PubMed Health⌕ Search

Biomedical subjects

J Greger

Publications and source records attributed to J Greger.

At least 19 recordsLinked to original sources

The effect of interleukin-6 on hepatitis B virus replication in peripheral blood mononuclear cells in vitro.

Although the major target organ for hepatitis B virus (HBV) is the liver, the possibility of infection of peripheral blood mononuclear cells (PBMCs) with HBV has also been reported. This study was performed to analyze the course of HBV infection of PBMCs and to investigate the influence of interleukin-6 (IL-6) on the efficiency of infection of PBMCs with HBV in vitro. PBMCs isolated from a healthy donor were infected by exposing to a HBsAg-, HBeAg-positive serum in the presence or absence of exogenous IL-6. The efficiency of infection was estimated by HBV DNA determination in the cells and medium in the course of infection. The results of this study show that the presence of IL-6 during the PBMCs infection with HBV increased the efficiency of this infection.

Cells, Cultured↗

Activity of type IV collagenases (MMP-2 and MMP-9) in primary pulmonary carcinomas: a quantitative analysis.

PURPOSE: Matrix metalloproteinases MMP-2 and MMP-9 are implicated in invasion and metastasis of malignant tumors. We investigated the expression and activation of MMP-2 and MMP-9 in lung cancer compared with normal lung parenchyma, and looked for a potential marker of malignancy. METHODS: Thirty-six pulmonary carcinomas and paired normal lung specimens were analyzed by gelatin zymography and computer-assisted image analysis for the expression of MMP-2 and MMP-9. RESULTS: We showed that expression of both type IV collagenases was remarkably higher in carcinoma samples than in lung parenchyma. The MMP-9 levels in lung cancer were over twofold higher than in normal lung tissues. The levels of latent and active forms of MMP-2 in lung cancer samples were, correspondingly, 3.8- and 17-fold higher than in lung parenchyma. The tumor/normal (T/N) ratios of MMP-2 were negatively correlated with the hemoglobin levels and erythrocytes number. CONCLUSIONS: A high level of the active form of MMP-2 in almost all of the carcinomas and the near lack of its activation in normal lung parenchyma shows that MMP-2 activation is associated with the malignant phenotype and may serve as a good marker of malignancy. The correlation between low hemoglobin level and T/N ratio of MMP-2 may indicate significance of MMP-2 for angiogenesis.

Aged↗

Continuous femoral blocks improve recovery and outcome of patients undergoing total knee arthroplasty.

This study was designed to determine the effects of continuous femoral infusion (CFI) on total knee arthroplasty recovery. A total of 92 patients were distributed in 3 groups: Patients in group 1 received general anesthesia followed by patient-controlled analgesia (PCA) with morphine (n = 33), patients in group 2 received 3-in-1 and sciatic blocks followed by CFI (n = 29), and patients in group 3 received epidural analgesia (n = 30). Blocks reduced postoperative morphine requirement by 74% (vs group 1; P<.05) and 35% (vs group 3; P<.05). Blocks provided better recovery than PCA with morphine or an epidural. The use of CFI was associated with a reduction of postoperative bleeding by 72% (vs group 1; P<.05) and allowed better performance on continuous passive motion. CFI was associated with a 90% decrease in serious complications and a 20% decrease in the length of hospitalization. CFI represents a better alternative than PCA or epidural analgesia for postoperative pain management and immediate rehabilitation after total knee arthroplasty.

Adult↗

Differentiated reactivity of whole blood neonatal platelets to various agonists.

