Biomedical subjects

M Kos

Publications and source records attributed to M Kos.

At least 37 records · Page 2Linked to original sources

PubMed2001

Congenital gastrointestinal system malformations in a 5-year post mortem series.

The aim of this study was to determine the types and frequencies of congenital gastroinstestinal (G-I) tract malformations on post mortem in the period from 1996 to 2000. Autopsy protocols of aborted fetuses, stillborn infants and infants that died within 7 days after delivery were retrieved from the archive and studied. Cases of cleft lip and/or palate, biliary tract, pancreatic and diaphragmal malformations were not included in the study. During the mentioned period, 1251 autopsy was performed with 127 showing some malformation. G-I tract malformation was diagnosed in 37 cases (2.9% and 29.1%, respectively). Most frequent malformations were atresias at the different level of the G-I tract (56.75%), followed by omphalocoele (35.13%) and gastroschisis (8.1%). Of atresias, the most frequent were oesophageal and anorectal (38.1% of atresias, each). A striking male preponderance (2.36:1) in the frequency of G-I malformations was noticed. Isolated G-I malformations were found in 32.4%, different but simultaneous G-I malformations in 5.4% and association with other organ system(s) malformations in 62.2%. Omphalocoele and anorectal atresia were associated with other organ system malformation(s) in 34.8%, each. Other organ systems affected by malformation besides the G-I tract were cardiovascular system (65.21%), urogenital system (also 65.2%), gastrointestinal system with the malformation of another kind or atresia at the different level (17.4%), CNS (17.4%), skeletal system (26.1%) and other organs or systems (30.7%).

Autopsy↗

PubMed2000

Identification of a new isoform of the human estrogen receptor-alpha (hER-alpha) that is encoded by distinct transcripts and that is able to repress hER-alpha activation function 1.

A new isoform of the human estrogen receptor-alpha (hER-alpha) has been identified and characterized. This 46 kDa isoform (hERalpha46) lacks the N-terminal 173 amino acids present in the previously characterized 66 kDa isoform (hERalpha66). hERalpha46 is encoded by a new class of hER-alpha transcript that lacks the first coding exon (exon 1A) of the ER-alpha gene. We demonstrated that these Delta1A hER-alpha transcripts originate from the E and F hER-alpha promoters and are produced by the splicing of exon 1E directly to exon 2. Functional analysis of hERalpha46 showed that, in a cell context sensitive to the transactivation function AF-2, this receptor is an effective ligand-inducible transcription factor. In contrast, hERalpha46 is a powerful inhibitor of hERalpha66 in a cell context where the transactivating function of AF-1 predominates over AF-2. The mechanisms by which the AF-1 dominant-negative action is exerted may involve heterodimeri zation of the two receptor isoforms and/or direct competition for the ER-alpha DNA-binding site. hERalpha66/hERalpha46 ratios change with the cell growth status of the breast carcinoma cell line MCF7, suggesting a role of hERalpha46 in cellular proliferation.

Base Sequence↗

PubMed2000

DNA ploidy analysis and cell proliferation in congenital sacrococcygeal teratomas.

BACKGROUND: Congenital sacrococcygeal teratoma is the most common germ cell tumor in infants and children. It usually is diagnosed at birth, is benign, and consists of fully differentiated mature tissues. Congenital sacrococcygeal teratomas (SCTs) also may contain immature tissues, most commonly of neural origin. The proportion of malignant teratomas increases with advancing age, but the relation between mature and immature SCTs is not well understood. Thus, it is very important to determine proliferative activity, DNA ploidy, and DNA index to predict biologic behavior of these tumors. METHODS: DNA ploidy and cell proliferation were analyzed by flow cytometry, and the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 were analyzed immunohistochemically on paraffin embedded tissue. RESULTS: All the tumors that were surgically treated within 3 months after birth, including immature teratoma, were diploid. Strongly positive PCNA immunostaining was found in both immature teratomas, and weakly positive PCNA was found in nine cases. Weak positivity for Ki-67 was observed in 2 cases, and moderate positivity was observed in 6 cases including immature teratomas. CONCLUSION: The value of flow cytometry in the prediction of biologic behavior of congenital SCT should be analyzed further. Our results suggest that Ki-67 and especially PCNA may reflect the proliferative activity of these tumors.

Cell Division↗

PubMed2000

Tissue-specific expression of multiple mRNA variants of the mouse estrogen receptor alpha gene.

The isolation of five new mouse estrogen receptor alpha mRNA variants (mERalpha A, B, F1, F2 and H) is described. All of these transcripts are generated by alternative splicing and all encode the 66 kDa ERalpha protein that the previously identified mRNA C variant generates. However, these transcripts differ in their 5' untranslated regions. RT-PCR and S1 nuclease protection assays revealed a tissue- and sex-specific expression pattern of all variants. The C and F mRNA variants are the predominantly expressed mERalpha variants in mouse. The expression of mERalpha H mRNA is restricted to liver, although female mice produce around a five fold higher level of this transcript than males. Our results show that the mERalpha gene is a complex genomic unit in mice that exhibits alternative splicing which is regulated in a tissue-specific manner.

5' Untranslated Regions↗

PubMed2000

Neutrophil antigen 5b is carried by a protein, migrating from 70 to 95 kDa, and may be involved in neonatal alloimmune neutropenia.

