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Biomedical subjects

M Jasinski

Publications and source records attributed to M Jasinski.

17 recordsLinked to original sources

Botulinum toxin treatment of spasticity in diplegic cerebral palsy: a randomized, double-blind, placebo-controlled, dose-ranging study.

This study evaluated the efficacy and safety of three doses of botulinum toxin A (BTX-A; Dysport) in 125 patients (mean age 5.2 years, SD 2; 54% male)with dynamic equinus spasticity during walking. Participants were randomized to receive Dysport (10, 20, or 30 units/kg) or placebo to the gastrocnemius muscle of both legs. Muscle length was calculated from electrogoniometric measurements and the change in the dynamic component of gastrocnemius shortening at four weeks was prospectively identified as the primary outcome measure. All treatment groups showed statistically significant decreases in dynamic component compared with placebo at 4 weeks. Mean improvement in dynamic component was most pronounced in the 20 units/kg group, being equivalent to an increase in dorsiflexion with the knee extended at 19 degrees, and was still present at 16 weeks. The safety profile of the toxin appears satisfactory.

Botulinum Toxins, Type A↗

GATA1-Cre mediates Piga gene inactivation in the erythroid/megakaryocytic lineage and leads to circulating red cells with a partial deficiency in glycosyl phosphatidylinositol-linked proteins (paroxysmal nocturnal hemoglobinuria type II cells).

Patients with paroxysmal nocturnal hemoglobinuria (PNH) have blood cells deficient in glycosyl phosphatidylinositol (GPI)-linked proteins owing to a somatic mutation in the X-linked PIGA gene. To target Piga recombination to the erythroid/megakaryocytic lineage in mice, the Cre/loxP system was used, and Cre was expressed under the transcriptional regulatory sequences of GATA-1. Breeding of GATA1-cre (G) transgenic mice with mice carrying a floxed Piga (L) allele was associated with high embryonic lethality. However, double-transgenic (GL) mice that escaped early recombination looked healthy and were observed for 16 months. Flow cytometric analysis of peripheral blood cells showed that GL mice had up to 100% of red cells deficient in GPI-linked proteins. The loss of GPI-linked proteins on the cell surface occurred late in erythroid differentiation, causing a proportion of red cells to express low residual levels of GPI-linked proteins. Red cells with residual expression of GPI-linked proteins showed an intermediate sensitivity toward complement and thus resemble PNH type II cells in patients with PNH. Recombination of the floxed Piga allele was also detected in cultured megakaryocytes, mast cells, and eosinophils, but not in neutrophils, lymphocytes, or nonhematopoietic tissues. In summary, GATA1-Cre causes high-efficiency Piga gene inactivation in a GATA-1-specific pattern. For the first time, mice were generated that have almost 100% of red cells deficient in GPI-linked proteins. These animals will be valuable to further investigate the consequences of GPI-anchor deficiency on erythroid/megakaryocytic cells.

Animals↗

Stripping analysis of nucleic acids at a heated carbon paste electrode.

A new electrically heated carbon paste electrode has been developed for performing adsorptive stripping measurements of trace nucleic acids. Such coupling of electrochemistry at electrically heated electrodes with adsorptive constant-current stripping chronopotentiometry offers distinct advantages for trace measurements of nucleic acids. The application of increased temperatures during the deposition step results in dramatic (4-34-fold, depending on temperature applied) enhancement of the stripping signal. Such improvement is attributed to the accumulation step at the heated electrode. Forced thermal convection near the electrode surface facilitates the use of quiescent solutions and hence of ultrasmall volumes. Using an electrode temperature of 32 degrees C and a quiescent solution during the 1-min accumulation, the response is linear over the 1-8 mg/L range tested, with a detection limit of 0.5 mg/L. Such electrode heating technology offers great promise for various applications involving thermal manipulations of nucleic acids.

Carbon↗

Comparison of retrograde vs simultaneous ante/retrograde cold blood cardioplegia.