Neonatal platelets have been occasionally reported to show a reduced response to various agonists. The molecular mechanism(s) of such a depressed reactivity remains unclear. To further address this problem we studied neonatal platelet activation with thrombin, TRAP (thrombin receptor activating peptide, Ser-Phe-Leu-Leu-Arg-Asn-Pro-Asn-Asp-Lys-Tyr-Glu-Pro-Phe) and ADP in 42 healthy 1-2 day old neonates using a whole peripheral blood flow cytometry. The neonates did not show an increased fraction of P-selectin-positive circulating platelets, whereas the expression of GPIb (glycoprotein Ib) in resting neonatal platelets was significantly lower compared to adults. Neonatal platelets were significantly less reactive than adult platelets to thrombin and TRAP, especially at lower agonist concentrations, but not to ADP or when incubated for 1 h at room temperature. Activation of neonatal platelets with agonists resulted in a marked alterations in the expression of P-selectin, whereas the internalization of GPIb was not affected. The reduced neonatal platelet sensitivity to thrombin and TRAP was accompanied by significantly reduced ATIII (antithrombin III) and increased prothrombin fragment F(1+2) in neonatal plasma. We conclude that various receptor systems potentially able to bind thrombin are relatively insensitive in neonatal platelets. The novelty of our work is that neonatal platelet hyposensitivity is not a generalized phenomenon, but concerns only selected agonists and selected receptor systems.

Adenosine Diphosphate↗

Reduction of operating and recovery room times and overnight hospital stays with interscalene blocks as sole anesthetic technique for rotator cuff surgery.

BACKGROUND: The effort to decrease hospital stays and to increase operating room efficacy has become an important consideration in the practice of anesthesia. METHODS: Fifty-three patients who underwent shoulder rotator cuff repair in the sitting position were divided into four groups according to the anesthesia technique used: Group 1 (general anesthesia), Group 2 (interscalene block), Group 3 (interscalene combined with general anesthesia) and Group 4 (general anesthesia combined with local injection of local anesthetics). Interscalene blocks were performed preoperatively, using a nerve stimulator. After appropriately locating the brachial plexus, a mixture of 40 ml of 2% lidocaine and 0.5% bupivacaine (v/v) was injected. RESULTS: As compared to general anesthesia, the use of an interscalene block alone reduced the following operating room times: 1) from the patient's arrival in the operating room to the beginning of surgery and 2) from the end of surgery to the patient's departure from the operating room. Use of the interscalene block also resulted in a reduction of recovery time when compared to Groups 1, 3 and 4 by 40, 56 and 66%, respectively. Compared to Group 1, this anesthesia technique was furthermore associated with a 64% decrease in the number of patients hospitalized overnight. CONCLUSIONS: This study confirms that the interscalene block as sole anesthesia technique is safe and effective and can contribute to shorten the hospital length of stay of patients undergoing shoulder rotator cuff surgery.

Adult↗

Regional anesthesia for outpatient orthopedic surgery.

The constant search for increased efficiency and reduction of hospital length of stay has led to an increase number of major orthopedic procedures performed as outpatients and the increase in the associated intensity and duration of acute postoperative pain. Although, it is well established that single peripheral blocks provide adequate anesthesia and excellent immediate postoperative analgesia in patients undergoing minor ambulatory orthopedic surgery, the postoperative acute pain benefit is limited to less than 24 hours. However, many patients required over 24 hours of intensive postoperative analgesia. Furthermore the need for immediate postoperative physical therapy in orthopedics dictates that local anesthetics be chosen on the basis of their safety and ability to produce preferential sensory blocks. As early as 1946, Ansbro proposed the use of continuous nerve blocks to prolong the duration of analgesia of nerve block technique during anesthesia. Continuous nerve blocks have also been used for the acute postoperative pain control of patients undergoing major orthopedic surgery as in-patients. This technique has been proven to be safe and effective in controlling acute postoperative pain and improve functional outcome. The recent introduction of safer local anesthetics producing preferential sensory blocks along with the development of ambulatory pumps has allow to extend the use of these continuous block techniques to ambulatory patients. Recent development also included the use of cox2 inhibitors along with cold maximize postoperative analgesia. This multimodal approach has been proven to be safe and efficacious as much for resting pain than pain associated with exercise.

Ambulatory Surgical Procedures↗

Further studies on cytostatic activity of alkoxymethyl purine and pyrimidine acyclonucleosides.

