Re: Mucin gene expression in human urothelium and in intestinal segments transposed into the urinary tract.
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Biomedical subjects
Publications and source records attributed to F Aragona.
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We have investigated the direct effect of glucagon on collagenase-dispersed adrenocortical cells obtained from consenting patients undergoing unilateral adrenalectomy and nephrectomy for renal cancer. Dispersed cells, actually a mixture of zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells, were incubated with glucagon (from 10(-10) to 10(-6) M) alone or in the presence of 10(-9) M angiotensin-II, 10(-10) M ACTH or 10(-5) M forskolin, and the effects on aldosterone, cortisol and cyclic-AMP (cAMP) production were measured by radioimmune assay. Glucagon concentration-dependently inhibited ACTH-stimulated cortisol production and ACTH- or forskolin-enhanced cAMP release, minimal and maximal effective concentrations being 10(-9) and 10(-7) M. The effects of glucagon were suppressed by 10(-5) M Des-His1-[Glu9]glucagon amide, an antagonist of glucagon receptors (glucagon-A). Reverse transcription-polymerase chain reaction did not reveal the presence of specific glucagon-receptor mRNA in the human adrenal cortex. However, autoradiography demonstrated the presence of [125I]glucagon binding sites in the ZF/R, which were displaced by glucagon but not by ACTH. Taken together, these findings suggest that glucagon, through the activation of unidentified receptors located on ZF/R cells, inhibits adenylate cyclase, thereby dampening glucocorticoid response to ACTH.
Four cases of unexpected death due to acute myeloid leukemia have been studied: myeloblastic M1 (case I and II), promyelocytic M3 (case III), myelomonocytic M4 (case IV). Diagnosis was performed before death only in case III. Histological leukostasis was the most evident feature in all cases, particularly at the lung level, where tumor-like aspects were evident and widely diffused in case II. The last three cases were pregnant at the third trimester. Serious hemorrhagic complications were evident in all cases: CID in the former 3 cases and primary hyperfibrinolysis in the 4th, as demonstrated by the absence of intravascular cloths in many organs and especially in lung and kidney; abundant, on the contrary, in the former three cases. Leukostasis was not associated to hyper-leucocytosis in all 4 cases, but associated to normal number of peripheral white cells (below normal level in case III). This phenomenon, that disagrees with literature data on acute or chronic reactivated myeloid leukemia leukostasis, may be due to the primary confination of the immature granuloblasts in the vascular bed, because of the hemoreologic effects connected with their deficient plasticity, that is essential for normal granulocytes to flow easily in the capillary bed. In all cases death was caused by breathing and cardiocirculatory insufficiency with the associated unceasing hemorrhages.
AACOF3 is a trifluomethylketone analog of arachidonic acid, which inhibits phospholipase-A2 (PLA2). AACOCF3 was found to concentration-dependently increase basal aldosterone and corticosterone secretion by dispersed rat zona glomerulosa and zona fasciculata/reticularis cells, respectively, as well as aldosterone and cortisol production by dispersed human adrenocortical cells. Maximal effective concentration was 10(-5) M, and elicited about 2.5-3.0-fold rises in steroid output. 10(-5) M AACOCF3 also enhanced submaximally (10(-15)/10(-12) M), but not maximally (10(-9) M) ACTH-stimulated hormonal secretion. Quantitative HPLC showed that 10(-5) M AACOCF3 evokes similar increases (from 2.0- to 3.0-fold) in the basal release of the entire spectrum of adrenocortical steroids (i.e. both intermediate and definitive products of steroid synthesis), thereby suggesting that AACOCF3 acts on the early steps of steroid synthesis. Accordingly, when pregnenolone metabolism is prevented by cyanoketone, 10(-5) M AACOCF3 increased by about 8-10-fold the production of this steroid. In conclusion, we have demonstrated a side-effect of AACOCF3, which may become relevant in studies where this chemical is used to inhibit PLA2 in tissues able to convert cholesterol to pregnenolone.
Blood samples were collected intraoperatorily from inferior vena cava (VC) and adrenal vein (AV) of 8 male and 9 female consenting adult patients undergoing unilateral nephrectomy with ipsilateral adrenalectomy for kidney cancer, and steroid-hormone concentrations were assayed by quantitative HPLC. Hormonal concentrations were significantly higher in AV than in VC (systemic) blood and did not display significant differences between males and females. Higher levels not only of the main glucocorticoids cortisol and corticosterone, but also of their inactive oxidized forms corticosterone and 11-dehydrocorticosterone (DH-B), respectively, were detected in AV than in VC blood. Highly significant inverse correlations between cortisol and cortisone, and corticosterone and DH-B concentrations were observed in AV, but not in VC blood. Moreover, in AV blood the concentration of the main cortisol precursor 11-deoxycortisol correlated inversely with those of both cortisone and DH-B. Taken together, these findings are in keeping with previous in vitro evidence that human adrenal glands possess 11beta-hydroxysteroid dehydrogenase activity, which is engaged in the inactivation of newly formed glucocorticoids and is probably negatively regulated by the local concentrations of non-11beta-hydroxylated steroid-hormone precursors.
