Biomedical subjects

J Jakus

Publications and source records attributed to J Jakus.

At least 19 recordsLinked to original sources

PubMed2006

Free radicals, lipid peroxidation and the antioxidant system in the blood of cows and newborn calves around calving.

The oxidative stress of birth in cattle (Bos taurus) was evaluated by measuring steady state concentration of free radicals in whole blood, rate of lipid peroxidation and activity of antioxidant enzymes in erythrocytes, antioxidant capacity of blood plasma in 14 calves at birth and four times after birth until 3 weeks of age and also in their mothers at calving. The same parameters were also measured in 58 dairy cows before calving, at parturition and after calving. Free radical concentration in the blood of newborn calves was higher than in cows confirming that birth means oxidative stress for calves. Red blood cell malondialdehyde in calves was the highest at birth and following the first solid feed intake at the third week. Superoxide dismutase activity increased in calves during the first three weeks of life. Ferric reducing ability of plasma was higher in calves at birth than in cows and decreased thereafter. Higher superoxide dismutase activity in red blood cells and lower ferric reducing ability of plasma in dairy cows was found at calving compared to the average of all pre- and post-calving results. We conclude that the blood of newborn calves is well prepared to deal with the oxidative stress of birth, and that such a stress is present even when some fingerprint markers of redox imbalance show no apparent alterations. Stress of calving has minor effects on the antioxidant system of cows.

Animals↗

PubMed2005

Increased cell-cell adhesion, a novel effect of R-(-)-deprenyl.

The neuroprotective effect of the antiparkinsonian monoamine oxidase (MAO)-B inhibitor, R-(-)-deprenyl has been under investigation for years. Cytoskeleton, a main component of cell adhesion, is involved in the development of R-(-)-deprenyl-responsive diseases, the effect of the drug on cell adhesion, however, is not known. We examined the effect of R-(-)-deprenyl on cell-cell adhesion of neuronal and non-neuronal cells. R-(-)-deprenyl treatment resulted in a cell type- and concentration-dependent increase in cell-cell adhesion of PC12 and NIH3T3 cells at concentrations lower than those required for MAO-B inhibition, while S-(+)-deprenyl was not effective. This acitvity of R-(-)-deprenyl was not prevented by the cytochrome P-450 inhibitor, SKF525A, while deprenyl-N-oxide, a newly described metabolite, also induced an increase in cell-cell adhesion. The effect of R-(-)-deprenyl was not reversible during a 24-hour recovery period. In summary, we described a new, MAO-B independent effect of R-(-)-deprenyl on cell-cell adhesion which can contribute to its neuroprotective function.

Animals↗

PubMed2005

Cough and laryngeal muscle discharges in brainstem lesioned anaesthetized cats.

Experiments were carried out to determine whether there are separate drives from the selected neuronal networks of the brainstem affecting the discharge patterns of laryngeal and respiratory pump muscles during cough. Twenty-four non-decerebrate spontaneously breathing cats anesthetized with sodium pentobarbitone were used. Microinjections of kainic acid into the lateral tegmental field of the medulla, medullary midline or pontine respiratory group eliminated the cough evoked by mechanical stimulation of the tracheobronchial and laryngopharyngeal mucosa. These stimuli, in most cases, provoked irregular bursts of discharges in the posterior cricoarytenoid and thyroarytenoid laryngeal muscles (or they had no effect on them). No pattern of laryngeal muscle activities following lesions resembled the laryngeal cough response. Lesions of the target regions did not result in any apparent changes in the eupnoeic pattern of laryngeal activity. Neurons of the medullary lateral tegmental field, raphe nuclei and the pontine respiratory group seem to be indispensable for the configuration of the central cough motor pattern. However, these neurons do not appear to be essential for the discharge patterns of laryngeal motoneurons during eupnoea. The residual laryngeal "cough" responses are probably mediated by an additional motor drive.

Anesthesia↗

PubMed2004

Cough, expiration and aspiration reflexes following kainic acid lesions to the pontine respiratory group in anesthetized cats.