BACKGROUND: To evaluate the homeostasis of myocardium during simultaneous continuous retrograde and antegrade cardioplegia vs retrograde continuous cardioplegia. METHODS: 40 patients who underwent elective operation of coronary arteries bypass grafting were randomly assigned to 2 groups: group one consisted of 24 patients who received retrograde continuous blood cardioplegia; group two consisted of 16 patients who received simultaneous continuous ante/retrograde cardioplegia. The following measurements were taken: acidosis, oxygen content, oxygen extraction and oxygen consumption; they were taken before and after cross-clamp releasing from coronary sinus effluent and from arterial line. Incidence of low cardiac output, ventricular fibrillation, raised cardiac enzymes and ischemic changes on ECG was noted. RESULTS: In simultaneous group such parameters as acidosis, oxygen content, oxygen extraction and myocardial oxygen consumption recovered after cross-clamping and changes of their values were respectively: 0.0005, 0.87 ml/100 ml, 0.098 and 1.4 ml/min. The same parameters didn't recovered in retrograde group and changes were respectively: 0.05 - p=0.2; 3.7 ml/100 ml - p=0.006, 0.29 p=0.006 and 7.4 ml/min - p=0.03. These changes were significant between groups. CONCLUSIONS: Metabolic viability of myocardium measured with oxygen utilisation is better preserved with simultaneous antegrade and retrograde cardioplegia.

Adult↗

Effect of amlodipine upon the protective activity of antiepileptic drugs against maximal electroshock-induced seizures in mice.

Amlodipine, a calcium channel antagonist of the dihydropyridine class, up to 10 mg kg(-1)(i.p.) did not significantly affect the threshold for electroconvulsions. However, this calcium channel antagonist (10 mg kg(-1)) enhanced the anticonvulsive activity of carbamazepine, valproate and phenobarbital against maximal electroshock-induced seizures in mice. Furthermore, amlodipine (5 mg kg(-1)) intensified the protection offered by carbamazepine. This effect was associated with the increased free plasma level of carbamazepine in the presence of amlodipine. Amlodipine did not influence the free or total plasma level of phenobarbital and valproate, so a pharmacokinetic interaction is not probable for valproate and phenobarbital. The anticonvulsive action and free plasma level of diphenylhydantoin was not modified by amlodipine. The combined treatment of the calcium channel antagonist and antiepileptics caused motor impairment (evaluated in the chimney test). Long-term memory (assessed in the passive avoidance test) in case of combinations of amlodipine with carbamazepine or diphenylhydantoin was not affected. The combination of amlodipine with valproate or phenobarbital significantly influenced the retention in this test. A possible usefulness of amlodipine as add-on therapy in epileptic patients may be limited by its considerable adverse effect revealed by behavioural tests. The pharmacokinetic interaction between carbamazepine and amlodipine might have some clinical importance for patients treated with these drugs.

Amlodipine↗

Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumors and do not occur in leiomyomas or leiomyosarcomas.

Gastrointestinal stromal tumors (GISTs) comprise the largest subset of mesenchymal tumors of the gastrointestinal tract. These neoplasms differ histologically and immunohistochemically from typical leiomyomas and leiomyosarcomas. Most GISTs express CD34 and CD117 (c-kit protein) but not desmin. Recently, gain-of-function mutations of c-kit proto-oncogene have been shown in five solitary GISTs and in tumors and leukocytes from a family with multiple GISTs. An in-frame deletion or a point mutation in exon 11 of c-kit was detected in these cases. Stable transfection of the mutant c-kit complementary DNA was also shown to induce malignant transformation of murine lymphoid cells, suggesting that the c-kit mutations contribute to tumor development. In this study, we evaluated 43 GISTs and 14 smooth muscle tumors for mutations in the exon 11 of c-kit by a PCR-assay. Half of the malignant GISTs (12/24) and only one benign GIST (1/19) revealed mutant bands. No mutant bands were found in 3 leiomyomas and 11 leiomyosarcomas. Sequence analysis confirmed the presence of an in-frame deletion of 3-21 bp in all 13 GISTs with mutant bands. Wild-type bands from 8 malignant and 11 benign GISTs and 7 smooth muscle tumors without mutant bands were cloned and sequenced. Additional mutations were found in 3 malignant and 2 benign GISTs. There were no mutations in 3 leiomyomas and 4 leiomyosarcomas. The mutation status of exon 11 did not correlate with immunohistochemically detectable expression of the CD117, as virtually all GISTs with or without such mutations showed CD117 immunoreactivity. The c-kit mutations occur preferentially in malignant GISTs and might be a clinically useful adjunct marker in the evaluation of GISTs. The conservation of the c-kit mutation pattern, observed in consecutive lesions from the same patients, suggests that these mutations might be useful tumor markers in monitoring recurrence or minimal residual disease.

Adult↗

Molecular pathological analysis of testicular diffuse large cell lymphomas.

