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Biomedical subjects

J Kowalski

Publications and source records attributed to J Kowalski.

At least 55 records · Page 3Linked to original sources
PubMed2000

In-vitro immunomodulatory effects of haloperidol and perazine in schizophrenia.

There are some reports describing concurrent changes in lymphocytic and monocytic activities in schizophrenia. In this study we investigated T cell activity in schizophrenic patients by measuring the release of interleukin-2 (IL-2) and soluble interleukin-2 receptor (sIL-2R) by T cells and the percentages of CD4+ and CD8+ cells in blood. The release of IL-2 and sIL-2R by T cells was evaluated in dilute whole blood after in-vitro stimulation with phytohemagglutinin. IL-2 levels and the percentage of CD4-cells tended to decrease and sIL-2R levels decreased significantly in schizophrenic patients. Haloperidol and perazine significantly decreased IL-2 levels and increased sIL-2R levels and the percentage CD4-cells. IL-2 and sIL-2R levels were lower in patients with a predominance of positive symptoms. The neuroleptic-induced increase in sIL-2R levels was higher in patients with a predominance of positive symptoms compared with those in whom both positive and negative symptoms were severe. The study has shown that T-cell activity is reduced in schizophrenia and that neuroleptics may have immunomodulatory properties.

Adjuvants, Immunologic↗
PubMed2000

Respiratory responses to chemical stimulation in patients with obstructive sleep apnoea.

Chemical control of breathing in obstructive sleep apnoea (OSA) patients has been studied by many authors. The results of previous studies, especially those dealing with hypoxic drive, are discordant. Respiratory responses were studied during hypercapnic and hypoxic stimulation in a group of 37 normocapnic patients with OSA during wakefulness. The diagnosis of OSA was established by standard polysomnography. These patients had increased apnoea/hypopnoea index (AHI; 51 +/- 22 (mean +/- SD)), obesity (body mass index (BMI) 32.4 +/- 5.6 kg.m-2) and normal lung function tests. The control group consisted of 14 healthy obese subjects (BMI 31.2 +/- 3.3 kg.m-2). Respiratory responses (ventilatory and mouth occlusion pressure (P0.1)) during hypercapnic and hypoxic rebreathing tests were measured with the use of computerized equipment. Respiratory responses during hypercapnic stimulation were similar to those in the control group (change in (delta) minute ventilation (V'E)/delta carbon dioxide tension (PCO2) 23.5 +/- 14.8 versus 22.3 +/- 10.0 L.min-1.kPa-1, delta P0.1/delta PCO2 4.6 +/- 3.6 versus 4.2 +/- 2.6 cmH2O.kPa-1). During isocapnic hypoxic stimulation in OSA patients the mean ventilatory response was higher than in the control group (delta V'E/delta arterial oxygen saturation (Sa,O2) 2.6 +/- 1.7 versus 1.7 +/- 0.7 L.min-1.%-1) but this difference was not statistically significant. Nevertheless, it was found that 13 (35%) OSA patients had increased ventilatory responses. The mean P0.1 response in OSA patients was higher but did not differ significantly from those in the control group (delta P0.1/delta Sa,O2) 0.43 +/- 0.38 versus 0.35 +/- 0.12 cmH2O.%-1). The results demonstrated that respiratory responses to chemical stimulation in awake normocapnic patients with obstructive sleep apnoea were in the normal range, similar to those in control obese subjects. During hypoxic stimulation some of them had increased ventilatory (35%) and mouth occlusion pressure (16%) responses.

Adult↗
PubMed2000

[Respiratory response to inspiratory resistive load changes in patients with obstructive sleep apnea syndrome].