The importance of neurons in the pontine respiratory group for the generation of cough, expiration, and aspiration reflexes was studied on non-decerebrate spontaneously breathing cats under pentobarbitone anesthesia. The dysfunction of neurons in the pontine respiratory group produced by bilateral microinjection of kainic acid (neurotoxin) regularly abolished the cough reflexes evoked by mechanical stimulation of both the tracheobronchial and the laryngopharyngeal mucous membranes and the expiration reflex mechanically induced from the glottis. The aspiration reflex elicited by similar stimulation of the nasopharyngeal region persisted in 73% of tests, however, with a reduced intensity compared to the pre-lesion conditions. The pontine respiratory group seems to be an important source of the facilitatory inputs to the brainstem circuitries that mediate cough, expiration, and aspiration reflexes. Our results indicate the significant role of pons in the multilevel organization of brainstem networks in central integration of the aforementioned reflexes.

Abdominal Muscles↗

PubMed2004

Brainstem areas involved in the aspiration reflex: c-Fos study in anesthetized cats.

Expression of the immediate-early gene c-fos, a marker of neuronal activation was employed in adult anesthetized non-decerebrate cats, in order to localize the brainstem neuronal populations functionally related to sniff-like (gasp-like) aspiration reflex (AR). Tissues were immunoprocessed using an antibody raised against amino acids of Fos and the avidin-biotin peroxidase complex method. The level of Fos-like immunoreactivity (FLI) was identified and counted in particular brainstem sections under light microscopy using PC software evaluations in control, unstimulated cats and in cats where the AR was elicited by repeated mechanical stimulation of the nasopharyngeal region. Fourteen brainstem regions with FLI labeling, including thirty-seven nuclei were compared for the number of labeled cells. Compared to the control, a significantly enhanced FLI was determined bilaterally in animals with the AR, at various medullary levels. The areas included the nuclei of the solitary tract (especially the dorsal, interstitial and ventrolateral subnuclei), the ventromedial part of the parvocellular tegmental field (FTL -- lateral nuclei of reticular formation), the lateral reticular nucleus, the ambigual and para-ambigual regions, and the retrofacial nucleus. FLI was also observed in the gigantocellular tegmental field (FTG -- medial nuclei of reticular formation), the spinal trigeminal nucleus, in the medullar raphe nuclei (ncl. raphealis magnus and parvus), and in the medial and lateral vestibular nuclei. Within the pons, a significant FLI was observed bilaterally in the parabrachial nucleus (especially in its lateral subnucleus), the Kolliker-Fuse nucleus, the nucleus coeruleus, within the medial region of brachium conjunctivum, in the ventrolateral part of the pontine FTG and the FTL. Within the mesencephalon a significantly enhanced FLI was found at the central tegmental field (area ventralis tegmenti Tsai), bilaterally. Positive FLI found in columns extending from the caudal medulla oblongata, through the pons up to the mid-mesencephalon suggests that the aspiration reflex is thus co-ordinated by a long loop of medullary-pontine-mesencephalic control circuit rather than by a unique "center".

Anesthesia↗

PubMed2003

Activity of the laryngeal abductor and adductor muscles during cough, expiration and aspiration reflexes in cats.

We studied the temporal relationships and the patterns of electromyographic activities of the posterior cricoarytenoid and thyreoarytenoid muscles (laryngeal abductor and adductor), the diaphragm and abdominal muscles in anesthetized cats during mechanically induced tracheobronchial and laryngopharyngeal coughs, expiration and aspiration reflexes. The posterior cricoarytenoid muscle activity reached the maxima just before the peak of diaphragmatic activity in both types of cough and aspiration reflexes and slightly before the top of abdominal muscle activity in coughs and the expiration reflex. Thus, this muscle contributes to the inspiratory phase of coughs and aspiration reflex and also to the expulsive phase of coughs and the expiration reflex. The thyreoarytenoid muscle presented strong discharges in the compressive phase of coughs and expiration reflex (during the rising part of the abdominal muscle activity) and in the subsequent laryngoconstriction (following the diaphragmal and/or abdominal muscle activity) in all four reflexes. This muscle was also slightly activated at the beginning of the aspiration reflex. The existence of four phases of the cough reflex is also discussed.

