Search PubMed⌕ Search

Biomedical subjects

M Marcinkiewicz

Publications and source records attributed to M Marcinkiewicz.

At least 55 records · Page 3Linked to original sources
PubMed1996

The relationship between the content of aggressive and protective components in gastric juice and endoscopic findings after naproxen sodium and acetaminophen administration.

OBJECTIVES: To evaluate the diagnostic value of residual gastric juice, we assessed various secretory components before and after placebo, acetaminophen, or naproxen sodium administration. METHODS: In a double-blind, randomized, cross-over study in 30 asymptomatic volunteers, mucin, hydrophobicity, protein, pepsin, and pH were measured in residual gastric juice before and after placebo, naproxen sodium (660 mg/d), or acetaminophen (4000 mg/d) administration. Mucus layer thickness in biopsy specimens was assessed, and mucosal damage was endoscopically evaluated. RESULTS: All parameters were unchanged after 7 days of placebo. Naproxen caused a 46% (p = 0.008) increase in the rate of luminal mucin release, an 18% increase (p = 0.510) in protein release, and a 61% decrease (p = 0.001) in hydrophobicity. Antral and duodenal mucus gel thickness were compromised, and hemorrhagic and erosive endoscopic changes were noted. Acetaminophen resulted only in a significant decline of pepsin. In subjects without endoscopic damage after naproxen, a nonsignificant decrease in hydrophobicity was noted. However, in subjects with endoscopic changes, a 55% decrease (p = 0.002) in hydrophobicity and a 42% increase (p = 0.024) in the rate of luminal mucin release were demonstrated. The initial mucin of subjects who developed endoscopic mucosal changes after naproxen was 53% higher than in subjects without damage. Subjects with endoscopic changes also exhibited a 48% lower initial hydrophobicity and a 43% lower pepsin than subjects without endoscopic changes. CONCLUSIONS: Gastric mucosal damage after naproxen sodium results in profound changes within the gastric mucosal barrier, and analysis of residual gastric juice components adequately reflects these changes. In contrast, acetaminophen results in only minimal gastric juice changes. Analysis of residual gastric juice may be useful in monitoring the extent of mucosal damage and identifying patients likely to develop mucosal damage.

Acetaminophen↗
PubMed1996

Prostaglandin E2 content in residual gastric juice reflects endoscopic damage to the gastric mucosa after naproxen sodium administration.

OBJECTIVES: The diagnostic potential of residual gastric juice for development of naproxen sodium-induced mucosal damage has not been explored. We studied prostaglandin E2 (PGE2) content in residual gastric juice before and after naproxen sodium administration and assessed relationships with endoscopic mucosal damage. METHODS: Thirty volunteers received the recommended over-the-counter dose (660 mg/day) of naproxen sodium or placebo in this 7-day, double-blind, endoscopically controlled, cross-over study. RESULTS: PGE2 concentration in gastric juice did not increase after placebo; naproxen significantly reduced PGE2 concentration (p < 0.001). In three subjects in whom no endoscopic changes occurred after naproxen administration, PGE2 concentration increased by 14%. In seven subjects who developed hemorrhagic changes, PGE2 concentration declined by 50% (p = 0.08). In 20 subjects who developed numerous hemorrhagic and erosive changes within the antral mucosa, PGE2 concentration declined by 70% (p < 0.001). The starting PGE2 value in subjects with severe mucosal hemorrhagic and erosive changes after naproxen was almost eightfold higher than in subjects who did not develop mucosal damage (p = 0.007) and 67% higher than in subjects with hemorrhagic changes only (p = 0.25). CONCLUSION: PGE2 measurement in residual gastric juice, aspirated before and after nonsteroidal antiinflammatory drug treatment, may be useful in monitoring mucosal damage and may identify patients who are likely to develop endoscopic mucosal changes.

Adult↗
PubMed1995

Maintained PC1 and PC2 expression in the AtT-20 variant cell line 6T3 lacking regulated secretion and POMC: restored POMC expression and regulated secretion after cAMP treatment.