Patients with OSA have many episodes of increased airway resistance because of repeated collapses of upper airways during night. The aim of this work was to evaluate respiratory response during chemical stimulation without and with added inspiratory resistive load (10 cmH2O/L/sec). The studies were performed during quiet breathing with air and during hypercapnic and hypoxic rebreathing tests without and with inspiratory resistive loading in 23 obese (BMI = 34.4 +/- 4.3 kg/m2) patients with OSA and in 10 healthy subjects with similar weight (BMI = 32.4 +/- 4.3 kg/m2). The measurements of respiratory responses (ventilation, mouth occlusion pressure) were performed with the use of computerized equipment. During quiet breathing in response to added load an increase of P0.1 in controls and in OSA patients was observed. During hypercapnic stimulation the ventilatory response with additional load decreased in patients as well as in controls. The slope of mouth occlusion pressure response increased significantly in controls (from 4.40 to 6.83 cmH2O/kPa, p < 0.001) and slightly weaker in OSA patients (from 4.21 to 5.43 cmH2O/kPa, p < 0.05). Although the difference between the slopes was not significant, we found that the absolute increase of P0.1 measured at point 8 kPa of PEtCO2 during loaded breathing was significantly smaller in OSA patients in comparison to controls. (2.1 vs. 10.3 cm H2O; p < 0.001). During hypoxic stimulation occlusion pressure responses were similar in both examined groups. In conclusion we postulate that OSA patients have impaired respiratory compensation of additional inspiratory load, what was demonstrated during hypercapnic rebreathing test.

Adult↗
PubMed2000

[Effect of trimetazidine on biological activity of neutrophils in patients with transient myocardial ischemia induced by exercise testing].

We estimated the effect of trimetazidine on biological activity of neutrophils in patients with exercise test--induced transient myocardial ischaemia. The study group comprised 16 patients (10 men and 6 women) aged 40-56 years (mean 48.2 years) with stable angina. Exercise test was performed on cycloer-gometer (Medicor, Hungary). Trimetazidine in a dose 3 x 20 mg/day was applied 24 hours prior to the exercise test. The control group consisted of 14 patients (9 men and 5 women) aged 37-59 years (mean 47.9 years), with stable angina, in whom exercise test was performed but the drug was not administered. Blood samples for examination were taken from basilic vein before the exercise test and 10 min afterwards. To evaluate the ability of neutrophils to aggregate the leukergy test of Fleck modified by Berliner and Aronson was applied. Oxidative metabolism of nonstimulated and stimulated by fMLP and PMA was measured using chemiluminescence method. It was shown that in patients with stable angina trimetazidine caused decrease in neutrophil aggregation. The drug did not inhibit neutrophil biological activity af-ter exercise test--induced myocardial ischaemia.

Adult↗
PubMed2000

[Comparison of HLA class I and DR class II antigen frequency in Polish patients, in relation to different stages of the disease].

The aim of this study was to analyze the association between HLA class I and class II DR frequency in the different stages of sarcoidosis in Polish population. 88 patients and 30 healthy controls have been typed. Patients were divided into three groups depending on radiological findings. In the first group were 28 cases presenting the regression of the disease. In the second were 33 patients in stable stage II or III and in the third group 27 patients with pulmonary fibrosis (stage IV). The typing was performed by NIH method using commercial sera. There were no statistically significant differences between studied group in HLA-A class I. The frequency of HLA B-18 was statistically more frequent in patients with sarcoidosis compared to healthy controls. HLA-DR1 was not present in third group of patients and the difference was significant compared to healthy controls.

Adult↗
PubMed1999

Bayesian analysis of prevalence with covariates using simulation-based techniques: applications to HIV screening.

Ignoring the limited precision of medical diagnostic tests can incur serious bias in prevalence estimation. Conversely, treating the values of sensitivity and specificity as constants, as in most studies, inevitably underestimates the variability of prevalence estimates. Bayesian inference provides a natural framework with which to integrate the variability in the estimates of sensitivity and specificity with estimation of prevalence. However, the resulting model becomes quite complicated and presents a computational challenge. Recently, Mendoza-Blanco et al. proposed a missing-data approach with simulation-based techniques to deal with the computational difficulties. Although their approach is quite effective in reducing the computational complexity into manageable tasks, their developed methodology is not general enough for modelling the effects of covariates in prevalence estimation. In this paper, we extend their work in this direction by combining their missing-data approach with a latent variable technique for modelling discrete data. The present work also generalizes the methods of Albert and Chib for Bayesian analysis of binary response data with errors in the response. We illustrate the methodology with several real data examples extracted from the literature.