Abdominal Muscles↗

PubMed2002

Prediction of tumoricidal activity and accumulation of photosensitizers in photodynamic therapy using multiple linear regression and artificial neural networks.

The biological activities of a congeneric series of pyropheophorbides used as sensitizers in photodynamic therapy have been predicted on the basis of their molecular structures, using multiple linear regression and artificial neural network (ANN) computations. Theoretical descriptors (a total of 81) were calculated by the 3DNET program based on the three-dimensional structure (3D) of the geometry-optimized molecules. These input descriptors were tested as independent variables and used for model building. Systematic descriptor selections yielded models with one, two or three descriptors with good cross-validation results. The predictive abilities of the best fitting models were checked by shuffling and cross-validation procedures. ANN was suitable for building models for both linear and nonlinear relationships. Lipophilicity was sufficient to predict the accumulation of the sensitizers in the target tissue. Weighted holistic invariant molecular descriptors weighted by atomic mass, Van der Waals volume or electronegativity were also needed to predict photodynamic activity properly. Our models were able to predict the biological activities of 13 pyropheophorbide derivatives solely on the basis of their 3D molecular structures. Moreover, linear and nonlinear variable selection methods were compared in models built linearly and nonlinearly. It is expedient to use the same method (linear or nonlinear) for variable selection as for parameter estimation.

Antineoplastic Agents↗

PubMed2002

[Regulation of respiration and its sleep-related disorders].

Four basic control mechanisms of breathing (brainstem respiratory centre, peripheral and central chemoreceptors, intero- and exteroceptive reflexes and suprapontine influences), as well as their sleep-related disorders are analysed. A decrease in central chemoreceptor sensitivity to CO2 and an increase in upper airway resistance during sleep result in hypoventilation and mild hypoxaemia already in physiological conditions. Compensatory increase in ventilatory effort with synchronous inhibition of pharyngeal dilators during sleep reduces the upper airway lumen manifesting with snoring, upper airway resistance syndrome, and OSA. The resulting hypoxaemia may cause marked cardiovascular, neuro-psychic, endocrine-metabolic and behavioural disorders. The augmented ventilatory effort and hypoxaemia evoke reflex dilation of airways and arousal from sleep, stimulating the sympatho-adrenal system, which provokes autoresuscitation by gasping preventing fatal asphyxia. Failure of this autoresuscitation mechanism seems to cause SIDS. Elimination of voluntary breathing by sleep either in Ondine's curse induced by lesions of respiratory centre, or in congenital central hypoventilation syndrome caused by insufficient central chemoreceptors result in respiratory failure and death. Nocturnal attacks of bronchial and cardiac asthma, lung oedema and other consequences of pulmonary congestion are also discussed. The pathomechanism of extreme daytime sleepiness, chronic fatigue, and disorders of memory, cognitive and other brain functions, are also analysed. Severe cardiovascular consequences of SAS may manifest acutely as angina pectoris, myocardial infarction. dysrhythmias, transient ischaemic attacks and even stroke or sudden cardiac death. OSAS may result also in development of hypertension, central obesity, diabetes mellitus, erectile dysfunction, depression, and various behavioural disorders.

Humans↗

PubMed2000

The expiration reflex from the vocal folds.

