Biomedical subjects
Publications and source records attributed to L Sokol.
Choriocarcinoma represents the most serious form of trophoblast gestation disease. In the majority of cases the carcinomatous tissues fill out the uterine cavity, or they grow in a form of nodes deep in the uterine wall. The primary extrauterine localization of this tumour is very rare. The authors describe two cases of choriocarcinomas with tubal or ovarian localization. (Fig. 4, Ref. 19.)
The authors compared in a group of 273 symptomatic patients the effectiveness of palpation and transabdominal USG of the prostate and in a group of 162 patients palpation and transrectal USG of the prostate in diagnosing of prostate carcinoma. Histopathological correlation was available in 203 (74.4%) patients, all of them examined by transrectal USG. From the whole group of 273 patients prostate carcinoma was confirmed in 69 (25.3%). Based on USG examination alone prostate cancer was proved by histopathological methods in three (4.3%) patients with a negative finding on palpation. A disappointment of the USG method was that it did not prove possible to diagnose before operation incidental cancer in 14 (20.3%) patients with BPH. USG made it possible to define more accurately the stage of cancer in groups T2 and T3. The effectiveness was assessed as follows: sensitivity, specificity and total accuracy during palpation was 75.4%, 88.8%, 84.2%, in transabdominal USG: 78.3%, 91.8%, 87.2% and in transrectal USG of the prostated 97.7%, 90.7% and the overall accuracy 92.6%. Despite these results for screening of patients with prostate cancer USG of the prostate can be recommended only after palpation and PSA examination.
The term familial and congenital polycythemia encompasses a heterogeneous group of disorders with the common characteristic of an absolute increased red cell mass since birth and/or similar phenotype also present in relatives. In the last 2 decades the differential diagnosis between primary and secondary familial polycythemias became more physiologically relevant as new sensitive techniques, such as accurate measurements of serum erythropoietin (S-EPO) concentration by radioimmunoassay (RIA) or ELISA, and assessment of growth of erythroid progenitor cells in vitro became available. Consequently, correct classification of many older previous reports of familial polycythemias is difficult. While familial secondary polycythemias due to high oxygen affinity hemoglobin mutants are not infrequent and have been well delineated in terms of molecular pathophysiology and phenotype during the last 3 decades, those secondary familial polycythemias due to 2,3 DPG deficiency are very rare. Familial and congenital polycythemias with increased EPO concentration and normal arterial oxygen saturation and oxygen dissociation kinetics represent an intriguing group of disorders wherein the molecular lesions remain obscure; however, in some instances a possibility of abnormal oxygen sensing pathway involving hypoxia inducible factor-1 (HIF-1) open an intriguing yet unexplored area of hematology and biology. In contrast the primary familial and congenital polycythemia (PFCP) has been only recently recognized (the first report published in 1977). Various designations have been used in the past to describe PFCP, a rare clinical syndrome, including: benign familial erythrocytosis, polycythemia vera of childhood, primary polycythemia, pure erythrocytosis, etc. Some of these terms stressed the relatively benign, non-progressive course of the disease with a normal lifespan of affected subjects; however, the apparent benignity of some of these disorders has been questioned. These disorders are familial and/or congenital, and the clinical and laboratory evidence of secondary polycythemias must be excluded. Only about 2 dozen familial and sporadic cases with PFCP have been reported. However, the mutations of erythropoietin receptor (EPOR) found in some of families with PFCP represent the only defined molecular defect of primary polycythemic phenotypes. All reported PFCP associated EPOR mutations result in truncation of its intracytoplasmic C-terminal domain which negatively regulates the EPO/EPOR signal transduction pathway. Subjects with these mutations have decreased or normal S-EPO and increased sensitivity of erythroid progenitor cells to low EPO concentrations in in vitro assays. Mutations of other genes involved in post EPOR signaling pathway such as JAK-2, HCP and STAT 5 may also play a causative role in pathogenesis of some of PFCP families where mutation of EPOR was not found.
