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Biomedical subjects

G Rindi

Publications and source records attributed to G Rindi.

At least 55 records · Page 3Linked to original sources

A thiamine/H+ antiport mechanism for thiamine entry into brush border membrane vesicles from rat small intestine.

Outwardly oriented H+ gradients greatly enhanced thiamine transport rate in brush border membrane vesicles from duodenal and jejunal mucosa of adult Wistar rats. At a gradient pHin5:pHout7.5, thiamine uptake showed an overshoot, which at 15 sec was three times as large as the uptake observed in the absence of the gradient. Under the same conditions, the binding component of uptake accounted for only 10-13% of intravesicular transport. At the same gradient, the Km and Jmax values of the saturable component of the thiamine uptake curve after a 6 sec incubation time were 6.2 +/- 1.4 microM and 14.9 +/- 3 pmol.mg-1 protein.6 sec-1 respectively. These values were about 3 and 5 times higher, respectively, than those recorded in the absence of H+ gradient. The saturable component of the thiamine antiport had a stoichiometric thiamine: H+ ratio of 1:1 and was inhibited by thiamine analogues, guanidine, guanidine derivatives, inhibitors of the guanidine/H+ antiport, and imipramine. Conversely, the guanidine/H+ antiport was inhibited by unlabeled thiamine and thiamine analogues; omeprazole caused an approximately fourfold increase in thiamine transport rate. In the absence of H+ gradient, changes in transmembrane electrical potential did not affect thiamine uptake. At equilibrium, the percentage membrane-bound thiamine taken up was positively correlated with the pH of the incubation medium, and increased from about 10% at pH 5 to 99% at pH 9.

Animals↗

Cell biology, clinicopathological profile, and classification of gastro-enteropancreatic endocrine tumors.

Recent developments in the field of endocrine cell biology and pathology at both morphological and molecular levels are briefly outlined and discussed as a basis for endocrine tumor characterization. The main tools available for identifying the endocrine nature of the tumors, their pathogenetic interpretation. and experimental reproduction with special emphasis on tumor antecedents are reported. Based on this, classifications of endocrine tumors of the pancreas and gastrointestinal tract are developed, covering most clinical (hyperfunctional syndromes included), pathological, and biological patterns, with special emphasis on tumor prognosis.

Gastrointestinal Neoplasms↗

Thiamine pyrophosphate-dependent and thiamine metabolizing enzymes in the deafferented cerebellum and in the intact cerebral cortex of rat.

The effects of chemical (CD) and surgical (SD) deafferentation of the cerebellum on thiamine pyrophosphate (ThPP)- dependent enzymes (transketolase, TK; pyruvate-, PDH, and alpha-ketoglutarate, alphaKGDH, dehydrogenases) and thiamine (Th) metabolizing enzymes (thiamine pyrophosphokinase, ThPK; thiamine mono-, ThMPase, and pyrophosphatases, ThPPase) were evaluated in vitro in rats in steady state conditions. The enzymes were also determined in the intact cerebral cortex of the same animals. CD was carried out by i.p. injection of 3-acetylpyridine, followed by harmaline and niacinamide. SD was carried out by complete dissection of the peduncles of the left cerebellar hemisphere. Chemical and surgical cerebellar deafferentations significantly lowered the contents of both Th-metabolizing and ThPP-dependent enzymes in the cerebellum without modifying those of the cerebral cortex. ThPK and TK, which are particularly concentrated in neurons, were the most affected enzymes. The decrease in ThPP-dependent enzymes shown here is associated with the slowing down of the Th phosphorylation-dephosphorylation cycle and with no modification in the ThPP content in the cerebellum, both of which were found in a previous study. Cerebellar deafferentation seems to only affect the apoenzyme moiety of the enzymes.

Afferent Pathways↗

Colonic disease in cirrhotic patients with portal hypertension: an endoscopic and clinical evaluation.