The influence of 14 acyclonucleosides, derivatives of adenine, guanine, uracil and thymine on the phosphorylation of dAdo, dGuo, dCyd and dThd occurring in the cytosol of growing amelanotic melanoma transplanted to Syrian hamsters, as well as on inhibition of tumor growth were studied. From among the studied ACNs eight were tested earlier (Modrzejewska et al., 1996, The influence of alkoxymethyl purine and pyrimidine acyclonucleosides on growth inhibition of Kirkman-Robbins hepatoma and possible mechanism of their cytostatic activity, Z. Naturforch. 51c, 75-80); from among the newly synthesized ACNs, 1,3-N,N-diallyloxymethylthymine (AMT2), 1-N-allyloxymethyl-5,6-tetramethyleneuracil (AMUTM), and tested previously 1-N-allyloxymethylthymine (AMT1), administered i.p. in a dose of 0.2 mmol/kg body weight reduce the tumor mass from 0.98 g to 0.64 g +/- 0.11 g (i.e. 35% +/- 12%). 48 hours after i.p. administration of the mentioned ACNs in the same dose a reduction of tumor mass is accompanied by the inhibition of dAMP, dGMP and dTMP synthesis. AMT1 inhibits dThd phosphorylation from 6.2 to 4.22; AMT2 suppresses dAdo, dGuo and dThd phosphorylation by, correspondingly, from 2.8 to 1.7, from 10.8 to 7.5 and from 6.2 to 4.2; AMUTM depresses dAMP synthesis from 2.8 to 1.6 (all data: mumol of 2'dNMP formed per mg of protein per min. x 10(-4)). None of the 14 studied acyclonucleosides influences dCMP synthesis. In vivo, after hydration of allyloxymethyl group to hydroxypropoxymethyl residue (having -CH2OH group), AMT1, AMT2 and AMUTM undergo phosphorylation to corresponding triphosphates. Phosphorylated ACNs are not incorporated into tumor DNA, however they inhibit dAdo, dGuo and dThd incorporation into DNA. It is concluded that ACN triphosphates are not substrates for DNA polymerase but, competing with dATP dGTP and dTTP, inhibit incorporation of these 2'dNTP into DNA and, in consequence, reduce tumor growth, which is presumed to be the main mechanism of cytostatic activity of the studied ACNs.

Animals↗

The activity of thymidine phosphorylase correlates with tumor size and lymph nodes status in breast carcinoma.

The platelet-derived endothelial cell growth factor (PD-ECGF) is one of the potent angiogenic factors. Recently, its homology with thymidine phosphorylase (dThdPase), an enzyme involved in pyrimidine nucleoside metabolism, has been shown. In the present study, dThdPase activity was evaluated spectrophotometrically in 43 breast carcinomas and in 19 cases of non-neoplastic breast tissues. The mean dThdPase activity in breast cancer was almost six fold higher than in normal, non-neoplastic breast tissues (1.92 and 0.29 mumol thymine (T) x mg prot.-1 x h-1 respectively). The enzyme activity significantly correlated with axillary lymph node status (p = 0.0076) and with tumor size (p = 0.0099). Besides, the intratumoral microvessel density (MD) was evaluated using the CD 31 mouse anti-human monoclonal antibody, and there was no correlation between the level of enzymatic activity and a number of microvessels. The positive significant correlation of thymidine phosphorylase activity with prognostic factors in breast cancer patients with no relation to the number of microvessels needs further examination to confirm the prognostic significance of the level of dThdPase.

Analysis of Variance↗

Thymidine kinase activity in homogenates of rat thyroid lobes from euthyroid, hypothyroid and/or hyperthyroid rats incubated with EGF: studies ex vivo in vitro.