AIDS Serodiagnosis↗
PubMed1999

Peroxisome proliferator-activated receptor gamma ligands are potent inhibitors of angiogenesis in vitro and in vivo.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor that functions as a transcription factor to mediate ligand-dependent transcriptional regulation. Activation of PPARgamma by the naturally occurring ligand, 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), or members of a new class of oral antidiabetic agents, e.g. BRL49653 and ciglitizone, has been linked to adipocyte differentiation, regulation of glucose homeostasis, inhibition of macrophage and monocyte activation, and inhibition of tumor cell proliferation. Here we report that human umbilical vein endothelial cells (HUVEC) express PPARgamma mRNA and protein. Activation of PPARgamma by the specific ligands 15d-PGJ2, BRL49653, or ciglitizone, dose dependently suppresses HUVEC differentiation into tube-like structures in three-dimensional collagen gels. In contrast, specific PPARalpha and -beta ligands do not affect tube formation although mRNA for these receptors are expressed in HUVEC. PPARgamma ligands also inhibit the proliferative response of HUVEC to exogenous growth factors. Treatment of HUVEC with 15d-PGJ2 also reduced mRNA levels of vascular endothelial cell growth factor receptors 1 (Flt-1) and 2 (Flk/KDR) and urokinase plasminogen activator and increased plasminogen activator inhibitor-1 (PAI-1) mRNA. Finally, administration of 15d-PGJ2 inhibited vascular endothelial cell growth factor-induced angiogenesis in the rat cornea. These observations demonstrate that PPARgamma ligands are potent inhibitors of angiogenesis in vitro and in vivo, and suggest that PPARgamma may be an important molecular target for the development of small-molecule inhibitors of angiogenesis.

Animals↗
PubMed1999

Pretreatment REM sleep and subjective sleep quality distinguish depressed psychotherapy remitters and nonremitters.

BACKGROUND: We compared pretreatment subjective and electroencephalographic sleep measures among depressed patients who remitted with psychotherapy alone and those who did not remit. METHODS: Patients were 111 midlife women with recurrent major depressive disorder. Baseline psychiatric ratings and sleep studies were conducted prior to treatment with weekly interpersonal psychotherapy. Remission was defined as a score of < or = 7 for 3 consecutive weeks on the Hamilton Depression Rating Scale. Clinical and sleep measures were compared between remitters (n = 62) and nonremitters (n = 49) using t tests and random regression. Linear discriminant function analyses were used to categorize remitters and nonremitters on the basis of sleep measures. RESULTS: Treatment nonremitters had significantly worse subjective sleep quality and significantly elevated phasic REM sleep as measured by multivariate and univariate analyses. The linear accumulation of REM activity during sleep occurred at a significantly higher rate in nonremitters than in remitters. Linear discriminant function analyses based on subjective sleep quality and REM activity correctly identified 68.3% of nonremitters and 68.5% of remitters. CONCLUSIONS: These findings highlight the role of subjective and REM sleep measures as correlates of short-term psychotherapy treatment response in major depressive disorder. Disturbed sleep may be a physiological indicator of increased limbic and brain stem arousal.

Adult↗
PubMed1999

VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation.

Hypertrophic chondrocytes in the epiphyseal growth plate express the angiogenic protein vascular endothelial growth factor (VEGF). To determine the role of VEGF in endochondral bone formation, we inactivated this factor through the systemic administration of a soluble receptor chimeric protein (Flt-(1-3)-IgG) to 24-day-old mice. Blood vessel invasion was almost completely suppressed, concomitant with impaired trabecular bone formation and expansion of hypertrophic chondrocyte zone. Recruitment and/or differentiation of chondroclasts, which express gelatinase B/matrix metalloproteinase-9, and resorption of terminal chondrocytes decreased. Although proliferation, differentiation and maturation of chondrocytes were apparently normal, resorption was inhibited. Cessation of the anti-VEGF treatment was followed by capillary invasion, restoration of bone growth, resorption of the hypertrophic cartilage and normalization of the growth plate architecture. These findings indicate that VEGF-mediated capillary invasion is an essential signal that regulates growth plate morphogenesis and triggers cartilage remodeling. Thus, VEGF is an essential coordinator of chondrocyte death, chondroclast function, extracellular matrix remodeling, angiogenesis and bone formation in the growth plate.