Two variant cell lines were recently established from parent AtT-20 cells. Whereas HYA.15.10.T.2 have a reduced level of secretory granules, HYA.15.6.T.3 are completely devoid of both the regulated pathway of secretion and of dense-core secretory granules. AtT-20 cells normally express the processing enzymes PC1, PC2, furin, carboxypeptidase E, and peptidylglycine alpha-amidating monooxygenase, as well as proopiomelanocortin, chromogranin B, and 7B2. We measured the expression of these mRNAs in both variant cell lines. Although some differences in mRNA level were noted, HYA.15.10.T.2 and HYA.15.6.T.3 cell lines maintained their expression of the processing enzymes and of 7B2. Furthermore, PC1 and PC2 were shown to be functionally active in the HYA.15.6.T.3 cells. In contrast, proopiomelanocortin and chromogranin B mRNA levels were no longer detectable in HYA.15.6.T.3 cells. Interestingly, stimulation of the HYA.15.6.T.3 cells with cAMP restored proopiomelanocortin mRNA, beta-endorphin immunoreactivity, and dense-core granules. Furthermore, at the ultrastructural level, beta-lipotropin immunoreactivity was detected in granules of cAMP-induced HYA.15.6.T.3 cells. Finally, depolarization of cAMP-induced HYA.15.6.T.3 cells with 56 mM potassium chloride resulted in a marked increase in the release of beta-endorphin immunoreactivity. These observations demonstrate that cAMP restores the regulated pathway of secretion in HYA.15.6.T.3 cells, which under untreated conditions do not demonstrate regulated release. These variant cell lines are unique models to understand better the relationship of the regulated pathway and the expression of the processing enzymes.

Animals↗
PubMed1995

Monophasic luminal release of prostaglandin E2 in patients with reflux esophagitis under the impact of acid and acid/pepsin solutions. Its potential pathogenetic significance.

Normal human esophageal mucosa exhibits biphasic secretory responses to intraluminal stimuli in terms of PGE2 release with a decline under the impact of HCl and an increase in PGE2 release during mucosal exposure to HCl/Pepsin. PGE2 secretory patterns in patients with reflux esophagitis (RE) remain unknown. We have studied, therefore, luminal release of PGE2 in 28 patients with nonhealed and healed RE, and compared the obtained results with corresponding values recorded in controls. The rate of luminal release of PGE2 in nonhealed RE exhibited a monophasic patterns, i.e., significantly decreased both during mucosal exposure to HCl (2,273 +/- 444, vs. 3,655 +/- 600 pg/min, p = 0.025) and HCl/pepsin (1,271 +/- 244, vs. 3,655 +/- 600 pg/min. p = 0.003) as compared to its basal value. However, the rate of luminal PGE2 release in patients with nonhealed RE in basal conditions and during mucosal exposure to HCl was significantly higher than corresponding values in controls. Luminal release of PGE2 in patients with healed endoscopic esophagitis was significantly lower as compared to corresponding values recorded in patients with nonhealed endoscopic changes and in controls. In conclusion, (a) monophasic inhibitory responses of the esophageal mucosa to intraluminal HCl and HCl/pepsin solutions in patients with RE indicate a different pattern of mucosal secretory response to intraluminal stimuli; (b) inhibition of the rate of luminal release of PGE2 under the impact of HCl/pepsin may play a role in the development and/or progression of mucosal damage; and (c) the decline in the rate of luminal PGE2 release in healed RE indicates that its elevated value in active esophageal disease should be considered as an implication of mucosal damage induced by HCl/pepsin.

Adult↗
PubMed1995

Modulatory impact of acid and pepsin on esophageal hydrophobicity in humans.