OBJECTIVE: To examine thymidine kinase (TK - ATP: thymidine 5'-phosphotransferase, EC 2.7.1.21) activity in homogenates of rat thyroid lobes incubated in vitro with epidermal growth factor (EGF). METHODS: The thyroid lobes were collected from euthyroid, hypothyroid and/or hyperthyroid animals. Hypothyroidism was developed in the experimental rats by an administration of 0.1 % solution of propylthiouracil (PTU) in drinking water for 2 weeks, while hyperthyroidism was obtained by daily i.p. injections of L-thyroxine (50 microg/kg, B.W.), also for 2 weeks. After collecting, the thyroids were incubated for 4 hours in RPMI 1640 medium with an addition of 20 mM of Hepes buffer, 15% FCS, penicillin (200 U/ml), streptomycin (10 ug/ml) and with EGF (Sigma) (0.1 ng/ml, 10 ng/ml, 1000 ng/ml). The control lobes were incubated without any addition of EGF to the medium. TK activity was expressed as the amount of reaction products, measured by ascending chromatography. RESULTS: 1. in the absence of EGF, TK activity in the homogenates of thyroid lobes from hypothyroid rats was lower, while it was higher in the lobes from hyperthyroid animals, when compared to these obtained from euthyroid controls; 2. EGF in the concentration of 0.1 ng/ml or 1000 ng/ml decreased, while that in the concentration of 10 ng/ml increased TK activity in lobes collected from euthyroid or hyperthyroid rats; 3. in the tissue collected from hypothyroid rats, the addition of EGF (0.1 ng/ml or 10 ng/ml) caused a slight increase in TK activity versus hypothyroid controls - a tendency towards diminishing TK activity could be observed as parallel to increasing EGF concentration. CONCLUSIONS: TK activity in the homogenates of rat thyroid lobes depends on the functional thyroid status and on applied EGF concentration in vitro.

Analysis of Variance↗

Thymidine Kinase (EC 2.7.1.21) Activity in Homogenates of Human Thyroid Tissue, Following the Exposure to Epidermal Growth Factor (EGF) in vitro.

The activity of thymidine kinase (TK - EC 2.7.1.21) was measured in human thyroid tissue homogenates incubated in vitro. This enzyme functions as a part of the pyrimidine salvage pathway involved in DNA synthesis. The thyroid tissue was obtained from the thyroids of patients thyroidectomized at the Department of Endocrine Surgery, Medical University of lodz because of: 1. non-toxic nodular goiter (NTNG): tissue macroscopically unchanged, woman 46 yrs; 2. non-toxic adenoma (NTA), woman 37 yrs; 3. toxic adenoma (TA), woman 45 yrs. The tissue was incubated for 4 hours in RPMI 1640 medium (Gibco), containing Hepes buffer, 15 % FCS and the examined substance - epidermal growth factor (EGF) - used in five different concentrations (0.1 ng/ml, 1 ng/ml, 10 ng/ml, 100 ng/ml, 1000 ng/ml). The TK activity was measured according to Cheng and Prusoff (1974) as modified by Greger and Draminski (1989). The reaction products were separated by ascending chromatography. It was found that: 1. TK activity in thyroid tissue from NTNG and NTA did not significantly differ from control incubations without EGF, while it was significantly higher in the thyroid tissue from TA; 2. in the range of concentrations from 1 ng/ml to 1000 ng/ml, EGF increased TK activity in the macroscopically unchanged tissue from NTNG; 3. the incubation of the tissue from NTA with EGF resulted in the increase of TK activity in a concentration-dependent manner; 4. EGF stimulated TK activity in the tissue from TA, but the difference was significant only after the lowest EGF concentration. The obtained results suggest a possible role of EGF in the pathogenesis of NTNG, as well as of NTA and TA in humans.

Journal Article↗

Molecular insights into the anticoagulant-induced spontaneous activation of platelets in whole blood-various anticoagulants are not equal.

The spontaneous anticoagulant-dependent platelet activation in vitro may potentially interfere with the determination of haemostatic parameters. The effects of various blood anticoagulants on platelet activation were monitored using flow cytometry. Regardless of a blood anticoagulant used (EDTAK2, heparin, citrate or PPACK), platelet activation began immediately after blood withdrawal and was most pronounced in the EDTAK2-anticoagulated blood samples. The progressing expression of GMP-140 antigen was accompanied by the enhanced abundance of the subunit beta 3 of the platelet membrane integrin alpha IIb beta 3 without parallel changes in the fluorescence attributed to the complex form of the integrin alpha IIb beta 3. The increased expression of GMP-140 was paralleled by the enhanced platelet clumping in the samples anticoagulated with either EDTAK2 or heparin, and the raised platelet microparticles in blood withdrawn into citrate. The EDTAK2-induced platelet activation was markedly reduced by methyl 2,5-dihydroxycinnamate, tyrosine kinase inhibitor. The influence of disodium EDTA on platelet membrane dynamics closely mimicked the alterations induced upon the interaction of fibrinogen with platelet GPIIb-IIIa. Thus, the EDTAK2-induced platelet activation might result from an interference with platelet membrane protein structure and conformation and possibly related to an "unspecific" trigerring of a signal transduction pathway. Overall, EDTAK2 and heparin appeared the least suitable anticoagulants, particularly with the regard to the expression of GMP-140 antigen. The failure to recognize the importance of a spontaneous anticoagulant-induced platelet activation may result in misdiagnoses during the monitoring of coagulation parameters.