Fifty cirrhotic patients with portal hypertension but without colonic or systemic disease underwent lower gastrointestinal endoscopy in order to investigate the effects, if any, of portal hypertension on the colon. Fifty patients without liver or systemic disease, examined by colonoscopy because of irritable bowel syndrome in the same period served as controls. Rectosigmoid varices were observed in 34% of the cirrhotic patients and 2% of the controls. Hemorrhoids were observed in 70% of the cirrhotic patients and 48% of the controls. Multiple vascular-appearing lesions were found in 16% of the cirrhotic patients and 6% of the controls. Nonspecific inflammatory changes were noted in 10% of the cirrhotic patients and 4% of the controls. Simultaneous presence, in the same patient, of rectosigmoid varices, hemorrhoids, multiple vascular-appearing lesions, and nonspecific inflammatory changes, was observed in only five (10%) of the cirrhotic patients. We found polyps in 12% of the cirrhotic patients and 14% of the controls, and a malignant tumor in 4% of the cirrhotic patients. The patients with normal colonoscopic findings were 8% of the cirrhotic patients and 36% of the controls. All patients and controls were followed up for 1 year; there was no gastrointestinal hemorrhage among controls, whereas 34% of the cirrhotic patients had an upper gastrointestinal hemorrhage (88% from esophageal varices, 12% from the stomach) and 4% had a lower gastrointestinal hemorrhage (one from rectosigmoid varices and one from nonspecific inflammatory lesions). Colonic lesions were significantly more frequent in the cirrhotic patients (92%) than in the control group (64%); however, such lesions did not seem specific to the disease and were not statistically correlated with the degree of esophageal varices by Child's grading, the etiology of cirrhosis, or the bleeding risk from the lower gastrointestinal tract.

Adult↗

The tumours of the endocrine pancreas.

Tumours of the endocrine pancreas are rare entities with evidence of endocrine cell differentiation. Immunohistochemistry is the most reliable method used to study such tumours either for the identification of their hormonal product(s) or to explore functional aspects like proliferative activity or oncoprotein overexpression (e.g. p53). Most of the endocrine tumours of the pancreas are well differentiated and behave as benign or low grade malignant tumours. Poorly differentiated (small cell) endocrine carcinomas are rare and have a poor prognosis.

Humans↗

Abnormal gastric histology and decreased acid production in cholecystokinin-B/gastrin receptor-deficient mice.

BACKGROUND & AIMS: The cholecystokinin (CCK)-B/gastrin receptor is one of several regulators of gastric acid secretion and mucosal growth. To elucidate the contribution of this receptor relative to other trophic and secretory factors, mice that lack the CCK-B/gastrin receptor have been generated and studied. METHODS: Both alleles of the CCK-B/gastrin receptor were inactivated by targeted gene disruption. Analysis of the mice included measurement of basal gastric pH and plasma gastrin levels. In addition, multiple gastric mucosal cell types were identified by immunostaining and quantified. RESULTS: Homozygous mutant mice were viable, fertile, and appeared grossly normal into adulthood. The receptor-deficient mice exhibited a marked increase in basal gastric pH (from 3.2 to 5.2) and an approximately 10-fold elevation in plasma gastrin concentration compared with wild-type controls. In the stomach of mutant animals, parietal and enterochromaffin-like cells were decreased, providing a likely explanation for the reduction in acid output. In the antrum, a decrease in somatostatin cell density and an increase in the gastrin cell number were observed, consistent with the concomitant elevation in circulating gastrin. CONCLUSIONS: Together, these findings demonstrate the importance of the CCK-B/gastrin receptor in maintaining the normal cellular composition and function of the gastric mucosa.

Animals↗

Thiamine uptake in human intestinal biopsy specimens, including observations from a patient with acute thiamine deficiency.