OBJECTIVES: The role of hydrophobicity in the pathophysiology of the gastrointestinal tract is well established as a protective mechanism against the impact of lumenal acid and pepsin. Hydrophobic properties of esophageal secretion in humans remain largely unknown. METHODS: We have studied, therefore, hydrophobicity by using fluorescence probe in human esophageal secretion, elaborated under the impact of saline followed by HCl, HCl/pepsin, and final saline. RESULTS: Basal hydrophobicity of human esophageal secretion, elaborated during mucosal exposure to saline, was 237 +/- 32. This value, however, declined 72% during mucosal exposure to HCl (66 +/- 14 vs 237 +/- 32; p < 0.001) and 87% during mucosal exposure to acid supplemented with pepsin (30 +/- 4 vs 237 +/- 32; p < 0.001). Moreover, hydrophobicity upon perfusion with HCl/pepsin was 55% lower than after perfusion with HCl alone (30 +/- 4 vs 66 +/- 14), although the result was insignificant. Substitution of saline for HCl/pepsin solution during the last perfusion period resulted in a partial recovery of hydrophobicity in esophageal secretion (131 +/- 30 vs 30 +/- 4; p < 0.001), although this value was lower than the basal hydrophobicity value (131 +/- 30 vs 237 +/- 32; p = 0.028). In addition, we continuously observed a significant shift in the fluorescence emission maximum from 508 +/- 6.4 to 486 +/- 0.9 (p < 0.001) during perfusion with starting saline, to 492 +/- 1.6 (p < 0.001) during exposure to HCl, to 493 +/- 1.1 (p < 0.001) during perfusion with HCl/pepsin, and to 488 +/- 0.9 (p < 0.001) during infusion of final saline. The maximum emission wavelength after esophageal exposure to initial saline also was significantly lower than the maximum emission upon perfusion with HCl (492 +/- 1.6 vs 486 +/- 0.9; p < 0.05) and HCl/pepsin (493 +/- 1.1 vs 486 +/- 0.9; p < 0.05). Although basal hydrophobicity in males was similar to corresponding values recorded in females, mucosal exposure to HCl (pH 2.1) resulted in an 84% decline in females but only 60% in males. Therefore, the hydrophobicity value in females during the perfusion period with HCl was 52% lower than in males (p = 0.129). CONCLUSIONS: Esophageal secretion exhibits its hydrophobic nature presumably through the presence of mucus components such as mucin and mucin-associated phospholipids. The inhibitory impact of HCl and HCl/pepsin solutions on esophageal hydrophobicity may play a role in the pathogenesis of mucosal damage by gastroesophagel refluxate.

Adult↗
PubMed1995

Mucosal adenosine deaminase activity and stump ulcer healing.

Adenosine deaminase activity was studied in endoscopically taken slices from gastric mucosa in patient after partial gastric resection performed due to complicated duodenal ulcer, and currently with peptic ulcer in the stump. The samples of gastric mucosa were taken before and after 6 weeks of treatment with ranitidine, 150 mg twice daily, at a distance within 2 cm and greater than 2 cm from the ulcer crater. Adenosine deaminase activity was measured in mucosa homogenates by determination of ammonia liberated from substrate. It was found that therapy with ranitidine was accompanied by an increase in enzyme activity in the mucosa surrounding unhealed stump ulcers, while no changes were noted in mucosa around healed stump ulcers. A possible role of mucosal adenosine deaminase activity in stump ulcer healing is postulated.

Adenosine Deaminase↗
PubMed1995

Distinct mRNA expression of the highly homologous convertases PC5 and PACE4 in the rat brain and pituitary.