The development of a reno-jejunal fistula following a Roux-en-Y cystojejunostomy for an incorrectly diagnosed pancreatic pseudocyst is described. Up to now, this is the second case of iatrogenic reno-jejunal fistula reported in literature. Reno-jejunal fistulas are exceedingly rare and are usually consequences of urologic pathologies of infectious origin. Reno-jejunal fistulas of iatrogenic origin are even rarer, only one case being referred in literature [1]. Herein the second case is reported.
OBJECTIVE: Abdominal ultrasound has shown a frequent association between abdominal lymphadenopathy (LA) and chronic liver disease, but contradictory data have been reported on its relationship with the main parameters of hepatic function. The aim of this study was to correlate the prevalence of LA in patients who were chronic hepatitis-anti-hepatitis C virus positive prospectively followed-up over the last 3 years and its relationship with biochemical and histological data. METHODS: 136 RIBA II confirmed positive patients with ALT levels >2N were included. None of these had been or was at the time of study on interferon treatment. Ultrasound was performed using a Toshiba SSA 240 A apparatus with a 3.75 MHz convex probe; the operator was unaware of the other results. Diagnosis of chronic hepatitis in all cases was made on biopsy specimens; the histological activity index (HAI) score, according to Knodell, and the grading (G) and staging (S) scores, according to Desmet, were also evaluated. RESULTS: LA was found in 54 out of 136 patients (40%); accordingly, patients were divided into two groups: the LN + ve group included 54 patients (M 33, mean age 48.1+/-11.7 yr) and the LN-ve group included 82 patients (M 69, mean age 45.3+/-11.9 yr). LN + ve patients showed significantly higher serum levels of AST (p < 0.0005), ALT (p < 0.001), gammaGLO (p < 0.05) and gammaGT (p < 0.02) than LN - ve patients. There was a more severe degree of liver disease in LN + ve patients, expressed by the higher HAI (p < 0.002), G (p < 0.002), and S (p < 0.005). The chi2 test for linear association analysis confirmed the trend toward greater histological severity in LN + ve patients (chi2 MH = 10.2; p < 0.002). Logistic regression confirmed the association between the presence of LA and AST (p < 0.02), ALT (p < 0.03), G (p < 0.02), and S (p < 0.02). CONCLUSION: This study showed a moderate prevalence of LA in chronic hepatitis C, lower than that reported in other studies. LA was associated with serum parameters of cytolysis, and above all, with the severity of histological damage.
In gastric and colonic mucosa the abnormal pattern of mucin secretion has been related to an increased risk of malignant changes. The short- and long-term histologic and histochemical changes in the mucin content of the ileal mucosa have been studied in 180 biopsies from 90 male patients 6-96 months after radical cystectomy and urinary diversion via an orthotopic neobladder. Up to 3 years after surgery, histologic changes comprise a shortening of the villi and an increase in the number of goblet cells. Concomitantly, an abnormal pattern of mucin secretion, with a predominant secretion of sulfomucins, is demonstrable. After 3 years of follow-up, the mucosa progressively flattens and mucin production reduces; after 6 years, the prevalent finding is a flat, avillous epithelium without evidence of mucin secretion. There was no dysplasia or malignancies in any of the patients. The changes in the pattern of mucin production are not potential preneoplastic lesions, but represent a transient defence mechanism of the ileal mucosa exposed to urine.
OBJECTIVE: Measurement of the ethanol concentration in expired breath during transurethral resection of the prostate (TURP). METHODS: TURP is a noninvasive method to estimate the amount of irrigant absorbed. The expiratory breath ethanol concentrations (EBEC) were measured with a standard alcohol breath analyzer in 35 patients in the course of TURP. All interventions were performed with a 27-french continuous flow resectoscope using a solution of 1. 5% glycine + 1% ethanol as irrigating fluid. Serum sodium and osmolality were measured pre- and postoperatively. No patient developed signs of transurethral resection syndrome; no significant changes in serum sodium, osmolality and EBEC were found throughout the operation. CONCLUSION: Absorption of irrigant fluid during TURP with continuous low-pressure irrigation seems to be extremely slight (if not absent) as measured by expired breath ethanol method.
