameters of tumor extension, clinical stage, and lymph node or distant metastases. Nevertheless, it is worth noting that all of the patients with a high expression of p53 died of their disease. CONCLUSIONS: The present data confirm the role of p53 abnormalities in the pathogenesis of salivary gland carcinoma and report, for the first time, the involvement of cyclin D1 gene in these tumors.

Immunohistochemical and molecular analysis of bax, bcl-2 and p53 genes in laryngeal squamous cell carcinomas.

BACKGROUND: We investigated the role of apoptosis and its potential alterations in laryngeal squamous cell carcinomas (LSCCs) by evaluating bax, bcl-2 and p53 protein expression in 50 cases and by characterising the molecular status of the bax and p53 genes. MATERIAL AND METHODS: p53 and bax gene mutations were investigated by means of PCR/SSCP and direct DNA sequencing, and bax, bcl-2 and p53 protein expression by means of immunohistochemistry. RESULTS: We identified p53 gene mutations in 17/50 cases (34%); p53 expression in 26 of the 50 cases (52%); bcl-2 expression in 5/50 cases (10%); bax expression in 32/47 cases (68%). 18/33 cases with a wild type p53 gene overexpressed p53 protein: 12 cases (approximately 66%) were bax+/bcl-2-. Of the remaining cases without p53 protein expression, seven cases (approximately 47%) were bax+/bcl-2-. CONCLUSIONS: Our observations suggest that the overexpression of p53 may contribute to the repression of bcl-2 and the induction of bax expression in LSCCs. However, the fact that a number of cases not expressing p53 did not present any clear up-regulation of bax or down-regulation of bcl-2 suggests that bcl-2 and bax may be regulated by various mechanisms other than p53.

Ontogeny, distribution and amine/peptide colocalization of chromogranin A- and B-immunoreactive cells in the chicken gizzard and antrum.

The ontogeny and the distribution of chromogranin A (CgA)- and chromogranin B (CgB)-immunoreactive endocrine cells was studied in the chicken gizzard and gizzard-duodenal junction (also called pylorus or antrum) during embryonic and postnatal life. The same tissue sections were then double-immunostained to identify the CgA-and CgB-immunoreactive cells, with a panel of polyclonal antibodies raised against main gut amine/peptides. In the gizzard, positive cells were observed only in its two diverticula (proximal and distal caeca), where the first CgA- and CgB-immunoreactive cells were found on day 12 of incubation. They always remained moderate in number and co-stored mainly serotonin, gastrin/CCK and neurotensin. A few also co-stored somatostatin, but only during the embryonic period. Others co-stored PYY, but only after hatching. Co-localization with motilin was rare and never occurred with bombesin. In the chicken antrum, the first CgA- and CgB-immunoreactive cells were observed on day 12 of incubation and soon reached very high numbers. Antral positive cells showed almost the same co-localization pattern as the gizzard diverticula. Despite their high chromogranin content, the antral cells had weak argyrophilia, whereas in the gizzard diverticula the two staining patterns corresponded.