The molecular pathology of 20 lymphomas, which presented as testicular masses in patients with no evidence of previous lymphoma, was analyzed. These lymphomas occurred in men with a median age of 69 years (range, 37 to 87 years). Nine of the 14 patients with follow-up died of lymphoma (median survival, 12 months). All cases were diffuse large B-cell lymphomas that were positive for CD20 and commonly showed plasmacytoid differentiation (10 of 20 cases). Three cases were Burkitt's-like large cell lymphomas. Infiltration by lymphoma in the seminiferous tubules was seen in most cases. All lymphomas were negative for human herpesvirus 8 and Epstein-Barr virus by 35 cycles of polymerase chain reaction (PCR), suggesting that these viruses are not involved in the pathogenesis of primary testicular diffuse large B-cell lymphomas (DLBCL). PCR-based studies for t(14;18) and t(11;14) translocations, commonly seen in follicular and mantle-cell lymphomas, were negative in all cases. Nucleotide sequences of the V-D- and J segments of the immunoglobulin heavy chain gene (IgH) rearrangements obtained in 12 cases after PCR amplification were analyzed and compared with known germlines. The frequency of VH-family use in testicular DLBCL was similar to that reported for normal peripheral blood lymphocytes and follicular lymphomas. This contrasts with the previously published findings of preferential use of the VH3- or VH4-family by nodal DLBCL. Comparison with the published germlines showed a low similarity index in most of the cases, suggesting the presence of extensive somatic mutations. Ongoing mutation, as indicated by intraclonal variation in IgH sequence, was observed in all sequenced cases, suggesting direct antigen stimulation, which represents another difference between primary testicular and nodal DLBCL. Our results suggest that testicular lymphomas represent a subset of DLBCL that differs from their nodal counterparts in several respects. Their histological and molecular features show some similarities to those seen in marginal zone (MALT) lymphomas.

Adult↗

Detection of the SYT-SSX fusion transcripts in formaldehyde-fixed, paraffin-embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma.

Identification of the t(X;18)(p11.2;q11.2) translocation and detection of the resulting SYT-SSX1 or SYT-SSX2 fusion transcripts are useful diagnostic markers for synovial sarcoma. In this study, we developed a polymerase chain reaction (PCR) assay to amplify SYT-SSX fusion transcripts. The primer sequences were designed to generate small PCR products and to amplify sequences of all known SSX genes as fusion partners for the SYT gene. RNA was obtained from formaldehyde-fixed and paraffin-embedded tissues of 22 immunohistochemically characterized synovial sarcomas, 6 of them cytogenetically confirmed as t(X;18) positive. The SYT-SSX fusion transcripts were detected in 21 of the 22 analyzed cases. The type of the fusion was identified by the specific restriction enzyme digestion pattern as SYT-SSX1 in 13 cases and SYT-SSX2 in 7 cases; in 1 case, the type could not be assigned. None of the cases showed involvement of the SSX3, SSX4, or SSX5 genes, the other members of the SSX gene family. In seven cases, the SYT-SSX1 or SYT-SSX2 fusion transcripts were demonstrated in frozen tissue using a different PCR assay. The PCR products were confirmed as SYT-SSX sequences by sequencing in five randomly selected cases. Fifteen other sarcomas and related tumors were negative for SYT-SSX fusion transcripts. The PCR assay used in this study performs well in formaldehyde-fixed and paraffin-embedded tissue, and it shows a high specificity. This assay can be used as an adjunct test for diagnostically difficult cases or in retrospective studies to refine the diagnosis of synovial sarcoma in archival material.

Adolescent↗

Evidence for B cell-mediated activation of V delta 1+ T lymphocytes during progression of HIV infection.

Progression of HIV-induced immunodeficiency is associated with both B cell activation and an increased proportion of Vdelta1+ T cells in PBL. To examine whether the peripheral expansion of Vdelta1+ cells is driven by activated B cells, we isolated CD19+ PBL from HIV+ individuals at different stages of infection and used them to stimulate Vdelta1+ T cell clones. The Vdelta1+ T cell clones were isolated from HIV+ individuals and selected on the basis of cytotoxic activity and IFN-gamma expression in response to lymphoblastoid cell lines (LCLs) established from patients with AIDS (AIDS-related LCLs) but not LCLs of HIV- donors. Peripheral blood B cells from HIV+ patients induced IFN-gamma expression in these Vdelta1+ clones, and their stimulatory ability was associated with up-regulated expression of the CD38 activation Ag and with a 6- to 10-fold increased spontaneous Ig production. Stimulation of CD19+ PBL from HIV+ individuals with cross-linked anti-CD40 mAb or rgpl20 further augmented induction of IFN-gamma expression in the Vdelta1+ cells. The isolated Vdelta1+ T cell clones expressed the Jdelta1 gene segment, but differed in Vgamma gene segment usage and in the junctional region of TCR-delta chains, indicating Vdelta gene-determined recognition. These results provide evidence that the peripheral expansion of Vdelta1+ cells in HIV infection is associated with phenotypic and functional alterations of B cells, due to chronic activation during progression to AIDS.