Proadrenomedullin N-terminal 20 peptide (PAMP) is a 20-amino acid hypotensive peptide expressed in the adrenal medulla. We investigated the localization and function of PAMP receptors in the human adrenal gland. Autoradiography showed the presence of [125I]PAMP-binding sites in both zona glomerulosa and adrenal medulla that were displaced by cold PAMP and PAMP(12-20) but not by other preproadrenomedullin-derived peptides. PAMP, but not PAMP(12-20), counteracted, in a concentration dependent manner, both aldosterone response of zona glomerulosa cells and catecholamine response of adrenal medulla cells to BAYK-8644, the selective agonist of voltage-activated Ca2+ channels, as well as to K+ and angiotensin II. PAMP(12-20) partially reversed this antisecretagogue effect of PAMP. Collectively, these findings suggest (1) that PAMP inhibits Ca2+-dependent, agonist-stimulated aldosterone and catecholamine secretion, acting via specific receptors and through a mechanism involving the impairment of Ca2+ influx; and (2) that PAMP(12-20) acts as a weak antagonist of PAMP receptors, thereby suggesting that both C- and N-terminal sequences of the PAMP molecule are required for this peptide to exert its antisecretagogue action on the human adrenal gland.
Cerebellin is a 16-amino acid peptide, originally isolated from rat cerebellum, whose presence has been recently demonstrated in the human adrenal glands and especially in medullary chromaffin cells. Cerebellin concentration dependently increased basal catecholamine (norepinephrine and epinephrine) release by human adrenal slices, containing medullary chromaffin tissue, minimal and maximal effective concentrations being 10(-9) and 10(-7) mol/L. Cerebellin (10(-7) mol/L) markedly enhanced cAMP release by adrenal slices, and the protein kinase A inhibitor H-89 (10(-5) mol/L) blocked catecholamine response to cerebellin. Cerebellin did not affect basal steroid secretion of dispersed human adrenocortical cells, but it concentration dependently increased aldosterone and cortisol production by adrenal slices. Again minimal and maximal effective concentrations were 10(-9) and 10(-7) mol/L. Aldosterone and cortisol responses to 10(-7) mol/L cerebellin was suppressed by both the beta-adrenoceptor antagonist l-alprenolol (10(-6) mol/L) and H-89 (10(-5) mol/L). Collectively, the present findings allow us to conclude that 1) cerebellin exerts a sizable secretagogue action on both cortex and medulla of human adrenals; 2) the peptide directly stimulates catecholamine release via the adenylate cyclase/protein kinase A-dependent signaling pathway; and 3) the mechanism underlying the adrenocortical stimulatory effect of cerebellin is indirect and probably involves the release of catecholamines, which in turn, acting in a paracrine manner, enhance steroid-hormone secretion.
The present article describes the observations and experiments of Bartolomeo Bizio on a typical food of northern Italy known as "polenta", corn flour boiled in water and salt, on which purpurine stains would appear at high temperature and moisture. Due to these experiments and investigative work, Bizio is considered to be the father of modern bacteriology and bacterial biochemistry.
Adenocarcinoma "not otherwise specified" of the larynx appears to be extremely rare. We report a case of adenocarcinoma "NOS" arising in the larynx of a 72 year-old white man. The neoplasia was ALCIAN and PAS negative. Immuno-histochemical studies revealed negative immunoreactivity from NSE, chromogranins and S100; cytokeratin was positive. Electron microscopy revealed electrodense granules of varying sizes, but with no obvious central core surrounded by a limiting membrane. The patient underwent a total laryngectomy and functional neck dissection, with mandibular extension. And he is free of tumor after 4 years postoperatively.
PURPOSE: The structure of the retroperitoneal connective tissue of the female pelvis was evaluated to determine whether its spatial arrangement may have a role in supporting the pelvic viscera. MATERIALS AND METHODS: After in situ formalin fixation the pelvic viscera with the surrounding connective tissue were removed together with the pelvic floor from 18 female cadavers 48 to 68 years old. Serial macrosections of the bladder base, cervix, lower rectum and pelvic floor complex, cut in coronal (4 cases) and horizontal (10 cases) planes, were stained with azan-Mallory, and the remaining 4 were cut in the horizontal plane and plastinated using von Hagens E12 technique. Morphometry of the retroperitoneal connective tissue was performed using a computerized system for image analysis connected through a black and white television camera to an optic microscope. The diameters of the adipose lobules and density of the connective tissue were evaluated in the proximity of the visceral adventitia and the parietal pelvic fascia, respectively. RESULTS: The retroperitoneal connective tissue of the female pelvis consists of varying amounts of adipose tissue divided into small lobules by thin connective laminae. These laminae are connected to the visceral and parietal layers of the pelvic fascia, and are closely connected to the vascular and nervous bundle sheaths crossing the pelvis. At the level of the sacrouterine and cardinal ligaments we were unable to find any connective ligamentous structure. Only an areolar tissue was seen, which after removal of the lipids demonstrated a fibrillar structure. The mean area of the adipose lobules was smaller (average of 1.41 mm.2) near the viscera with respect to the lateral retroperitoneal connective tissue (average of 1.73 mm.2) due to greater ramification of the connective laminae. CONCLUSIONS: In the absence of real connective ligaments the retroperitoneal connective tissue forms a 3-dimensional network of thin connective laminae that are connected to the visceral adventitia, parietal layer of the pelvic fascia and neurovascular bundles crossing the pelvis. These connective laminae are bounding adipose lobules of different size (smaller near the viscera, larger at the periphery). Overall, the retroperitoneal connective tissue constitutes an anatomical structure that, beyond the functional limits of any individual ligament, may have supporting properties.
