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K Jakab

Publications and source records attributed to K Jakab.

15 recordsLinked to original sources
PubMed1999

Analysis of CAG repeat expansion in Huntington's disease gene (IT 15) in a Hungarian population.

Huntington's disease (HD) is a neurodegenerative disorder with autosomal dominant inheritance. The genetic defect is a CAG trinucleotide repeat expansion at the 5' end of the IT 15 gene on chromosome 4. This gene has not been analyzed in the Hungarian population yet. To obtain data DNA from 26 HD patients, 18 members of their families and 70 normal controls was amplified in the involved region by polymerase chain reaction. The CAG repeat numbers varied from 37 to 70 (median: 43) in HD patients and asymptomatic carriers, while individuals of the normal control group had 10-36 CAG repeat numbers (median: 18). The length of CAG repeat expansion in Hungarian HD patients was similar to that reported from other countries. The group of normal controls had the same CAG repeat expansion as populations reported from Western European countries. It is a useful piece of data for population genetics to prove that the population of Hungary is a mélange of different nations that influenced the history of the country in the last 11 centuries. As opposed to this, the only closely related nation, the Finnish, was genetically more isolated during this time, so the frequency of HD (and also the number of CAG repeats in normal individuals) proved to be exceptionally low.

Adult↗
PubMed1999

Responses to single-dose thrombopoietin decrease with higher platelet counts in mice.

Since the description of human thrombopoietin (TPO) we investigated the thrombocytosis-inducing capacity of human serum samples derived from individuals with altered thrombocytopoiesis. Several times the degree of thrombocytosis developing in recipient mice differed markedly even when applying the same human material. In the last 2 years, we applied single doses of recombinant human TPO (rHuTPO) to random-bred CFLP mice, and the same observation was made. Taken together with previous information (before 1970) it was possible to select cases in which the percent increases in circulating platelet counts inversely correlated with the starting levels. It appears, however, that apart from the known absorbing role of platelets and megakaryocytes, the response to single doses of exogenous rHuTPO in mice depends, at least partially, on an unknown endogenous homeostatic mechanism. Mixing thrombopoietically active human sera with platelet-free normal serum in a 1:1 ratio remarkably reduced the thrombocytosis-inducing capacity. Repeated pharmacological doses of TPO, applied in the majority of the reported trials, however, easily obscure the physiological control mechanism.

Animals↗
PubMed1998

[A new radiation-free conditioning in bone marrow transplantation and dibromo-mannitol therapy in chronic myeloid leukemia].

A new, radiation-free, conditioning protocol, containing the original Hungarian mitobronitol (DBM) (DBM/ cytosine arabinoside/cyclosphosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from HLA identical sibling donors between 1990-1997. In spite of some prognostically disadvantageous factors (half of them were above 40 years, 10 out of 36 patients were in accelerated phase, the disease history was longer than 2 years in average) the overall survival (30/36) and the leukemia free survival rate (26/36) were in accordance with the best international results. Transplantation-related toxicity was remarkably reduced in comparison to bone marrow transplantation performed by total body irradiation/cyclophosphamide (TBI/Cy) or busulphan/cyclophosphamide (Bu/Cy) conditioning protocols. Acute graft versus host disease was present in lower percentage (9/36) and the number of serious cases was only 2/36. Chronic GVH disease, generally known to be associated with antileukemic effect (GVL), occurred in 25 of cases. Early haematological relapse among the 34 patients with functioning graft occurred in 6 patients which rate is slightly higher than reported after TBI/Cy or Bu/Cy conditioning treatment. There was no relapse among patients transplanted within one year post-diagnosis and patients having CML with accelerated phase. The leukemia free post-transplant period was in association with the chronic GVH disease and full chimeric state.

Adolescent↗
PubMed1998

Diagnostics of multidrug resistance in cancer.

Multidrug resistance (MDR), caused by the overexpression of two membrane proteins, MDR1-Pgp and/or MRP, is a major obstacle in the chemotherapy of cancer. The proper laboratory diagnosis of clinical multidrug resistance is still an unresolved question, and this uncertainty, in a vicious cycle, does not allow the correct evaluation of the clinical relevance of the MDR phenomenon. More-over, inefficient MDR diagnostics hinders the development of effective resistance-modulation strategies. In this review, after describing the basic features of the MDR drug pump proteins, the currently employed diagnostic methods are discussed. We suggest that a quantitative, functional method developed in our laboratory may provide a major help in the laboratory assessment of cancer MDR.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

[Survey of one hundred patients with chronic granulocytic leukemia from the view of recent developments].

