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Biomedical subjects

J Polak

Publications and source records attributed to J Polak.

At least 19 recordsLinked to original sources
PubMed2000

Disorder-specific changes in innervation in oral lichen planus and lichenoid reactions.

The peripheral nervous system was analysed in the oral mucosa of eight patients with oral lichen planus (OLP), five with a lichenoid reaction (LR) and three with mild chronic inflammation (MCI), by morphometric analysis of nerve fibres containing immunoreactive PGP 9.5, substance P (SP), calcitonin gene-related peptide (CGRP), vasoactive intestinal polypeptide (VIP), or C-flanking peptide of neuropeptide Y (CPON). Overall nerve fibre density was higher in OLP (P=0.039) and LR (P=0.026) compared with healthy oral mucosa and was compatible with sprouting and collateral formation. In contrast to the innervation visualized with structural nerve fibre-marker PGP 9.5, the densities of neuropeptide-immunoreactive nerves were low in inflamed tissue. This is consistent with depletion via local release. Retraction and local loss of innervation were found in areas coinciding with the most severe inflammation and basal membrane (BM) damage. Interestingly, LR showed a twenty-eight-fold loss of post-ganglionic CPON-ir sympathetic nerve fibres (P=0.044). In LR, CPON-ir innervation was markedly lower than in OLP. Finally, the pattern of innervation in relation to inflammatory cell infiltrates and tissue structures differed between OLP and LR. In conclusion, the peripheral nervous system is implicated in the immunopathogenesis of lichen planus and lichenoid reactions, with a disorder-specific difference in this involvement.

Adult↗
PubMed2000

Time-dependent sensory nerve ingrowth into a bone conduction chamber.

We studied time-dependent ingrowth of sensory nerve fibers into a bone defect in a rat bone conduction chamber model. In 10 male Sprague Dawley rats, a titanium chamber was implanted bilaterally in the proximal tibiae, representing an experimental bone defect. To mimic a clinical situation, the chambers were filled with a fresh blood clot After 1, 2, 4, 6 and 8 weeks, 2 rats were fixed in vivo at each time before removal of specimens, and histological and immunohistochemical analyses. We used antisera against protein gene product 9.5, neural growth-associated protein 43/B-50, calcitonin gene-related peptide, and substance P, to locate regenerating sensory nerve fibers in the chamber. During bone defect healing, hematoxylin/eosin sections showed that new bone grew in through the ingrowth openings in the chamber, gradually filling it and replacing the blood clot. At 1 and 2 weeks after implantation, no nerve fibers could be detected. At 4, 6 and 8 weeks, however, small numbers of nerve fibers were seen in 8 of 11 specimens. The nerve fibers were located mainly in the dense fibrous tissue in close proximity to the new bone, and in some cases within the new forming bone. In this chamber model, the periosteum is not in contact with the bone ingrowth openings, and all ingrowing nerve fibers thus originated from the cortical bone, endosteum or bone marrow. We speculated that these late ingrowing sensory nerve fibers may actively participate in bone repair.

Animals↗
PubMed1999

Protection against aspirin-induced human gastric mucosal injury by bosentan, a new endothelin-1 receptor antagonist.

BACKGROUND: Gastric ulceration induced by aspirin and by non-steroidal anti-inflammatory drugs (NSAIDs) is a major clinical problem. The mechanism of injury is unclear. There is evidence that NSAID-induced injury may cause endothelin activation. Endothelin-induced vasoconstriction has been shown to be capable of causing gastric ulceration. AIM: To investigate whether acute gastroduodenal injury induced in humans by aspirin can be prevented by the endothelin-1 antagonist, bosentan. METHODS: Eighteen healthy volunteers each received 5 x 900 mg aspirin every 12 h on three separate occasions (with either placebo, bosentan 700 mg or misoprostol 400 mg). Treatment order was randomized by Latin square design. Subjects were endoscoped and erosions counted before and 90 min after the first and last dose of aspirin. Plasma concentrations of bosentan were measured up to 5 h post-dose. RESULTS: There was a significant reduction in the mean number of erosions in the aspirin plus bosentan and aspirin plus misoprostol groups after the first dose of aspirin, compared with controls (aspirin plus placebo) (P<0.05). This was not sustained after the fifth dose of aspirin in the aspirin plus placebo and aspirin plus bosentan groups, but was still present in the aspirin plus misoprostol group. The mean plasma concentration of bosentan measured 3.5 h post-dose fell from 4510 (95% CI: 2791-6230) ng/mL after the 1st dose to 2508 (95% CI: 1733-3283) ng/mL after the 5th dose (P = 0.02). CONCLUSION: Endothelin receptor antagonism by bosentan can protect the gastric mucosa against aspirin damage. After five doses, bosentan levels fell, possibly because of enzyme induction, and protection was no longer evident. Further investigation is needed to assess whether higher doses would be effective.