BACKGROUND/AIMS: The indications for liver biopsy in anti-HCV-positive patients with persistently normal alanine aminotransferase levels are not clearly established. Recent studies have correlated the presence of abdominal lymphoadenomegaly with disease severity in patients with chronic hepatitis C. Our study aimed to evaluate the frequency of abdominal lymphoadenomegaly in an anti-HCV positive blood donor population with persistently normal alanine aminotransferase and the relationship of abdominal lymphoadenomegaly with the severity of liver changes. METHODS: Eighty-six anti-HCV positive blood donors (58 M, 28 F) with normal alanine aminotransferase were followed up for a median of 31 months (range 12-50). To evaluate the frequency of abdominal lymphoadenomegaly, all patients underwent ultrasound scan. The common parameters of liver function as well as serum HCV RNA levels were determined. Histological changes were evaluated both in a conventional manner and using the numerical scoring systems of Knodell and Desmet. RESULTS: Of the 86 donors, 68 (79%) maintained persistently normal alanine aminotransferase levels during follow-up, and abdominal lymphoadenomegaly was present in 15 of them (22.0%). The remaining 18 donors (21%) showed rises in alanine aminotransferase above normal levels during the follow-up and seven of them (38%) had abdominal lymphoadenomegaly (p=n.s.). In the subjects with normal alanine aminotransferase, there were no significant differences in the common parameters of liver function and the serum presence of HCV RNA between those with or without abdominal lymphoadenomegaly. Normal liver was found in five patients without abdominal lymphoadenomegaly, but never in patients with abdominal lymphoadenomegaly. Analysis with the Mantel-Haenszel test showed a trend toward more serious changes in patients with abdominal lymphoadenomegaly (chi-square MH=9.5, p<0.003). Histological changes did not differ when Knodell's score was used; in contrast, staging, evaluated by Desmet's score, and periportal necrosis were significantly higher in subjects with abdominal lymphoadenomegaly (p<0.01 and p<0.004, respectively). Multiple logistic regression showed a significant relation between histological changes and the presence in serum of HCV RNA (p<0.004) and gamma-globulin (p<0.002), and abdominal lymphoadenomegaly p<0.003). CONCLUSION: Our study shows a prevalence of 22.0% of abdominal lymphoadenomegaly in anti-HCV positive subjects with normal alanine aminotransferase values and a relationship with the degree of liver histology change. Therefore, we suggest that the evidence of abdominal lymphoadenomegaly in these patients could be an indication to perform liver biopsy.
OBJECTIVE: To investigate the long-term morphological changes in the intestinal segment used to create an orthotopic ileal neobladder. MATERIALS AND METHODS: Periodic endoscopy with biopsy of the ileal mucosa was performed in 90 patients 3-84 months after radical cystectomy and urinary diversion via an orthotopic neobladder. Three cold-cup biopsies were taken from each patient and mucosal specimens processed for light and electronic microscopy. RESULTS: Early changes (up to 1 year after surgery) comprised a marked shortening of the villi with loss of microvilli. After 4 years, the prevalent finding was of flat, avillous epithelium that tended to stratify in some areas. The avillous areas were mixed with islets of villous mucosa. There was no dysplasia or malignancy in any of the 90 patients. CONCLUSIONS: Prolonged contact with urine elicited a biphasic response in the ileal mucosa, i.e. an early inflammatory phase, ascribed to the noxious action of urine, followed by a regressive phase in which the epithelium tended to assume a morphology similar to the urothelium. The atrophic changes were almost totally completed after 4 years, although areas with marked modifications alternated with others where the morphology was normal, even many years after surgery. Late changes in the ileal neobladder mucosa appear to be an expression of a functional adaptation of the mucosa to the new environment.
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