Mucosal biopsy specimens obtained by routine endoscopy from 108 human subjects, including one patient with thiamine deficiency, were incubated at 37 degrees C in oxygenated calcium-free Krebs-Ringer solution (pH 7.5) containing tritiated thiamine and [14C]dextran as a marker of adherent mucosal water. The amount of labeled thiamine taken up was measured radiometrically. In subjects with no clinical evidence of thiamine deficiency, 1) thiamine uptake by duodenal mucosa had a hyperbolic time course, reaching equilibrium at 10 min; 2) thiamine concentrations < 2.5 mumol/L were taken up predominantly by a saturable mechanism displaying Michaelis-Menten kinetics (K(m) 4.4 mumol/L and Jmax 2.3 pmol.mg wet tissue-1.6 min-1), whereas higher concentrations were taken up by passive diffusion; 3) thiamine transport had different capacities along the gastrointestinal tract (duodenum >> colon > stomach); and 4) thiamine uptake was competitively inhibited in the duodenum by thiamine analogs, albeit with a different order of potency compared with rats, and was blocked by 2,4-dinitrophenol. In the thiamine-deficient patient, the duodenal saturable uptake was increased, with higher K(m) and Jmax values. In conclusion, physiologic concentrations of thiamine were transported in human small intestine by a specific mechanism dependent on cellular metabolism, whose transporters appear to be down-regulated.

Adolescent↗

In vivo study of the kinetics of thiamine and its phosphoesters in the deafferented rat cerebellum.

The effects of chemical (CD) and surgical (SD) deafferentation of the cerebellum on different steps of the metabolism of thiamine (Th), thiamine monophosphate (ThMP) and thiamine pyrophosphate (ThPP) were evaluated in vivo in rats. CD was carried out by i.p. injection of 3-acetylpyridine, followed by harmaline and niacinamide. SD was carried out by complete dissection of the peduncles of the left cerebellar hemisphere. Under steady state condition the radioactivity of Th and its phosphoesters was determined in plasma and whole cerebellum after an i.p. injection of thiazole-[2(14)C]-thiamine (30 micrograms:1.25 micro Ci). Analytical data were processed by using an improved mathematical compartmental model, which allowed the calculation of fractional rate constants (FRC), turnover rates (TR) and turnover times (TT). Both CD and SD caused a significant reduction of TR values for Th phosphorylation to ThPP, dephosphorylation of ThPP to ThMP and Th, and ThMP, but not Th, release. TT for all Th compounds were increased compared to controls, indicating a general slowing of thiamine metabolism in the deafferented cerebellum. These results indicate an imbalance in the thiamine metabolism resulting from the impaired activity of cerebellar neurons. The possible implications of the changes in rate of Th compound turnover with respect to biochemical changes in cerebellar ataxia are discussed.

Afferent Pathways↗

Evaluation of clinical patterns in ulcerative colitis: a long-term follow-up.

The aim of this prospective research was to compare, in a seven-year follow-up, the clinical outcome of ulcerative pancolitis with that of non-progressive ulcerative colitis. The activity of the disease was evaluated by a Clinical Activity Index and an Endoscopic Index. Of 112 cases of ulcerative colitis observed, 95 showed no change in extent and were studied as examples of non-progressive UC, and in this group the extension of the disease was: pancolitis in 19%, left-sided colitis in 39%, proctosigmoiditis in 17% and proctitis in 25%. A colectomy had to be performed in 5%. None of the enrolled cases developed a cancer during the follow-up. The patients with ulcerative pancolitis or left-sided colitis were treated with 5-ASA 1.6 g/day in a delayed-release formulation, while the cases with proctosigmoiditis or proctitis were treated with 5-ASA enemas 4 g/day. The cases with more than one relapse/year were 39%. The proportion of patients with only one relapse/year was 53%. The patients with steady remission for all the seven years of the trial were only 8%, but with a statistically significant difference between the groups with initial diagnosis of proctosigmoiditis or proctitis and the group with initial diagnosis of pancolitis or left-sided colitis (12% versus 5%). Among the cases with continuous remission, 37% showed colonic alterations, with an endoscopic score higher than 4 but a clinical score less than 6. Side-effects were observed in 6% patients but without treatment withdrawal. Non-progressive ulcerative colitis throughout the colon has a relatively good prognosis which seems to be independent of the location of the disease, even if we have found a statistically significant higher percentage of cases with steady remission among the patients with more distal disease.