Data of 100 selected CGL patients were considered. There were 50 male and 50 female patients with an average 38.1 and 41.5 years of age, respectively. Seventy nine patients were in stable, chronic and 21 patients were in accelerated phase. Patients first admitted in blastic phase were excluded. Twenty two patients were subjected to bone marrow transplantation. Characteristically low levels of neutrophil alkaline phosphatase were absent in about 10 to 25% of early cases. It was considered that the level of positive cells could eventually point to the extent of normal population. In the group of the accelerated patients the neutrophil alkaline phosphatase scores were regularly high and the serum cholesterol values lower than those among stable-phase patients. The role of G-CSF (granulocyte colony stimulating factor) was considered. Secondary myelofibrosis was frequently associated with low serum cholesterol. Average survival time was 41 month among non-transplanted and 63+ months among identically-transplanted patients. In accordance with the literature, authors point out that in the presence of any factor not permitting transplantation, prolonged high-dose interferon-therapy could be the first choice, because unlike chemotherapeutic agents used till now, it prolongs survival. Apart from this autotransplantation with marrow or with circulating blood derived stem cells should be considered.

Adolescent↗
PubMed1995

Lymphocyte subset reconstitution after allogeneic bone marrow transplantation using radiation-free conditioning regimen for patients with chronic granulocytic leukemia.

Conditioning regimens for BMT are important in determining transplant outcome. A radiation-free protocol containing Mitobronitol (DBM), Cytarabine (Ara-C) and Cyclophosphamide (Cy) was used for conditioning of patients with chronic granulocytic leukemia (CGL). Using this conditioning treatment, fewer transplant related complications, including acute GVHD, VOD and severe infections, were observed. Acute GVHD did not develop, but chronic GVHD, accompanied with graft-versus leukemia, was present in half of the cases. To determine the clinical effect of the DBM/Ara-C/Cy conditioning, the recovery of peripheral blood lymphocytes was examined after allogeneic BMT for patients with CGL in comparison with TBI/Cy conditioning. The lymphocyte subsets of 11 DBM patients were followed and analyzed periodically (30-90 days, 4-12 months and > 13 months) using ten monoclonal antibodies and flow cytometry. Decreased percentage of total T cells as well as CD4+ and CD8+ subpopulations, significantly decreased T cell activation and increased proportion of TCR gamma delta + cells were found to be characteristic in the early post-transplant period in the DBM group. Early recovery and consistently higher percentage of B cells were observed for the whole follow-up period of patients receiving DBM conditioning. A high proportion of NK cells was observed in all transplant recipients. These findings suggest that the characteristic pattern of recovering lymphocytes is associated with the lack of severe transplant-related clinical complications following DBM/Ara-C/Cy conditioning.

Adolescent↗
PubMed1993

Non-supralethal mitobronitol/cytarabine/cyclophosphamide conditioning without irradiation before bone marrow transplantation for accelerated chronic granulocytic leukemia: apparent absence of acute graft-versus-host disease.

Cytostatic chemotherapy instead of supralethal total body irradiation (TBI) has been increasingly used as an alternative myeloablative regimen before bone marrow transplantation (BMT). While irreversible azoospermia/amenorrhoea seems to occur less frequently with such conditioning, graft-versus-host disease (GVHD) remains unaffected. Five-year disease-free survival in accelerated chronic granulocytic leukemia (CGL), after BMT with matched sibling grafts has been 0.10-0.30. Mitobronitol, cytosine arabinoside, and cyclophosphamide were used for conditioning. Patients were transplanted with unmanipulated HLA/MLC identical sibling bone marrow. For recovery, a pathogen-low room was available without air filtering and laminar airflow. Seven of eight accelerated-CGL patients were engrafted: full allogeneic reconstitution was detected in four and mixed chimerism in three patients. Five out of the seven engrafted patients survived at least nine months (median = 42 months), two are considered cured (8-9 years survival). The four leukemia-free survivors displayed full allogeneic reconstitution and presented symptoms of chronic GVHD. One patient became a genetically verified father. Acute GVHD and veno-occlusive liver disease (VOLD) were absent in all patients, diffuse interstitial pneumonitis (IP) occurred in one case. Non-supralethal conditioning with mitobronitol/cytarabine/cyclophosphamide in accelerated-CGL allows allogeneic bone marrow reconstitution with survival and cure rates comparable to those achieved with other protocols using TBI or busulphan conditioning. Unlike the latter treatments, however, our protocol leads to fewer transplant-related complications including acute GVHD, IP, VOLD, and azoospermia/amenorrhoea.