Animals↗
PubMed1999

Slope analysis of Auditory Brainstem Responses in children at risk of central auditory processing disorders.

The method of slope vectors was used to quantify Auditory Brainstem Responses (ABR) obtained from nine normal children and nine children at risk for central auditory processing disorders (CAPD) with language impairment, for monaural and binaural stimulation conditions. Slopes thus obtained were subjected to K-Means Cluster Analysis. Distinction between the two groups was obtained only for binaural stimulation conditions, wherein all normal children were grouped under cluster 1 with higher slope values and 6 out of 9 CAPD children were grouped under cluster 2 with lower slopes. The results suggest that there may be several subcategories among children who are found to be at risk for CAPD. One of the subcategories may comprise children who exhibit poor ABR morphology, especially during binaural stimulation conditions, which could be due to binaural interference.

Adolescent↗
PubMed1999

Pentoxifylline decreases neutrophil respiratory bursts in patients with stable angina.

We estimated the effect of pentoxifylline (PTX) on the respiratory burst (examined by chemiluminescence method) of unprimed and primed neutrophils with tumor necrosis factor-alpha (TNF-alpha) in patients with stable angina pectoris. Chemiluminescence of non-stimulated as well as formyl-methionyl-leucyl-phenylalanine (fMLP) and phorbol myristate acetate (PMA) stimulated neutrophils was measured. We studied 45 patients with stable angina subjected to percutaneous transluminal coronary angioplasty (PTCA) procedure, who were randomly divided into two groups. The study group consisted of 24 patients who were administered pentoxifylline orally, and the control group consisted of 21 patients without pentoxifylline administration. Blood samples for examination were collected from the coronary sinus and peripheral vein just before the PTCA procedure. Pentoxifylline decreased the respiratory burst of non-stimulated and fMLP-stimulated neutrophils without affecting the chemiluminescence of PMA stimulated neutrophils. Moreover, pentoxifylline diminished the chemiluminescence non-stimulated and stimulated by fMLP but not by PMA of TNF-alpha primed neutrophils. We presume that administration of PTX in stable angina patients may have a beneficial effect.

Adult↗
PubMed1999

The effects of ordered-series-of-motifs anchoring and sub-class modeling on the generation of HMMs representing highly divergent protein sequences.

Hidden Markov Models (HMMs) provide a flexible method for representing protein sequence data. Highly divergent data require a more complex approach to HMM generation than previously demonstrated. We describe a strategy of motif anchoring and sub-class modeling that aids in the construction of more informative HMMs as determined by a new algorithm called a stability measure.

Algorithms↗
PubMed1999

VEGF is required for growth and survival in neonatal mice.

We employed two independent approaches to inactivate the angiogenic protein VEGF in newborn mice: inducible, Cre-loxP- mediated gene targeting, or administration of mFlt(1-3)-IgG, a soluble VEGF receptor chimeric protein. Partial inhibition of VEGF achieved by inducible gene targeting resulted in increased mortality, stunted body growth and impaired organ development, most notably of the liver. Administration of mFlt(1-3)-IgG, which achieves a higher degree of VEGF inhibition, resulted in nearly complete growth arrest and lethality. Ultrastructural analysis documented alterations in endothelial and other cell types. Histological and biochemical changes consistent with liver and renal failure were observed. Endothelial cells isolated from the liver of mFlt(1-3)-IgG-treated neonates demonstrated an increased apoptotic index, indicating that VEGF is required not only for proliferation but also for survival of endothelial cells. However, such treatment resulted in less significant alterations as the animal matured, and the dependence on VEGF was eventually lost some time after the fourth postnatal week. Administration of mFlt(1-3)-IgG to juvenile mice failed to induce apoptosis in liver endothelial cells. Thus, VEGF is essential for growth and survival in early postnatal life. However, in the fully developed animal, VEGF is likely to be involved primarily in active angiogenesis processes such as corpus luteum development.