Adult↗
PubMed1999

[Clinical observations concerning piracetam treatment of patients after craniocerebral injury].

Piracetam (Nootropil) is a cytoprotective to brain tissue and improving cerebral blood flow medicine. In the Department of Neurotraumatology we investigated results of piracetam treatment in a group of 100 succeeding patients admitted between 1995-96 due to craniocerebral injury. High doses (24-30 g per day) of this medicine have a positive effect on final result of treatment, when treatment is initiated immediately after the injury and described conditions are abided. We also showed usefulness of piracetam treatment in posthospital management.

Brain Injuries↗
PubMed1998

The role of lipopolysaccharide, pro-inflammatory cytokines and bacterial superantigens in the transcriptional regulation of lymphotoxin alpha and beta in mouse splenocytes.

Lymphotoxin alpha (LT-alpha) and lymphotoxin beta (LT-beta) are members of the tumour necrosis factor (TNF) ligand family. Because of the importance of TNF in the pathogenesis of septic shock, the expression of LT-alpha and LT-beta mRNA in murine splenocytes stimulated with different pro-inflammatory cytokines, sepsis-associated mediators such as lipopolysaccharide (LPS) and bacterial superantigens was investigated. The authors show that the bacterial superantigens, toxic shock syndrome toxin 1 (TSST-1) and staphylococcal enterotoxin B (SEB) upregulate LT-alpha mRNA expression in vitro in murine cells. Basal expression of LT-beta mRNA was found in unstimulated murine splenocytes, and could be increased by the addition of the mitogen concanavalin A (Con A). Despite this suggested inducibility of the murine LT-beta transcript, sepsis-associated mediators did not affect its regulation. Neither the pro-inflammatory cytokines interleukin 2 (IL-2), TNF-alpha nor LPS alone or in combination with interferon gamma (IFN-gamma) had any effect on LT-beta mRNA expression. The bacterial superantigens TSST-1, SEB and streptococcal pyrogenic exotoxin A (SPEA) were also unable to upregulate LT-beta mRNA transcript, in contrast to the observation with LT-alpha.

Aging↗
PubMed1998

In vitro accommodation of porcine endothelial cells by low dose human anti-pig antibody: reduced binding of human lymphocytes by accommodated cells associated with increased nitric oxide production.

Transplanted xenografts, protected from rejection by depletion of xenoreactive natural antibodies (XNA) and complement, can sometimes survive when complement levels and titres of anti-graft antibodies return to baseline; this phenomenon is called accommodation. We have previously reported that low concentrations of human IgG induce a change in the phenotype of immortalised porcine endothelial cells (IPEC) consistent with the development of accommodation. The cells acquired a resistance to lysis by human complement and showed a reduced expression of VCAM. In this study, we extend these findings by showing that VCAM expression falls on several IPEC clones and on primary porcine endothelial cells. Moreover, we show that these accommodated cells bind fewer human lymphocytes compared to controls, implying that leukocyte traffic through accommodated endothelium may be altered compared to that through normal endothelium. Finally we show that during the induction of accommodation, porcine endothelial cells produce greater amounts of nitric oxide than controls, due to the expression of inducible nitric oxide synthase (iNOS). We speculate that nitric oxide may be an important mediator in accommodation.

Animals↗
PubMed1998

Erosive oesophagitis: outcome of repeated long term maintenance treatment with low dose omeprazole 10 mg or placebo.