The authors present their 30 years' experience with expiration reflex. The reflex can be elicited from vocal folds by mechanical, chemical or electrical stimulation of the superior laryngeal nerve of man and laboratory animals, except mice and rats. It manifests itself by a short, forcible expiratory effort without a preceding inspiration which is indispensable for cough effort. The role of expiration reflex is to prevent penetration of foreign bodies into airways, expelling phlegm and detritus from subglottal area. The initial inspiration before expiration is undesired and could lead to inspiration pneumonia. The reflex is well known to laryngologists as '"laryngeal cough." Its receptors are small in number, localised mainly in medial margin of vocal folds deep in mucosa which can explain their stability in pathological conditions of the larygx. Afferentiation of the reflex is via laryngeal nerve similarly to sneezing and cough. Expiration reflex is not co-ordinated by a single "centre" but rather by a network system in the brain stem. Its motor pattern is supposedly produced by "multifunctional" population of medullar neurones in Botzinger complex and the rostral ventral respiratory group involved also in the genesis of breathing and cough. However, in cats also other neurones may play a vital role in production, shaping and mediation of the motor pattern of respiratory reflex, localised in rostral pons, lateral tegmental field or in the raphe medullar midline.

Animals↗

PubMed2000

Kainic acid lesions to the lateral tegmental field of medulla: effects on cough, expiration and aspiration reflexes in anesthetized cats.

We have tested the hypothesis that neurons of both the ventral reticular nucleus and the adjacent parts of the lateral tegmental field (LTF) may be important for the production of motor programs associated with cough, expiration and aspiration reflexes. Our studies were conducted on non-decerebrate, spontaneously breathing cats under pentobarbitone anesthesia. Dysfunction of the medullary LTF region above the obex, produced by uni- or bilateral injections of kainic acid (a neurotoxin), regularly abolished the cough reflex evoked by mechanical stimulation of both the tracheobronchial and laryngeal regions and in most cases also the expiration reflex induced from the glottal area. However, some electrical activity still occurred in the neurogram of the recurrent laryngeal nerve during probing the laryngeal and glottal regions. Interestingly, the aspiration reflex elicited from the nasopharynx regularly persisted, although with lower intensity after the LTF lesion. Nevertheless, successive midcollicular decerebration performed in four cats also abolished the aspiration reflex. These experiments demonstrate the importance of medullary LTF neurons for the normal occurrence of cough and expiration reflexes. One possible explanation for the elimination of these expulsive processes is that the blockade of the LTF neurons may remove an important source of a facilitatory input to the brainstem circuitries that mediate cough and expiration reflexes. In addition, the potential importance of the mesencephalic reticular formation for the occurrence of the aspiration reflex and the role of the LTF in modulating both the eupnoeic breathing and the blood pressure are also discussed.

Anesthesia↗

PubMed2000

Contribution of upper airway reflexes to apnoea reversal, arousal, and resuscitation.

Cardiorespiratory decompensation or even death may result from dysfunction of upper airway reflexes during sleep. This could manifest, for example, as a lack of pharyngeal dilation in obstructive sleep apnoea or failure of autoresuscitation by gasping in sudden infant death syndrome. Data obtained from experiments in anaesthetized cats suggest several clinicophysiological applications for upper airway reflexes possessing important pathogenetic and therapeutic potentials. Such reflex effects include: 1. Pharyngeal dilation as additional treatment in obstructive sleep apnoea. 2. Bronchodilation after deep nasal breathing in asthmatic attacks. 3. Oesophageal sphincter relaxation alleviating gastro-oesophageal reflux. 4. Provocation of sniff- and gasp-like aspiration for reversal of central apnoea. 5. Arousal from sleep increasing the general reactivity. 6. Increase in muscle tone underlying behavioural defence reactions. 7. Increase in sympathetic activity contributing to powerful cardiopulmonary-cerebral resuscitation. 8. Adrenergic reaction mediated by catecholamine secretion.

Arousal↗

PubMed2000

[Experience with polysomnography in the diagnosis of sleep apnea].

Whole-night recording of 9-30 parameters and calculation of various indices allow differentiation of various sleep related breathing disorders and estimation of their severity (Fig. 1, 2). Parallel monitoring of changes in ventilation, arterial oxygen saturation, ECG, EEG, EMG and others, give a possibility to appreciate the gradual development of cardiovascular, neuropsychic, endocrine-metabolic and other consequences of sleep related breathing disorders, their dependence on different phases and stages of sleep as well as their alterations by treatment.