Administration, Oral↗

Prognostic criteria in nonfunctioning pancreatic endocrine tumours.

To identify prognostic subgroups among non-functioning (nonsyndromic) pancreatic endocrine tumours, a series of 61 tumours were analysed systematically for macroscopic, histopathological and immunohistochemical variables potentially predictive of malignancy. High-grade nuclear atypia, elevated mitotic rate and multifocal necrosis allowed us to separate 5 poorly differentiated carcinomas from 56 well differentiated tumours. Among the latter, 29 well-differentiated carcinomas showing gross local invasion or metastases were identified. Vascular or perineural microinvasion, Ki67 proliferative index > 2%, mitotic rate > or = 2, size > or = 4 cm, capsular penetration, nuclear atypia, lack of progesterone receptors and presence of calcitonin were among the variables correlated with malignancy. The first two were the most sensitive and specific. Their presence or absence was used in the 27 tumours lacking evidence of malignancy at the time of surgery to separate 11 cases with increased risk of malignancy (in 2 of which metastases developed during follow-up) from 16 cases with limited risk. The resulting four prognostic groups of non-functioning pancreatic endocrine tumours (limited- and increased-risk tumours, well-differentiated carcinomas and poorly differentiated carcinomas) showed distinct survival curves, which were significantly affected by vascular microinvasion, Ki67 proliferative index and metastases.

Adult↗

Gastric carcinoids and neuroendocrine carcinomas: pathogenesis, pathology, and behavior.

The goal of this study was to provide information of prognostic value for gastric endocrine tumors. A total of 205 gastric endocrine tumors have been studied: 193 well differentiated tumors [2 gastrin cell tumors, 191 enterochromaffin-like (ECL) cell tumors] and 12 poorly differentiated carcinomas. Subtyping of ECL cell tumors (carcinoids) resulted in 152 associated with chronic atrophic gastritis (CAG) (type 1); 12 associated with hypertrophic gastropathy (HG) due to Zollinger-Ellison syndrome with multiple endocrine neoplasia type I (type 2), and 27 with no specific association (type 3, sporadic). Type 1 cases occurred most often in female (108 of 152), elderly (mean 63 years) patients, with no tumor-related death at an overall mean follow-up of 53 months. The 12 type 2 cases were equally distributed between the sexes (six of each), with a mean age of 45 years; there was one tumor-related death (49 months after diagnosis) and an overall mean survival of 84 months. Type 3 cases were mostly in men (20 of 27), with a mean age of 55 years; there were seven tumor-related deaths at a mean follow-up of 28 months. Poorly differentiated neuroendocrine carcinomas were observed in elderly patients (mean 63 years, range 41-76 years) of both sexes, with nine tumor-related deaths and a mean survival of 7 months. It was concluded that correct clinicopathologic subtyping may predict the clinical behavior of gastric endocrine tumors.

Adult↗

Antral gastrin cell hyperfunction and Helicobacter pylori infection.

BACKGROUND: Antral gastrin cell hyperfunction (AGCH), is a rare cause of duodenal ulcer associated with non-tumour hypergastrinaemia and acid hypersecretion. AIM: To investigate the role of Helicobacter pylori in AGCH. PATIENTS: Twelve AGCH patients and eight H. pyloripositive non-hypergastrinaemic duodenal ulcer patients were compared. METHODS: Basal and peak acid outputs, gastrin-stimulation (meal and bombesin) tests, and immunohistochemistry for antral G and D cells were performed. One year after H. pylori eradication, six AGCH patients were again investigated with the same tests. RESULTS: Significantly more basal, and stimulated gastrin and acid secretion, were found in AGCH compared to the H. pylori-positive duodenal ulcer patients (P < 0.01). G cell counts were significantly higher in AGCH than in duodenal ulcer patients (118.8, range 58-192.4, vs. 86.1, range 49-184; P < 0.05), and the resulting G/D cell ratio was also higher in AGCH patients (4.2, range 2.6-5.6, vs. 3.3, range 1.9-4.3; P < 0.05). H. pylori was present in the gastric mucosa of all 12 AGCH patients. Cure of infection in six AGCH individuals resulted in marked a decrease of gastrin levels associated with a significant (23.7%: P < 0.05) decrease of G cell count and an increase (12%; P < 0.05) of D cell count. CONCLUSIONS: The results indicate that AGCH may result from H. pylori overstimulation of gastrin cell function in patients with some presently undefined, familial predisposition and that an imbalance of the G/D cell ratio may have a role in the genesis of hypergastrinaemia.