Posttranslational endoproteolysis is essential for the production of biologically active peptides from inactive precursors. Six kexin/substilisin-like endoproteases have been characterized in mammalian species. To understand the complex physiological functions of each convertase within a cellular context it is necessary to comprehensively define its tissue distribution and cohabitation with other members of the family. Previous studies demonstrated the distinct distribution of PC1, PC2, and furin mRNAs in the pituitary and brain, suggesting a unique function for each enzyme. In the present study, the mRNA tissue distributions of the two most recent and homologous members, PC5 and PACE4, were analyzed in rat pituitary and brain using in situ hybridization histochemistry. In the pituitary, the anterior lobe exhibited moderate levels of PC5 and high levels of PACE4 mRNAs. The intermediate lobe showed low levels of PC5 expression, while PACE4 mRNA levels were undetectable. PACE4 transcripts were detected throughout cells of the neural lobe suggesting expression in pituicytes. In the brain, PC5 expression was more restricted than PACE4. PC5 mRNA was detected only in neuronal cells, whereas PACE4 mRNA was expressed in both neuronal and glial cells. In areas that are rich in neuropeptides such as cortex, hippocampus, and hypothalamus, mRNA levels of PC5 were high but PACE4 were low or undetectable. In regions, such as the amygdaloid body and thalamus, distinct but complementary distributions of PC5 and PACE4 mRNAs were observed. The medial habenular and cerebellar Purkinje cells expressed very high levels of PACE4 mRNA. The present data strongly suggest unique tissue-specific functions of PC5 and PACE4.

Animals↗
PubMed1994

Pan-neuronal mRNA expression of the secretory polypeptide 7B2.

The polypeptide 7B2 exhibits a widespread distribution in the CNS and in the endocrine tissues. By in situ hybridization in the mouse tissues, we detected 7B2-mRNA transcripts in most, if not all, neurons of the brain and spinal cord, and in the cranial and spinal ganglia. 7B2-mRNA was undetectable in supportive glial cells, ependymal cells and endothelial cells. In embryonic tissues, 7B2-mRNA expression was observed at midgestation, starting on day 11. Both differentiated neurons and neuronal precursors have been shown to express 7B2 transcript. We conclude that 7B2-mRNA is a good molecular marker of developing and definitive neurons.

Animals↗
PubMed1994

Adenosine deaminase activity in gastric cancer.

Adenosine deaminase activity, the key enzyme of adenosine inactivation, was studied in slices taken endoscopically from gastric cancer and macroscopically unchanged gastric mucosa surrounding the cancer. The activity of the enzyme was measured in mucosa homogenates by determination of ammonia liberated from substrate. It was found that adenosine deaminase activity in neoplastic lesions did not differ significantly from normal mucosa and that the gastric region studied (antrum, corpus) did not have an impact. A significant difference in enzyme activity was noticed between intestinal and diffuse-type gastric carcinoma (according to Lauren's classification); the intestinal type was characterized by lower adenosine deaminase activity than was the diffuse type. Since the activity of adenosine deaminase in gastric cancer did not exhibit significant differences from normal mucosa the diagnostic value of its determination is of less importance.

Adenosine Deaminase↗
PubMed1994

Declined human esophageal mucin secretion in patients with severe reflux esophagitis.

It has been recently demonstrated that human esophageal submucosal mucous glands exhibit the ability to secrete copious amounts of mucin, well known within the gastrointestinal tract for its protective quality against hydrogen ion and pepsin. Since mucin may also play a protective role within the esophageal compartment, we have studied the rate of secretion of esophageal mucin in patients with RE. Mucin was assessed by periodic acid-Schiff methodology in esophageal secretion collected during continuous perfusion with saline (period I) followed by HCl (period II), HCl/pepsin (period III), and final saline (period IV), mimicking the natural gastroesophageal scenario. The basal rate of the luminal release of mucin in patients with grade II RE was 18% lower as compared with controls. During exposure of the esophageal mucosa to an HCl/pepsin solution, esophageal mucin output in the RE group was 52% lower than in the control group (0.154 +/- 0.027 vs 0.320 +/- 0.049 mg/cm2/min; P = 0.025). Furthermore, the rates of esophageal mucin output in patients with grade III RE during esophageal perfusion with saline and HCl/pepsin were 62% (0.090 +/- 0.021 vs 0.239 +/- 0.036 mg/cm2/min; P = 0.016) and 86% (0.048 +/- 0.010 vs 0.320 +/- 0.049 mg/cm2/min; P = 0.001) lower when compared with corresponding values in controls. After endoscopic healing of RE, the overall impairment in the rate of esophageal mucin secretion in patients with grade II improved from 31% to 17% at the end of therapy, whereas in patients with grade III the impairment in mucin secretion improved only marginally from 71% to 69%.(ABSTRACT TRUNCATED AT 250 WORDS)

Catheterization↗
PubMed1994

The mouse homeoprotein mLIM-3 is expressed early in cells derived from the neuroepithelium and persists in adult pituitary.