Humans↗

PubMed1999

Physico-chemical modeling of the role of free radicals in photodynamic therapy. IV. Quantitative aspects of photodynamic effects on free radicals generated in cell cultures.

Production and the mechanism of the interactions of free radicals generated by stimulated macrophages in the presence of luminol and a free radical inhibitor was investigated to determine the possibility of using luminol-dependent chemiluminescence for studying photodynamic effects in biology. Earlier measurements have been revisited and additional experiments performed indicating that oxidation products of luminol neither inhibit the in vitro formation of radicals nor quench CL. Simulation based on the mechanism suggested revealed that the likely value for the rate constant of the primary step between luminol and superoxide anion radicals producing luminol radicals is 5x10(2)-1x10(3) M-1s-1. It has been established that the ratio of the concentration of radicals generated by the biological system to that formed by oxidation of luminol exceeds 10(3); that is, the contribution of the latter is negligible and the system is appropriate to measure quantitatively the effect of excited photosensitizers on free radicals.

Animals↗

PubMed1998

p21(WAF1/Cip1) retards the growth of human squamous cell carcinomas in vivo.

The excessive proliferation exhibited by cancer cells is frequently a result of their failure to adequately regulate cell cycle progression. In the present study, we developed a xenograft model of oral cancer in athymic mice, using squamous carcinoma cell lines and examined the ability of the cyclin-dependent kinase inhibitor p21 (WAF1/Cip1) to retard tumour growth in vivo, using a retroviral delivery system. Human p21 cDNA was cloned by polymerase chain reaction, expressed, and the encoded protein shown to have biological activity in in vitro kinase assays. Amphotropic retrovirus cultures which expressed recombinant p21 were generated and used to treat established squamous cell carcinoma xenografts. Two weeks following onset of treatment tumours injected with p21 virus producer cells showed a reduction in size between 3- and 10-fold compared with tumours which received control cells which produced control virus alone. The data indicate that recombinant p21 may be of future use for therapeutic intervention in oral cancer.

Animals↗

PubMed1998

Effects of medullary midline lesions on cough and other airway reflexes in anaesthetized cats.

The involvement of rapheal and medial parts of the medullary reticular formation in both generation of airway reflexes and changes in breathing were studied in 18 chloralose or pentobarbitone anaesthetized, non-paralyzed cats. Chemical lesions to the medullary midline region (0-4 mm rostral to the obex) produced by localized injections of the neurotoxin kainic acid regularly abolished the cough reflexes evoked from the tracheobronchial and laryngopharyngeal regions and in most cases also the expiration reflex induced from the glottal area. The aspiration reflex elicited from the nasopharynx was spared, but was less intense. However, the signs of cough and expiration reflexes were preserved in the neurogram of the recurrent laryngeal nerve. The experiments have shown the importance of raphe nuclei and other medullary midline structures for the occurrence of cough and expiration reflexes. One possible explanation for the elimination of these expulsive processes is the removal of an important source of facilitatory input to the spinal respiratory motoneurons or to the brainstem circuitries that mediate cough and expiration reflexes. The role of the medullary midline in modulation of eupnoeic breathing and blood pressure is also discussed.

Anesthetics, Intravenous↗

PubMed1997

Altered expression and activity of G1/S cyclins and cyclin-dependent kinases characterize squamous cell carcinomas of the head and neck.

Progressive deregulation of the cell-division cycle is thought to contribute to the establishment and progression of neoplasia. Previously, we have documented the in vivo inactivation of p16INK4A, an inhibitor of G1 cyclin-dependent kinases, in squamous cell carcinomas of the head and neck region. In the present study, we extend these findings by examining the expression and functional activity of cyclin-dependent kinases (CDKs) and their regulatory subunits using a model system of cell lines derived from squamous cell carcinomas. Increased activity of CDK4 and 6 was universal in tumor cells compared with normal keratinocytes, reflecting over-expression of either or both kinases. In contrast to other studies, over-expression of cyclin D1, a regulatory subunit of CDK4 and 6, was not observed. Increased activity of CDK2 was less frequent and was related to over-expression of cyclin A and/or E. All tumor cell lines showed increased expression of proliferating cell nuclear antigen compared to normal keratinocytes. Four SCC cell lines, including one tumor-metastasis pair derived from a single patient, failed to express the p15INK4B transcript. Western blot analysis of cell lysates revealed normal or reduced levels of p27KIP1 in tumor cells compared to normal keratinocytes. However, failure to express wild-type p53 was not reflected by lower levels of p21WAF1. Our data suggest that cell-cycle deregulation is likely to occur by multiple mechanisms during the genesis of head and neck squamous cell carcinomas. Furthermore, p16INK4A is likely to be the primary target for inactivation on chromosome 9p21 in these tumors as p15INK4B loss occurs less frequently.