ADP-ribosyl Cyclase↗

Comparison of retrograde versus antegrade cold blood cardioplegia: randomized trial in elective coronary artery bypass patients.

OBJECTIVE: Myocardial areas distal to complete coronary artery occlusion are poorly protected by antegrade cardioplegia. Hence, retrograde cardioplegia becomes an important adjunct in myocardial protection. An aim of the study was to compare both methods prospectively. METHODS: 158 coronary artery bypass grafting (CABG) patients were randomly assigned to two groups according to myocardial protection technique: 89 patients to group 1--retrograde cold blood cardioplegia (RCBC); and 69 patients to group 2--antegrade cold blood cardioplegia (ACBC). Preoperative parameters were similar but cross-clamp time and volume of cardioplegia needed were higher in the retrograde group. The results were assessed on the basis of: (1) clinical outcome; (2) ECG and enzymatic parameters of ischemia; (3) assessment of early systolic function by means of cardiac output (CO), stroke work index (SWI), left ventricular stroke work index (LVSWI) and right ventricular stroke work index (RVSWI) taken before, and 1 and 5 h after coming off bypass; (4) late systolic and diastolic function by echo assessment of segmental contractility of 17 segments and indexes of peak transmitral flow (TMI) taken 7 days and 6 months after operation. RESULTS: Ischemic events, inotropes and ventricular fibrillation on reperfusion were significantly more frequent in the antegrade group. Sinus rhythm at an early stage postoperatively was found more frequently in the retrograde group. All these parameters became comparable 24 h after operation. Early myocardial recovery was better in the retrograde group where intraoperative improvement in CO and SWI was significant. At the same time, SWI decreased significantly in the antegrade group. RVSWI changes were similar in both groups. There were no differences in mortality and perioperative MI. Late myocardial performance by segmental contractility and diastolic transmitral flow were similar in both groups. CONCLUSIONS: Retrograde continuous blood cardioplegia reduces ischemic injury and permits better early recovery of myocardial function. There is no difference, however, regarding long-term assessment of myocardial recovery.

Blood↗

Results of mechanical prosthetic valve replacement in active valvular endocarditis.

UNLABELLED: To evaluate the results of mechanical prosthetic valve replacement for active endocarditis 71 patients were reviewed. They were treated surgically between 1988 and 1993 in our institution. Mechanical valves were used in 54 patients (group 1) and bioprosthetic valves were used in 17 patients (group 2). In terms of demographic, clinical and surgical variables prior to operation groups were statistically the same. Follow up ranged from 2-63 months averaged 21 months. This study was carried out to: asses cardiac status postoperatively and assess the rate of mortality, recurrency and reoperations. METHODS: Evaluation of cardiac status was assessed on the basis of symptoms and findings by examination, ECG, X-ray, echocardiography, and laboratory tests. Data analysis was done by means of statistical tests like: Student's "t"-test, Fisher exact test, one sided test of difference between two percentages, Kaplan Meyer survival analysis and Cox test. RESULTS: 4-year mortality was 20% in group 1 comparing to 28,6% in group 2, when early mortality were 13% in group 1 comparing to 17% in group 2. These differences were not significant. The recurrency rate was 8,5% in group 1 comparing to 28,6% in group 2 which was statistically significant (p=0.028). Especially early recurrency rates differed significantly between groups and were 4,2% in group 1 comparing to 21% in group 2 (p=0.022). The reoperations rate was 4,2% in group 1 comparing to 21% in group 2 which was statistically significant (p=0.022). Clinical status showed satisfactory values and significant improvement in both groups, slightly better after mechanical valve replacement. CONCLUSION: It is concluded that mechanical valve is recommended for valve replacement in active valvular endocarditis first of all due to low recurrency and reoperation rate.