AIMS: To investigate the efficacy of daily maintenance treatment with omeprazole 10 mg in reducing the relapse rate of healed erosive oesophagitis. METHODS: Three hundred patients with erosive oesophagitis (grade 2 or greater) received omeprazole 20 mg daily for 12 weeks, followed by 40 mg daily for a further 12 weeks if required. After healing, patients were randomised to double blind treatment with omeprazole 10 mg daily or placebo for up to 18 months. On relapse the treatment cycle was repeated. RESULTS: The cumulative healing rate at 12 weeks in the initial healing period was 95%, and 96% and 98% on rehealing courses after relapse in the first and second maintenance periods respectively. After 12 weeks of treatment, 98% of patients were free from heartburn and 97% were free of all reflux related symptoms. Relapse in the subgroup of patients who relapsed in both maintenance periods was infrequent on omeprazole 20 mg daily: only 9% at two years. Gastrin concentrations rose above normal in one third of patients. One patient had linear hyperplasia of endocrine cells and another had micronodular hyperplasia. There were no side effects definitely attributable to omeprazole. CONCLUSION: Maintenance treatment with omeprazole 10 mg daily keeps about 60% of patients with erosive oesophagitis in prolonged remission. Patients relapsing once are likely to do so again; they can subsequently be treated effectively with omeprazole 20 mg daily.

Anti-Ulcer Agents↗
PubMed1998

Immunization and challenge with toluene diisocyanate decrease tachykinin and calcitonin gene-related peptide immunoreactivity in guinea pig central airways.

Toluene diisocyanate (TDI) is a potent sensitizer that causes occupational asthma in a significant proportion of subjects exposed. We used an animal model to investigate whether neuropeptide changes occur in the airways of immunized and TDI-challenged guinea pigs. Animals were immunized by weekly intradermal injections, challenged with TDI (5 to 20 ppb) after the third injection, and killed 6 h after exposure. Control guinea pigs received injections of saline. Lung tissue was processed immediately and analyzed for nerves using the streptavidin-biotin complex peroxidase method with antisera to the neural marker protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene- related peptide (CGRP). We also quantified the inflammatory infiltrate in the submucosa of central airways, and we measured the serum level of specific IgG and IgG1. Specific antibodies against TDI were present only in immunized animals. Immunized as compared with nonimmunized animals had a significant increase in eosinophils in the submucosa of central airways, and a further increase was observed 6 h after TDI challenge. Immunization and TDI challenge did not modify the number of mononuclear cells in the submucosa of central airways in both nonimmunized and immunized animals. TDI exposure did not change the overall innervation in both nonimmunized and immunized animals, but the density of PGP 9.5-positive nerves was significantly different between nonimmunized and immunized TDI-challenged animals. The density of SP-, and CGRP-immunostained nerves was significantly lower in immunized TDI-challenged than in nonimmunized animals. TDI exposure significantly decreased the density of SP-positive nerves in nonimmunized animals. A negative relationship was found between the presence of airway inflammation, as indexed by eosinophil cell infiltration, and the density of PGP 9.5-, SP-, and CGRP-immunostained nerves. In conclusion, TDI produces airway inflammation and neuropeptides changes in the central airways of immunized guinea pigs 6 h after TDI challenge. These findings support an interaction between tachykinins, inflammatory (i.e., eosinophils) and possibly immune cells.

Animals↗
PubMed1998

Functional role of rRNAs in plant translation system tested with antisense strategy.

There are regions in rRNA which are evolutionary conserved and exposed on ribosomal surface. We selected in plant material (Lupinus luteus) two of them: the alpha-sarcin domain of 26S rRNA (L-rRNA) and C loop of 5S rRNA, to be further investigated using antisense oligomers as research tools. We found inhibition of the model polypeptide biosynthesis (up to 80%) due to specific hybridization of oligomers addressed to alpha-sarcin domain and loop C. Based on our results we present the evidence for the key role played by these regions of rRNAs during protein biosynthesis in plant system. According to our hypothesis, conformational changes of these two regions are synchronised and cooperative during transition of pre- to post-translocation state of the ribosome. The correlation of structure and activity of rRNA domains in translation is shown.

Base Sequence↗
PubMed1997

The Kluver-Bucy syndrome.

Evolution of psychological disorders following head injury including memory and other cognitive disorders are common. The best known are psychiatric disturbances of various kinds after lesions of the frontal lobes. Cognitive, behavioural and emotional disorders are not usually seen in patients with bilateral temporal lesions. In our Department of Neurotraumatology we have observed 4 patients with posttraumatic lesions localized bitemporally. They developed Kluver-Bucy syndrome-rarity in human pathology-combined with three or more of the following symptoms and signs: increased oral activity, hypersexuality, hypermetamorphosis, memory disorders, placidity, loss of people recognition, bulimia. Several symptoms responded dramatically to carbamazepine. We conclude that it may be a useful agent in the treatment of this unusual syndrome.