Chromosome 19 is short but has higher relative density of genes than other chromosomes. Increasing number of the genes coding for proteins implicated in the pathogenesis of various human diseases have been mapped on chromosome 19. Mutations of low density lipoprotein receptor (LDL-R) result in one of the most frequent mendelian inherited disorder-familial hypercholesterolemia. Mutations of insulin receptor (INSR) are causative for rare syndromes of insulin resistance and some of non insulin dependent diabetes mellitus (NIDDM). Erythropoietin receptor (EPOR) mutations are causative for rare primary familial and congenital polycythemias (PFCP). Defects of one of the largest gene in the human genome RYR 1 (ryanodine receptor gene) (> 240 kb in size) accounts for majority of malignant hyperthermia (MH) and central core disease (CCD). All these disorders represent group of receptor diseases. The amplification of GCT trinucleotide repeats in myotonic dystrophy protein kinase (DMPK) gene is causative for myotonic dystrophy (DM) and represents a new class of human gene mutations: trinucleotide repeat mutations. Apolipoprotein E (APOE) locus plays a role in pathogenesis of the late onset familial Alzheimer's disease. Translocation of EA2 gene which encodes two helix-loop-helix (HLH) transcription proteins and its fusion with PBXI or hepatic leukemia factor (HLF) leads to the leukemogenesis in subgroup of ALL. Interestingly adeno-associated virus (AAV), currently widely used as vector for gene therapy has unique capability of specific integration into human chromosome 19q.
Primary familial and congenital polycythemia (PFCP) is characterized by erythrocytosis with normal arterial PO2, blood P50, and serum erythropoietin (EPO) levels. In two PFCP families EPO receptor (EPOR) polymorphisms cosegregated with PFCP. A heterozygous insertion of G at EPOR nucleotide 5975 was identified in genomic DNA from polycythemic members of family no. 2. 5974insG shifts the reading frame at codon 430, predicting amino acid substitutions and truncation of the last 64 amino acids. Wild-type and mutant EPOR transcripts were detected in erythroid progenitors from affected individuals. Burst-forming units-erythroid from patients exhibited increased colony size and sensitivity to EPO. Transfected Ba/F3 cells expressing EPOR 5974insG exhibited increased EPO sensitivity compared with cells expressing wild-type EPOR. The functional effect of this EPOR mutation was directly compared with the other C-terminal mutations reported in unrelated PFCP families by expression in Ba/F3 cells. The transfected cells with another primary polycythemia associated EPOR mutant construct (G6002A) also exhibited increased sensitivity to EPO.
Juvenile chronic myelogenous leukemia (JCML) is a myeloproliferative disease in which morbidity and mortality are primarily caused by nonhematopoietic organ failure from myelomonocytic infiltration or by failure of the normal bone marrow. Morphologic evidence of maturation arrest, karyotypic abnormalities, and progression to blast crisis are infrequent events. Viral infections and other reactive processes can initially mimic the clinical course of JCML, creating diagnostic problems. Because of the rarity of JCML and technical limitations, formal clonality studies have not been reported previously. Nine female JCML patients were identified by clinical criteria, characteristic 'spontaneous' in vitro cell growth, and negative cultures and titers for various viral agents. Peripheral blood and bone marrow samples were obtained at the time of diagnosis for cell separation and RNA and DNA isolation. To assess clonality, X-chromosome inactivation patterns were evaluated using three different, recently developed polymerase chain reaction-based clonality assays. All nine female JCML patients showed evidence for monoclonal origin of mononuclear cells at the time of diagnosis. Cell separation studies further traced the monoclonal origin back to at least the most primitive myeloid progenitor cell. Reversion to a polyclonal state was demonstrated after bone marrow transplant and also in one patient following treatment with 13-cis retinoic acid. This demonstration of clonality in JCML delineates it from the reactive processes and provides a basis for molecular genetic strategies to identify causally associated mutations.