Age Factors↗
PubMed1998

Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation.

Vascular endothelial growth factor (VEGF) has been found to have various functions on endothelial cells, the most prominent of which is the induction of proliferation and differentiation. In this report we demonstrate that VEGF or a mutant, selectively binding to the Flk-1/KDR receptor, displayed high levels of survival activity, whereas Flt-1-specific ligands failed to promote survival of serum-starved primary human endothelial cells. This activity was blocked by the phosphatidylinositol 3'-kinase (PI3-kinase)-specific inhibitors wortmannin and LY294002. Endothelial cells cultured in the presence of VEGF and the Flk-1/KDR-selective VEGF mutant induced phosphorylation of the serine-threonine kinase Akt in a PI3-kinase-dependent manner. Akt activation was not detected in response to stimulation with placenta growth factor or an Flt-1-selective VEGF mutant. Furthermore, a constitutively active Akt was sufficient to promote survival of serum-starved endothelial cells in transient transfection experiments. In contrast, overexpression of a dominant-negative form of Akt blocked the survival effect of VEGF. These findings identify the Flk-1/KDR receptor and the PI3-kinase/Akt signal transduction pathway as crucial elements in the processes leading to endothelial cell survival induced by VEGF. Inhibition of apoptosis may represent a major aspect of the regulatory activity of VEGF on the vascular endothelium.

Amino Acid Chloromethyl Ketones↗
PubMed1998

Immunologic action of [Met5]enkephalin fragments.

The aim of this study was to evaluate the effects of [Met5]enkephalin, des-Met-[Met5]enkephalin, des-Tyr-[Met5]enkephalin, and Tyr-Gly-Gly on natural killer cytotoxic activity and on concanavalin A- and lipopolysaccharide-stimulated proliferation of B and T cells in mice. Single i.p. injections of [Met5]enkephalin, des-Met-[Met5]enkephalin, and Tyr-Gly-Gly increased both natural killer cytotoxicity and proliferation of mitogen-stimulated B and T cells. These effects were inhibited by naloxone pretreatment, which suggests the opioid mechanism of the peptides studied. The rate of lymphocytic proliferation increases not only after single injection of [Met5]enkephalin or its metabolites, but also after 3 or 7 days of treatment. Apart from the functional effects, [Met5]enkephalin, des-Met-[Met5]enkephalin, and Tyr-Gly-Gly increased the percentages of natural killer cells and T cells. The results of this study suggest that the immunomodulatory action of [Met5]enkephalin may be mediated or enhanced by its N-terminal metabolites des-Met-[Met5]enkephalin and Tyr-Gly-Gly.

Adjuvants, Immunologic↗
PubMed1998

Augmenting effect of opioids on nitrite production by stimulated murine macrophages.

The effects of methionine-enkephalin and the selective agonists of mu-, delta- and kappa-opioid receptor subtypes [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin, [D-Pen(2,5)]enkephalin U-50488 on the production of nitrite by activated peritoneal murine macrophages were studied. Macrophages were activated with interferon-gamma plus lipopolysaccharide in the presence or absence of graded concentrations of opioids. Methionine-enkephalin and mu-; delta- and kappa-agonists combined with interferon-gamma plus lipopolysaccharide caused an increase in nitrite release from cultured macrophages. Only 10 mM U-50488 led to a decrease in nitrite release from interferon-gamma and LPS-stimulated macrophages. This effect was not produced in a naloxone-sensitive manner. The opioids added to the fresh culture 8 h after the stimulation of macrophages by interferon-gamma plus lipopolysaccharide--when an inducible form of nitric oxide synthase activity is presumably expressed--did not alter the rate of nitrite production. This suggests that the effect of opioids on nitric oxide synthase is produced at the transcriptional level. The opioid receptor antagonist naloxone reduced the stimulatory effect of opioids on nitrite production by stimulated macrophages. Opioids added to the culture of resting macrophages did not change nitrite release from macrophages which were later induced with interferon-gamma plus lipopolysaccharide. The results of this study suggest that methionine-enkephalin can modulate the immune response by controlling, via opioid receptors, the production of nitric oxide.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