Adult↗
PubMed1991

[Amphotericin B resistant severe hepato-splenic candidiasis, responding to fluconazole, in a patient following bone marrow transplantation].

A 23 year old woman with Philadelphia-positive chronic granulocytic leukaemia underwent a 3/4 HLA identical bone marrow transplantation. During the neutropenic period, a septic condition developed which was caused by Candida albicans. Administration of Amphotericin B for 63 day was ineffective including an attempt to give the drug through the truncus coeliacus. Finally the sepsis disappeared during fluconazole treatment.

Adult↗
PubMed1976

An assay for selecting high risk population for gastric cancer by studying environmental factors.

Gastric cancer mortality incidence data registered in two different areas of Eastern Transylvania (Roumania) were reported related to 325,000 inhabitants from the period of 1951-1972. The findings were compared to some geographical environmental factors deriving from an area of 13,300 km with 905,700 inhabitants. A 2-3.5 times larger incidence of gastric cancer (75-140 per 100,000/year) was found in some selected geographical areas of the intermontane depressions of Gheorgheni and Ciuc in comparison to hilly area of Transylvanian Tableland. The difference might be explained by some unknown environmental gastric cancer risk factors. Of the natural factors, the presence of magmatic substrata shows a significant degree of correlation. The main pedological factor seems to be badly drained pseudoglyied podzolic and peaty soils of low pH and high content of organic matter. Sofs drinking waters also may be involved as risk factor. High altitude, cold climate determining a restricted assortiment of cultivated plants, the successive production of vegetal and animal food on the same soil for livelong periods and several generations, especially in isolated rural areas, seem to represent gastric cancer risk factors. According to authors' opinion a survey of the high-risk population selected on the basis of the environmental factors, especially of the persons suffering from gastric disorders considered today possible precursors of gastric cancer, may offer some progress in detecting early gastric malignancy in the future.

Climate↗
PubMedDate not supplied

Apolipoprotein E polymorphism in Pick's disease and in Huntington's disease.

The polymorphism of apolipoprotein E (apoE) has been recognized as a genetic risk factor in different neurodegenerative disorders, with or without tau protein- related neuropathology, but few published epidemiological data are available as concerns the association of different apoE alleles with two relatively rare forms of dementia, Pick's disease (PiD) and Huntington's disease (HD). In this study the frequency of the apoE4 allele was examined in 36 persons with histopathologically proven PiD and compared with that of the apoE genotype in 28 HD probands and 79 aged healthy controls. The E4 allele was overrepresented selectively in PiD (42%) as compared with the control population (7%). No such association was found for HD probands (9%). This finding lends further support to the hypothesis that the E4 genotype is not an Alzheimer's disease specific susceptibility factor, and that it could be present in diverse dementing disorders with tau protein related neuropathology, such as PiD.

Aged↗
PubMedDate not supplied

Parallel functional and immunological detection of human multidrug resistance proteins, P-glycoprotein and MRP1.

The proper assessment of the expression and drug extrusion activity of multidrug resistance proteins in various tumor cells is a challenging clinical laboratory problem. Recently, we have introduced a fluorescent dye (calcein) accumulation assay for the estimation of the functional expression of both P-glycoprotein (MDR1) and the multidrug resistance-associated protein (MRP1). Since both MDR1 and MRP1 decrease the intracellular accumulation of the fluorescent free calcein, by applying appropriate inhibitors of MDR1 and MRP1, the transport activity of these proteins could be quantitatively and selectively estimated in fluorometry or flow-cytometry assays. In the present work single-cell fluorescence digital imaging has been applied to characterize the kinetics and inhibitor-sensitivity of calcein accumulation in a mixture of HL60 MRP1 and NIH 3T3 MDR1 cells. Subsequent immunofluorescence labeling was performed by the anti-MDR1 monoclonal antibody (mAb) UIC2 in the same cell population. We report that the double labeling approach, based on the single cell calcein accumulation assay and an immunofluorescence detection, provides good sensitivity and selectivity for the simultaneous functional and immunological detection of cellular MDR1 and MRP1.

3T3 Cells↗