BACKGROUND: Clonal proliferation of monocytoid B-lymphocytes (MBLy)--monocytoid B-cell lymphoma (MBCL) represents a "new" type of lymphoma within the spectrum of B-cell malignancies. OBJECTIVES: The aim of the study was to evaluate the possibilities of a routine histological and immunohistochemical diagnosis of MBCL. METHODS: Three cases of MBCL diagnosed in peripheral lymph nodes (n = 2) and in mammary gland with infiltration of regional lymph node (n = 1) were analyzed both histologically and immunohistochemically using a panel approach (Ig chains, CD30 antigen, markers of B-cells, T-cells and of monocytes/histiocytes). RESULTS: Morphological appearance of neoplastic cells of MBCL is identical to that of MBLy in reactive conditions--kidney-shaped nuclei, bright clear PAS-negative cytoplasm, and small inconspicuous nucleoli. CONCLUSIONS: Morphological appearance together with immunophenotypic results (positivity of CD20 and Ki-B5, negativity of CD3, CD43, CD45RO, and of lysozyme, negativity of CD30) are considered to represent sufficient diagnostic criteria of MBCL, including its differential diagnosis of other B-cell low grade malignancies. An increase of large cell type MBLy might represent a feature of a secondary blastic transformation of MBCL. (Tab. 2, Fig. 5, Ref. 27.)
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Oncocytoma includes 3-5% of all renal tumors. It does not manifest itself by typical symptoms and often is diagnostically confirmed in coincidence with examinations of other diseases. The preoperative diagnosis of oncocytoma is difficult. Oncocytoma must be taken into consideration in cases of bilateral multilocular tumors of the kidney. Neither RTG, USG and CT examinations, nor angiography give the specific picture of oncocytoma. One of the possibilities of diagnosis confirmation is the peroperative biopsy. If the latter confirms the diagnosis, then according to possibilities, operation with maintenance of unimpaired renal parenchyme should be performed. The prognosis of the disease is good and depends on the stage of cellular differentiation of tumor. The study presents observations of 4 patients subdued to surgery at the Urologic Clinic FHwP in Kosice since 1981 to 1990. The patients survive without metastases for 3-4 years.
The authors reflect on the importance of interdisciplinary collaboration when resolving problems of the diagnosis and treatment of diseases of the thyroid gland. In 1989-1993 at the First Surgical Clinic of the Kosice Hospital 189 patients were operated on account of thyroid disease. During the last year the number of operations increased substantially due to better cooperation. In their group eufunctional nodular goitre was indicated most frequently for surgery. In the diagnosis they preferred ultrasonography and needle aspiration cytology. Peroperative biopsy is used in every operation of the thyroid gland. If the USG and cytological finding are not clear, they perform hemothyroidectomy and send the material to a pathologist for evaluation. By intensive interdisciplinary collaboration they achieved a very low number of two-stage operations in carcinoma, 1.05% paralyses of the recurrent nerve and a 1.58% postoperative mortality.
The authors present a report on a new clinical and pathological entity--aggressive angiomyxoma which was described in 1983. They draw attention to the genesis of this tumour and its macro- and microscopic picture. They emphasize that treatment of this tumour involves its complete surgical extirpation and frequent local relapses without secondaries. The authors describe in detail two of their observations of aggressive angiomyxoma in a 32- an 38-year-old woman where the tumour started in the lesser pelvis. In both instances, despite radical extirpation of the tumour, within a relatively short time a local relapse developed detected by USG and CT without clinical symptoms.