Adult↗
PubMed1997

Pituitary neuromedin B content in experimental fasting and diabetes mellitus and correlation with thyrotropin secretion.

Fasting and diabetes mellitus in the rat model have been associated with abnormalities of thyrotropin (TSH) secretion. Neuromedin B is a bombesin-like peptide highly concentrated in the pituitary gland that has been shown to have inhibitory action on TSH secretion, acting as an autocrine/paracrine factor. Here, we aimed to determine if the pituitary content of neuromedin B would change in fasted rats (1, 2, 3, and 4 days of food deprivation) and streptozotocin (55 mg/kg body weight)-diabetic rats. The total pituitary content of neuromedin B was decreased in fasted rats, except at 2 days of fasting, as was the total protein content in the gland; however, the concentration of the peptide (femtomoles per milligram protein) did not significantly change until the fourth day of food deprivation, when an abrupt decrease in total protein happened and therefore neuromedin B concentration increased. In rats after 20 days of diabetes induction, pituitary neuromedin B increased. Serum thyroxine (T4) and triiodothyronine (T3) decreased in both disorders, whereas serum TSH was normal or decreased in 4-day fasted rats. Therefore, the caloric deprivation of diabetes and fasting changed the pituitary neuromedin B content and concentration, by mechanisms that remain to be elucidated. Since neuromedin B has been shown to act as a local inhibitor of TSH release, the results raise the possibility that increased neuromedin B concentration might be involved in the altered TSH secretion of diabetes mellitus and fasting.

Animals↗
PubMed1997

Advanced glycation end products in human penis: elevation in diabetic tissue, site of deposition, and possible effect through iNOS or eNOS.

OBJECTIVES: We hypothesized that advanced glycation end product (AGE) formation contributes to erectile dysfunction (ED) by quenching nitric oxide. Our first goal was to identify the specific AGE pentosidine in the diabetic human penis. Because AGE-mediated effects may involve inducible nitric oxide synthase (iNOS), we performed immunohistochemical and Western blot analysis of diabetic and nondiabetic human penile tissue for iNOS. Finally, because AGEs may act intracellularly to affect proteins, we set out to identify endothelial NOS (eNOS) in the human penis as an initial step in examining a possible intracellular interaction between eNOS and AGEs. METHODS: We performed high-performance liquid chromatographic analysis of diabetic human penile corpus cavernosum and serum for pentosidine and performed immunohistochemical, electron microscopic (EM), and Western blot analysis of the diabetic and nondiabetic penile corpus cavernosum and tunica for pyrraline, iNOS, and eNOS (and neural NOS [nNOS] for comparative purposes) via standard methods. RESULTS: We found a significant elevation of pentosidine in the penile tissue but not the serum of diabetic patients (average age 55.6 +/- 2.3 years) compared with that of nondiabetic patients (average age 61.8 +/- 3.6 years). Pentosidine was 117.06 +/- 9.19 pmol/mg collagen in the diabetic tunica versus 77.58 +/- 5.5 pmol/mg collagen in the nondiabetic tunica (P < 0.01) and 74.58 +/- 8.49 pmol/mg collagen in the diabetic corpus cavernosum versus 46.59 +/- 2.53 pmol/mg collagen in the nondiabetic corpus cavernosum (P < 0.01), suggesting a tissue-specific effect of the AGEs. We localized the site of deposition of the specific AGE pyrraline to the human penile tunica and the penile corpus cavernosum collagen. Immunohistochemical and EM analysis localized eNOS and iNOS to the cavernosal endothelium and smooth muscle. Western blot analysis in 6 patients revealed the following: iNOS, but no eNOS, in penile tissue from 1 insulin-dependent diabetic man; eNOS only in 1 man after radical prostatectomy; both eNOS and iNOS in 2 men with Peyronie's disease, as well as in 2 other men with impotence and hypertension. Finally, the specific iNOS inhibitor PNU-19451A significantly augmented relaxation of precontracted human cavernosal tissue, from 64.7% +/- 5.58 to 80.03% +/- 4.55 at 10 microM acetylcholine and 65.06% +/- 2.84 to 86.16% +/- 3.96 at 0.1 mM acetylcholine (n = 4, P < 0.002 and P < 0.02, respectively). CONCLUSIONS: AGEs are elevated in diabetic human penile tissue, but not in serum, and are localized to the collagen of the penile tunica and corpus cavernosum. We identified eNOS and iNOS in the human penile cavernosal smooth muscle and endothelium. The augmentation of cavernosal relaxation with a specific iNOS inhibitor, combined with the identification of iNOS protein, but not eNOS, in a patient with severe diabetes and ED, allows for speculation of a pathophysiologic mechanism for AGE-mediated ED via upregulation of iNOS and downregulation of eNOS. These data provide further insight into the mechanisms of advanced glycation end product-mediated ED and provide a foundation for further study.