Amino Acid Chloromethyl Ketones↗

Effect of substance P and its precursor alpha-protachykinin on intracellular free calcium concentration in human polymorphonuclear leukocytes.

The increase in intracellular free calcium concentration is an important step in signal transduction leading to phagocyte activation. The undecapeptide substance P can influence various functions of human polymorphonuclear leukocytes, including chemotaxis, phagocytosis, and respiratory burst. In this study we investigated the ability of low-concentration (that can occur in vivo) substance P (10(-7) M) and its precursor alpha-protachykinin (3 x 10(-7) M) to increase the intracellular free calcium concentration in human polymorphonuclear leukocytes. Cells isolated from ten healthy donors were incubated with substance P or alpha-protachykinin in 1 mM calcium medium for 5 min and the intracellular free calcium concentration was monitored using the fluorescent calcium indicator Fura-2am. Polymorphonuclear leukocytes from 40% of donors responded to both agonists. The substance P- and alpha-protachykinin-induced increase in intracellular free calcium concentration was 59 +/- 13 nM and 58 +/- 12 nM and the extracellular calcium influx contributed to 87 +/- 8% and 54 +/- 8% of the calcium response, respectively. alpha-Protachykinin released almost all the calcium from intracellular stores, while substance P mobilized only 24 +/- 5% of this calcium pool. Finally, cells that responded to a single challenge with substance P and alpha-protachykinin were able to increase their intracellular free calcium concentration in response to each of three consecutive stimulations with these agonists. This may be an additional mechanism by which substance P and its precursor modify the function of human polymorphonuclear leukocytes.

Calcium↗

[Non-compliance and lack of indications for depot treatment as reasons for exclusion from adequate prevention of recurrence].

OBJECTIVE: The paper reports on the recruitment of a multicenter study on ambulant prophylactic treatment of schizophrenic disorders. METHODS: For a study of the relapse-preventative effect of different dose patterns of Flupentixol, a screening phase was carried out among of 1129 schizophrenic patients. The aim of the screening phase was to establish the criteria for exclusion or inclusion in the treatment phase of the study. RESULTS: Only 62 patients could be included. The reason for 54 patients not being included was a lack of compliance from either the patient or the clinician. The meaning of patient- and therapist-compliance in carrying out a multicenter study is also discussed.

Double-Blind Method↗

The activity of thymidine kinase in homogenates of rat thyroid lobes incubated in vitro in the presence of vasoactive intestinal polypeptide; interactions with atropine and carbachol.

We examined the effect of vasoactive intestinal polypeptide (VIP) on thymidine kinase (TK) activity in the tissue of rat thyroid lobes incubated in vitro. Additionally, thyrotropin, epidermal growth factor, as well as atropine and carbachol were studied. It was shown that: 1. thyrotropin and epidermal growth factor did not essentially affect TK activity; 2. the effect of VIP was dose dependent: the high concentrations of peptide (10(-7) M and 10(-5) M) suppressed, while the lower concentrations (10(-15)M, 10(-13)M, 10(-11)M and 10(-9) M)-enhanced TK activity; 3. atropine tended to increase TK activity, however, that rise did not attain statistical significance; 4. VIP, when used together with atropine, decreased TK activity when compared with the activity in question after exposure to atropine alone; 5. carbachol suppressed TK activity; 6. the joint action of carbachol and VIP did not significantly change the activity of the examined enzyme.

Animals↗