Carcinoma, Squamous Cell↗

PubMed1997

Carboxyl-terminal domain of p27Kip1 activates CDC2.

A variant form of p27 was unexpectedly detected in a synchronized culture of NIH3T3 cells treated with serum. The expression levels of this form of p27 which lacked its amino (NH2)-terminal region reached maximum during G2/M phase. Since the appearance of the NH2-terminal truncated form of p27 coincided with increased expression of Cdc2, we hypothesized that p27 may play a role in regulating Cdc2 catalytic activity. To test this hypothesis, wild type p27, as well as the amino-terminal (Np27) and carboxyl-terminal (Cp27), were individually expressed, purified, and examined for their ability to regulate CDC2 kinase activity in vitro. Our data showed that both p27 and Np27 inhibited CDC2 kinase activity. However, in marked contrast, Cp27 enhanced the CDC2 kinase activity. In vitro kinase assays showed that Cp27 and p27 were phosphorylated by CDC2, whereas Np27 was not. In addition, we demonstrated that deletion of the putative CDC2 phosphorylation site in the carboxyl-terminal domain of Cp27 diminished activation of CDC2 kinase activity otherwise stimulated by Cp27. A similar deletion did not have any effect on the inhibitory function of p27. Together these results suggest that the carboxyl-terminal domain of p27 may activate CDC2 kinase activity in vivo during G2/M and that this effect may be regulated by serine/threonine phosphorylation.

3T3 Cells↗

PubMed1997

Functional characterization of p53 molecules expressed in human squamous cell carcinomas of the head and neck.

Mutation of the p53 tumor suppressor gene has been demonstrated in a large proportion of human head and neck squamous cell carcinomas (HNSCCs) and has been assumed to play a role in the pathogenesis of these tumors, although no formal evidence of functional aberration has been demonstrated. In this study, we isolated cDNA clones encoding the entire p53 coding region from six human HNSCC cell lines that showed aberrant patterns of p53 expression in the parental cells, analyzed their nucleotide sequences, and characterized their function in vivo. cDNAs cloned from four cell lines harbored alterations within the p53 coding sequence (one missense mutation, one missense mutation plus in-frame deletion, one splice donor mutation, and a 1-nt insertion). HN30 cells, which contained wild-type p53 nucleotide sequences, showed a high constitutive level of protein expression. HN26 cells contained wild-type coding sequences but did not express the 53-kDa protein, although the mRNA was transcribed and a molecule of increased molecular mass (70 kDa) was observed by western blotting. Functional studies revealed that none of the four proteins encoded by mutant cDNAs were able to transactivate expression of a reporter plasmid containing a wild-type p53 consensus binding site when cotransfected into p53-null cells, whereas molecules encoded by wild-type p53 cDNAs increased reporter gene expression about a hundredfold over uninduced levels. Co-expression of each mutant cDNA with wild-type p53 cDNA and a wild-type p53-responsive reporter gene demonstrated that each of the proteins encoded by mutant cDNAs harbored some degree of inhibitory activity that varied depending on the mutation present. Thus, aberrant p53 function as a result of mutation or altered expression characterizes oral squamous cell carcinomas. The inhibitory activity of these molecules may be a mechanism for deregulation of the function of co-expressed wild-type p53 that may be of importance during the early stages of tumor development.

Blotting, Western↗