LIM-homeodomain proteins are important in cell lineage specification and possibly mediate transcriptional processes in eukaryotes. During the screening of a mouse pituitary cDNA library, we isolated a partial cDNA coding for a novel gene product that exhibited a predicted amino-terminal sequence similar to the homeobox of LIM-homeodomain-containing proteins. Reverse transcriptase-polymerase chain reactions (RT-PCR) performed on mouse pituitary mRNA using degenerate oligonucleotides based on the conserved LIM-domain sequences, allowed the extension of the 5' end of the sequence. The composite 2.2-kb cDNA structure predicts a 400-amino-acid-long novel mouse (m) protein, called mLIM-3. This name was chosen since within the 59-amino-acid homeodomain, it exhibits 97% sequence identity to a recently reported Xenopus homologue xLIM-3. The gene coding for mLIM-3 maps to the murine chromosome 2, most probably within the 2B band. Based on sequence characteristics, we suggest that LIM-3 belongs to a distinct subfamily of LIM-containing homeoproteins. Ontogeny studies using in situ hybridization demonstrated that mLIM-3 transcripts can be detected on embryonic day 11 (e11) in the primordium of the hypophysis. Following a maximum between e12 and e14, lower levels persisted into adulthood, where mLIM-3 was expressed primarily in the anterior and intermediate lobes of the pituitary. These results were confirmed by Northern blot analysis in adult mice which revealed a 2.4-kb pituitary mRNA transcript. mLIM-3 transcripts were also detected in pituitary cell lines such as the somatotrophs GH3 and GH4C1, the gonadotroph alpha T3-1, and the corticotroph AtT-20 cells, but not in 20 other cell lines derived from peripheral, endocrine, and neural tissues. Starting from e11, we also observed a transient expression of mLIM-3 in the ventral part of the spinal cord, pons, and medulla oblongata, reaching a maximum at e13 and from p7 onward, the expression of this transcript is no longer detectable. mLIM-3 is also expressed in the pineal gland with high levels observed at e20. These data suggest a potential role for mLIM-3 in the transcriptional regulation of certain genes during morphogenesis and/or maintenance of the differentiated state of the pituitary, motor neurons, and pineal gland.

Amino Acid Sequence↗
PubMed1994

Developmental expression of the prohormone convertases PC1 and PC2 in mouse pancreatic islets.

The immunocytochemical distribution and messenger RNA expression of the prohormone convertases PC1 and PC2 involved in the posttranslational processing of precursor proteins were analyzed in mouse and rat pancreatic islets. Immunocytochemical colocalization studies demonstrated a close association of insulin with both PC1 and PC2 in the adult mouse and rat pancreas. The coexpression of insulin with the prohormone convertases was further examined in rat pancreatic tumors induced by streptozotocin-nicotinamide treatment. These insulin-synthesizing tumors expressed PC1 and PC2, whereas insulin-silent adenomas did not. Colocalization studies demonstrated that only PC2, not PC1, colocalizes with glucagon, pancreatic polypeptide, and somatostatin. The highest levels of PC2-like immunoreactivity were observed in the glucagon-containing alpha-cells. Ontogeny studies carried out by in situ hybridization in mice showed the first detectable expression of the prohormone convertases in the pancreatic primordium at midgestation, starting for PC1 on embryonic day 11 and for PC2 on embryonic day 10. Enzyme expression was further confirmed by immunocytochemistry, which detected the presence of immunoreactive PC1- and PC2-like proteins on embryonic days 14 and 17, respectively. Taken together, our data suggest that both PC1 and PC2 play a role in proinsulin processing in vivo, whereas PC2 is a likely candidate convertase participating in the processing of proglucagon, propancreatic polypeptide, and prosomatostatin in pancreatic islets.