Adult↗
PubMed1997

The role of nitric oxide in experimental murine sepsis due to pyrogenic exotoxin A-producing Streptococcus pyogenes.

Nitric oxide (NO) produced by inducible NO synthase (iNOS) mediates hypotension in endotoxemia. In this study, NO induction by a toxin-producing Streptococcus pyogenes isolate, H250, and by recombinant streptococcal pyrogenic exotoxin A (rSPEA) has been examined, both in vitro and in vivo. Streptococcal supernatants, but not rSPEA, induce production of nitrite by murine macrophages when both are coincubated with gamma interferon. Intraperitoneal injection of rSPEA did not cause significant production of NO. However, an elevated level of nitrate in serum was detected in a model of streptococcal fasciitis due to live H250. iNOS was localized to Kupffer cells, hepatocytes, and renal tubular cells by immunostaining. Administration of a NOS inhibitor, N(G)-monomethyl-L-arginine (L-NMMA), reduced peak concentrations of nitrate in serum but did not affect survival. NO is induced by H250, both in vitro and in vivo, mainly via SPEA-independent mechanisms. In this model, iNOS is expressed predominantly in the liver. Furthermore, in this model L-NMMA is not protective.

Animals↗
PubMed1997

Effects of ozone on epithelium and sensory nerves in the bronchial mucosa of healthy humans.

Neuropeptides released from sensory nerves during inflammation have potent effects on bronchomotor tone, airway secretion, and inflammatory cells. We investigated the effects of ozone on sensory nerves by exposing 12 healthy, nonsmoking subjects to 0.2 ppm ozone and filtered air (FA) for 2 h on separate occasions, with intermittent exercise and rest. Spirometry was performed at baseline and 15 min after exposures, and bronchoscopy (bronchial biopsy and bronchoalveolar lavage [BAL]) was done 6 h after exposure. Frozen sections were immunostained for the anatomic neural marker protein gene peptide (PGP) 9.5 and the sensory neutropeptides substance P (SP) and calcitonin-gene-related peptide (CGRP). Nerves in the submucosa were quantified by image analysis. A trend toward an increase in the levels of polymorphonuclear leukocytes (PMNs) (air versus ozone, median [interquartile range]: 3.5 [2 to 5.3%] versus 9.8 [4.2 to 16.3%], p = 0.07) and ciliated epithelial cells (median [interquartile range]: 1.6 [1.3 to 3.4%] versus 5 [2.2 to 9.8%], p = 0.05) was observed in the BAL fluid (BALF). There was a significant decrease in SP immunoreactivity following ozone exposure (median [interquartile range]: 0.6 [0.05 to 1.2] versus 0.15 [0.08 to 0.18], p < 0.05). A significant inverse correlation was observed between SP immunoreactivity and: (1) percent PMNs and ciliated epithelial cells in the BALF; and (2) percent change in FEV1 following exposure to ozone. These findings indicate that short-term exposure to 0.2 ppm ozone causes epithelial shedding and stimulates subepithelial sensory nerves to release SP into the airways. The release of SP could contribute to bronchoconstriction and subsequent neutrophil infiltration into the airways.

Adult↗
PubMed1997

The Kluver-Bucy syndrome.

Evolution of psychological disorders following head injury including memory disorders and other cognitive ones are common. The best known are psychiatric disturbances of various kind after lesions of frontal lobes. Cognitive, behavioural and emotional disorders are not usually seen in patients with bilateral temporal lesions. In our Department of Neurotraumatology we observed 4 patients with post-traumatic lesions localized bitemporally. They developed Kluver-Bucy syndrome--rarity in human pathology--with combination of three or more the following syndromes: increased oral activity, hypersexuality, hypermetamorphosis, memory disorders, placidity, loss of people recognition, bulimia. Several symptoms responded dramatically to carbamazepine. We conclude that it may be a useful agent in treatment of this unusual syndrome.

Adult↗