Adult↗

Surgical treatment of atrial septal aneurysm.

The atrial septal aneurysm (ASA) is a morphologic abnormality known to cause peripheral and pulmonary embolism. 28-52% patients with ASA have embolic events. However ASA -- with no other concomittant cardiac patology has rarely been reported as the indication for open heart surgery. In this work, five cases of patients operated for ASA are presented. Embolic complications with cerebral symptoms were presented in three cases. The diagnosis of ASA was established with the use of transesophageal echocardiography. The surgical correction of the defect was performed in extracorporeal circulation. The aneurysmal part of interatrial septum was excised and replaced with a pericardial patch. The postoperative course was uneventful. The patients have no new embolic events during the follow up period of one year.

Adult↗

Interaction of HIV-1 gp120 molecule fragments with human monocytes: different requirements for tumor necrosis factor-alpha and IL-6 production.

The HIV-1 gp120 recombinant protein fragment encompassing aa residues 410-511, that contains the CD4 binding region (rp120cd), and fragment aa 446-511, which lacks the sequence responsible for CD4 binding (rp120), were synthesized to study their ability to induce TNF synthesis in human monocytes. The rp120cd stimulated TNF alpha secretion by monocytes while the rp120 and full-length recombinant protein (FL gp120), used as control, failed to do so. However, FL gp120 stimulated peripheral blood mononuclear cells (PBMC) and lymphocytes for TNF production and this was inhibited by anti-CD4 MAb. The rp120cd also caused TNF secretion by PBMC that was not blocked by this antibody. Furthermore, FL gp120 but not rp120cd inhibited anti-CD4 mAb binding to CEM cells. Hence, FL gp120 may cause TNF release from lymphocytes by binding to CD4, while rp120cd interacts with monocytes but not lymphocytes and induces TNF production by a mechanism not involving CD4 binding. Unexpectedly, FL gp120 but not rp120cd stimulated IL-6 secretion and IL-6 mRNA synthesis in monocytes. The FL gp120-induced production of IL-6 by monocytes was inhibited by anti-CD4 monoclonal antibody (MAb). Thus, there may be different requirements for TNF induction in lymphocytes and monocytes stimulated with various preparations of gp120 and for the selective induction of cytokines in monocytes. The enhanced production of TNF in HIV infection and AIDS may involve distinct cellular sources and different mechanisms.

Antibodies, Monoclonal↗

Tumour-cell-induced production of tumour necrosis factor by monocytes of gastric cancer patients receiving BCG immunotherapy.

Human peripheral blood monocytes cocultured with tumour cells were used as an in vitro model of in situ interactions between tumour-infiltrating macrophages and the tumour. Tumour cells stimulated de novo expression of the human tumour necrosis factor alpha (TNF) gene in monocytes and caused the release of TNF into the culture supernatant. A group of 14 patients with stage IVA gastric cancer receiving adjuvant chemotherapy (5-FU, Adriamycin, mitomycin C: FAM) or immunochemotherapy (BCG+FAM) was investigated for the ability of monocytes to produce TNF in vitro upon stimulation with tumour cells or purified protein derivative of tuberculin (PPD). Patients were followed at biweekly intervals, i.e. before each instillation of BCG epicutaneously over a period of 10 weeks. It was found that monocytes of some patients receiving BCG at the end of the observation period had an enhanced ability to produce TNF following stimulation with tumour cells. In contrast, such production was not substantially altered during the study period in patients on chemotherapy. PPD-induced TNF production was much weaker and was not significantly changed during this observation time. We infer that BCG immunotherapy may induce the subtle changes in some cancer patients that lead to an increased interaction between monocytes and tumour cells and result in enhanced production of cytokine(s) with antitumour properties.

BCG Vaccine↗

[Iodized polyvidone (betadine) and prevention of postoperative infection. A multicenter study].

A multicentre study of a new preparation of povidone iodine (5% betadine) was carried out on 150 patients undergoing cataract surgery. Pre-operatively the eye was prepared by daubing the peri-ocular skin and a two-minute instillation into the conjunctival fornices. No other antiseptic was applied. Tolerance to the product was evaluated in all the patients: clinical evaluation postoperatively and during a 60-day follow-up period confirmed that the preparation was harmless to the eye. Microbiological investigations (comprising conjunctival swabbing, bacterial culture and count of the bacterial species isolated, before and after application of the product) performed on 60 patients showed a significant fall in the number of colonies after treatment.

Administration, Topical↗