Adenoma↗
PubMed1993

Mucosal adenosine deaminase activity and gastric ulcer healing.

Adenosine deaminase activity was studied in gastric corpus mucosa close to an ulcer crater. It was found that 6 weeks of therapy with ranitidine was accompanied by a decrease in enzyme activity in the mucosa around healed ulcers and an increase around those which failed to heal. The different activities of adenosine deaminase in the vicinity of healed and unhealed ulcers may indicate its possible role in peptic ulcer healing.

Adenosine Deaminase↗
PubMed1993

Ontogeny of the prohormone convertases PC1 and PC2 in the mouse hypophysis and their colocalization with corticotropin and alpha-melanotropin.

In the adult pituitary, anterior lobe corticotrophs and intermediate lobe melanotrophs differentially process proopiomelanocortin (POMC). Within the corticotrophs, POMC is processed mainly to corticotropin (ACTH) and beta-lipotropin, while alpha-melanotropin (alpha MSH) and beta-endorphin are the major end products in the melanotrophs. The observed transient presence of alpha MSH-like immunoreactivity during ontogeny suggested an age-dependent variation in POMC processing in the adenohypophysis. In this tissue, cell-specific POMC products are likely the result of differential expression of the two known prohormone convertases PC1 and PC2. In the present ontogeny study done in the mouse intermediate and anterior pituitary, we examined how the expression pattern of PC1 and PC2 mRNA transcripts correlates with that of ACTH and alpha MSH-like immunoreactivities. Our data demonstrated that both PC1 and PC2 transcripts can be detected in the presumptive adenohypophysis starting on embryonic day 15 (E15). In the intermediate lobe, PC1 and PC2 mRNAs appear on E18 and E16, respectively, and their levels increased during ontogeny, reaching maximal expression in the adult. Similarly, PC1 expression in the anterior pituitary increased from E15 to adulthood. However, PC2 mRNA expression peaked between postnatal days 1 (P1) and 14 (P14) and then decreased to adult levels. The distribution of PC1 and PC2 immunoreactivity is nicely correlated with the in situ hybridization data. In the anterior lobe, during the P1-P14 postnatal period, PC2 immunoreactivity was detected within cells synthesizing an alpha MSH-like peptide(s). This observation substantiates our earlier biochemical data suggesting that PC2 is the important convertase in the processing of POMC into alpha MSH. Furthermore, the demonstrated variation in the relative ratio of PC1/PC2 expression during ontogeny rationalizes the observed plasticity of POMC processing in the adenohypophysis. It is expected that beta-endorphin processing will follow that of alpha MSH.

Adrenocorticotropic Hormone↗
PubMed1993

Depolarizing action of secretory granule protein 7B2 on rat supraoptic neurosecretory neurons.

A novel precursor neuropeptide termed 7B2 is present within specific brain areas, including the hypothalamic magnocellular neurosecretory neurons, and appears to be processed to smaller fragments. In order to determine whether specific C-terminal fragments of 7B2 might exert local effects on neurosecretory cells, we used intracellular current-clamp recordings in supraoptic neurons maintained in superfused hypothalamic explants to evaluate membrane potential and resistance changes in 25 supraoptic nucleus neurons during bolus applications of 7B2 174-186 and two other C-terminal peptide fragments 7B2 156-173 and 7B2 141-150. In 15 supraoptic neurons, only the 7B2 174-186 fragment induced a gradual 2-8 mV membrane depolarization that lasted for 4 to 30 min and was accompanied by 15+/-8% reduction in input resistance. Immunocytochemical identification of the recorded cells revealed that both vasopressin (VP)- and oxytocin (OT)-containing neurons were depolarized by 7B2 174-186. These data suggest that 7B2 174-186 is a biologically active fragment of 7B2 and may regulate the excitability of magnocellular supraoptic nucleus neurons.

Animals↗