Adolescent↗

Peptide YY expression is an early event in colonic endocrine cell differentiation: evidence from normal and transgenic mice.

The hormone peptide YY is produced by endocrine cells in the pancreas, ileum and colon. We have previously shown that peptide YY is coexpressed in all four islet cell types in the murine pancreas when they first appear, suggesting a common peptide YY-producing progenitor. In the colon, peptide YY has been frequently identified in glucagon-expressing L-type endocrine cells. Characterization of colonic endocrine tumors in transgenic mice expressing simian virus 40 large T antigen under the control of the peptide YY gene 5' flanking region revealed tumor cells producing not only peptide YY and glucagon, but also neurotensin, cholecystokinin, substance P, serotonin, secretin, and gastrin. This suggested that multiple enteroendocrine lineages were related to peptide YY-producing cells. Subsequent examination of the ontogeny of colonic endocrine differentiation in nontransgenic mice revealed that peptide YY was the first hormone to appear during development, at embryonic day 15.5. Between embryonic days 16.5 and 18.5, cells expressing glucagon, cholecystokinin, substance P, serotonin, secretin, neurotensin, gastrin and somatostatin first appeared and peptide YY was coexpressed in each cell type at this time. Peptide YY coexpression continued in a significant fraction of most enteroendocrine cell types throughout fetal and postnatal development and into adulthood, with the exception of serotonin-producing cells. This latter population of cells expanded dramatically after birth with rare coexpression of peptide YY. These studies indicate that expression of peptide YY is an early event in colonic endocrine differentiation and support the existence of a common progenitor for all endocrine cells in the colon.

Animals↗

[Carcinoid tumors of the stomach in atrophic autoimmune gastritis: classification, differential diagnosis and prognosis].

With the aim of evaluating the prognosis of neuroendocrine tumours of the stomach we studied 255 patients with these tumours to gain informations about the different biological behaviour of these tumours. We examined subtypes on the basis of the type of gastritis according to RINDI et al. 1993. A classification was made on the basis of tumour size, depth of invasion, angio invasion, functioning or non functioning, metastatic or non metastatic according to CAPELLA et al. 1994 to estimate benign and low or high grade malignant behaviour. 191 carcinoid tumours in autoimmune gastritis were in 86.4% classified as benign tumours (88% not more than 1 cm in diameter, 1 case with lymph node metastasis, no carcinoid tumour related death). 12 carcinoids associated with ZES-MEN I showed a benign or low grade malignant behaviour (60% more than 1 cm in diameter, 2 cases with lymph node metastasis, 1 with distant metastasis, 1 carcinoid related death). 36 sporadic carcinoid tumours were in 42% low grade malignant (36% 1-2 cm size, 25% more than 2 cm in diameter, 3 cases with lymph node metastasis, 2 with distant, 6 with lymph node and distant, 7 carcinoid related death). 13 neuroendocrine carcinoma were high grade malignant (1.5-7 cm size, 6 cases with lymph node metastasis, 2 with distant, 4 with lymph node and distant, 8 carcinoma related death). Therefore we conclude that in the classifications compared carcinoid tumours in A-gastritis are-in contrast to the other types of neuroendocrine tumours of the stomach-benign tumours with a good prognosis. The type of gastritis is for the prognosis of gastric neuroendocrine tumours besides tumour size and metastasis the most important parameter.

Adolescent↗