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A 42-year-old Caucasian male with sporadic primary polycythemia has been followed by us for 13 years. During the time of observation, his hemoglobin had been stable, and he has never had an elevated white count or platelet count or any other stigmata of polycythemia vera (PV). Both of his parents, his three children, and all siblings have been hematologically normal. The in vitro culture of erythroid progenitors revealed an absence of autonomous erythropoietin (Epo)-independent erythroid colonies but demonstrated a marked increase in the sensitivity of erythroid progenitors to Epo. We have undertaken a study designed to determine whether a mutation in the Epo receptor (Epo-R) gene could cause the polycythemia phenotype seen in either dominant or recessive primary polycythemia described by us and others, or in polycythemia vera. We have sequenced the cytoplasmic positive and negative regulatory domains of the Epo-R genomic DNA, and a transversion of C to T in nucleotide 6148 was found in one of the patient's chromosomes. This mutation is located in the negative regulatory domain and results in a change from proline to serine (P488S). We have subsequently analyzed more than 40 chromosomes from unrelated normal subjects, as well as autosomal dominant, recessive, and sporadic primary polycythemia and polycythemia vera subjects. In no instance was the same or any other mutation in the Epo-R found. To determine if this Epo-R mutation is a cause of increased sensitivity of erythroid progenitors to erythropoietin, Ba/F3 cells (interleukin-3-dependent murine lymphoid line) were transfected with normal and mutated Epo-R cDNA, rendering the transfected cells viable and able to proliferate in Epo. Transfectants with wild-type and mutant Epo-R cDNA exhibited no difference in the presence of Epo. More recently, we were able to obtain DNA from the seven family members of the propositus and found that the nonpolycythemic mother and one of the siblings have the same Epo-R mutation. We conclude that this first described mutation of Epo-R encountered in humans does not appear on its own to explain the polycythemia phenotype; however, the possibility that it may interact with some other acquired or congenital abnormality in generating the polycythemia phenotype cannot be excluded.
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The authors prospectively and retrospectively mutually compared the diagnostic value of urography, ultrasonography (USG), and computer tomography (CT) in four patients, with the diagnosis misstated prior to operation. The most valuable findings were provided by CT. Mere utilization of these methods does not exclude the possibility of diagnostic misstatements. In three patients the ultimate diagnosis was assessed on the basis of operative revision and in one patient, by means of cytologic examination of the renal punctate. Owing to retrospective evaluation of examinations, diagnostically valuable symptoms which could have lead to the correct diagnosis, were distinguished. Hence, examinations must necessarily be evaluated in complex with the general clinical state. (Fig. 6, Ref. 14.).
The authors present an account on a neonate with dextro-lateral renal venous thrombosis. They focus attention on the diagnostic and therapeutic procedure and compare it with available data from the literature. Contrary to data in the literature, they did not observe in the acute stage of renal venous thrombosis signs of disseminated intravascular coagulation in peripheral blood. It did not prove possible to elucidate the action of any of the factors leading to the development of renal venous thrombosis. After evidence of permanent functional loss of the right kidney nephrectomy was performed. Histopathological examination provided evidence of obliterating thrombosis of the renal veins with partial recanalization and calcifications. The authors emphasize the necessity of early diagnosis of renal venous thrombosis and adequate treatment based on the revealed findings.
The authors examined, using the method of flow cytometry, 56 children with acute lymphoblastic leukaemia. Leukaemic cells of the bone marrow aspirate and peripheral blood were examined on a FACS 440 apparatus for establishment of the diagnosis before treatment was initiated. Individual immunological subtypes were differentiated by means of a panel of monoclonal antibodies. 80.5% of acute lymphoblastic leukaemias originated from different developmental stages of B cells, 12.5% were formed by leukaemias from T cells and 7% were non-differentiated leukaemias. The mean follow-up period in the group was 33 months. According to the therapeutic results children with leukaemia ensuing from precursors of B cells had a more favourable prognosis than children with T leukaemia and children with non-differentiated leukaemia. Quantitative examination of nuclear DNA of leukaemic cells revealed in 55% of the patients of the group aneuploidy with clear predominance of hyperdiploidy, 45% of the patients suffered from diploidy. The least number of relapses was recorded in the investigation period in children with hyperploid acute lymphoblastic leukaemia. The proliferating activity of leukaemic blasts was expressed by the number of cells in the S + G2M stage of the cellular cycle and was higher in the bone marrow than in peripheral blood but did not differ in individual immunological subtypes or in diploid leukaemias. The authors were not able to prove its prognostic importance. Flow cytometry is a rapid and sensitive diagnostic method which makes it possible to characterize more satisfactorily the heterogeneous group of acute lymphoblastic leukaemias.