BACKGROUND: Neutrophil antigen 5b has been described as involved in transfusion reactions and not in neonatal alloimmune neutropenia. CASE REPORT: Anti-5b was found in the serum of a mother of a persistently neutropenic newborn, who had several bacterial infections. The neutropenia responded to treatment with recombinant human granulocyte-colony-stimulating factor. Immunoprecipitation experiments performed with this and three other 5b antisera identified a protein, migrating from 70 to 95 kDa, as carrier of 5b. The observed pattern of migration may point to heavy glycosylation of this protein. RESULTS: Six 5b-negative donors were identified among 54 screened white donors, for a 5b gene frequency of 0.66. CONCLUSION: Alloimmunization to 5b in pregnancy is rare. In the patients with neonatal neutropenia analyzed in the last decade, this was the first case discovered.

Antigens↗

PubMed2000

Analysis of Bcl-2 protein expression in chronic lymphocytic leukemia. A comparison of three semiquantitation techniques.

A number of studies revealed that high expression of the proto-oncogene bcl-2 correlated with poor prognosis or resistance to chemotherapy in some tumors but predicted a favorable clinical course in other neoplasias. In these studies, however, different immunologic techniques for Bcl-2 detection were used, raising the question of whether the methods applied were comparable. Using chronic lymphocytic leukemia (CLL) cells, the aims of our study were as follows: (1) to determine the reproducibility of Bcl-2 semiquantitation by immunocytochemistry, flow cytometry, or immunoblotting; (2) to study the agreement between results obtained by these methods; and (3) to examine the association between Bcl-2 expression in tumor cells of 99 patients with CLL and clinical parameters. We found that determination of Bcl-2 expression by immunocytochemistry was reproducible and the results were comparable with those of flow cytometry and immunoblotting. In the patient collective examined, Bcl-2 expression did not reflect the extent of tumor mass, but higher levels were found more often in patients with progressive disease.

Flow Cytometry↗

PubMed2000

Three-dimensional sonography in prenatal diagnosis: a luxury or a necessity?

Three-dimensional sonography revolutionized ultrasound imaging with its capacity to depict an unlimited number of planes in which the object of interest can be displayed. The addition of numerous modalities of image rendering promotes three-dimensional sonography to the top of the spectrum of diagnostic imaging in obstetrics and gynecology. The aim of this article is to present our experience in 3-D sonography during the second and third trimester of pregnancy and to give a comparative review of literature. 247 patients in gestational age ranging from 12 to 40 weeks of gestation were examined over a three year period. The majority of patients entered the study because fetal anomaly was suspected at two-dimensional sonography. Some patients were sent on to three-dimensional sonography because it was not possible to depict clearly normal fetal anatomy by two dimensional sonography. Out of 170 fetal anomalies three-dimensional sonographic analysis failed in only three cases. In all three anomaly was accompanied with severe oligohydramnios. Main advantages of three-dimensional ultrasound in perinatal medicine and antenatal diagnosis include scanning in the coronal plane, improved assessment of complex anatomic structures, surface analysis of minor defects, volumetric measuring of organs, "plastic" transparent imaging of fetal skeleton, spatial presentation of blood flow arborization and, finally, storage of scanned volumes and images. It is our decided opinion that three-dimensional sonography has gained a valuable place in prenatal diagnosis, becoming a necessity for every modern perinatal unit.

Congenital Abnormalities↗

PubMed2000

The ultrastructure of photoreceptor cells in the pineal organ of the blind cave salamander, Proteus anguinus (Amphibia, Urodela).

We studied ultrastructure of the photoreceptor cells in the pineal organ of blind, depigmented, neotenic cave salamander, Proteus anguinus. Unlike in epigean vertebrates the outer segments of most photoreceptor cells consists of concentrically arranged lamellae, however; in few cells, the outer segments contain 7-9 plasma membrane disks. In both types of photoreceptor cells the outer segments enclose lumps of vesicles of different sizes. The photoreceptor cells of Proteus anguinus are similar to those in other cavernicolous fish species.

Animals↗

PubMed1999

Self-diffusion imaging by spin echo in Earth's magnetic field.

The NMR of the Earth's magnetic field is used for diffusion-weighted imaging of phantoms. Due to a weak Larmor field, care needs to be taken regarding the use of the usual high field assumption in calculating the effect of the applied inhomogeneous magnetic field. The usual definition of the magnetic field gradient must be replaced by a generalized formula valid when the strength of a nonuniform magnetic field and a Larmor field are comparable (J. Stepisnik, Z. Phys. Chem. 190, 51-62 (1995)). It turns out that the expression for spin echo attenuation is identical to the well-known Torrey formula only when the applied nonuniform field has a proper symmetry. This kind of problem may occur in a strong Larmor field as well as when the slow diffusion rate of particles needs an extremely strong gradient to be applied. The measurements of the geomagnetic field NMR demonstrate the usefulness of the method for diffusion and flow-weighted imaging.

1-Propanol↗

PubMed1999

First trimester malformation screening.

First trimester fetal malformation screening still represents a diagnostic challenge in modem obstetrics. Being solely dependent on ultrasound instrumentation, and the skill and experience of the operator, recently improved by introducing high frequency transvaginal approach and digital image processing. This opens a new field of ultrasound in obstetrics called sonoembriology. Until now sonoembriology in routine clinical practice resulted in numerous reports about early detection of rare anomalies and uncommon syndromes. The reported sensitivity of sonoembriology with a respect to a final pregnancy outcome was more than 60% of all malformations in total, while in combination with ultrasound screening in second trimester, increases to in excess of 80%. The commonest anomalies detected by sonoembriology are anomalies of the head and brain, heart, abdominal wall, unbilical cord, urinary tract and skeleton. There is an important role of sonoembriology in the assessment of the nuchal translucency in the screening programme for chromosomal anomalies. This changes the well-known concept "fetus as a patient" to "embryo as a patient" and opens new frontiers in fetal diagnosis and therapy.

Congenital Abnormalities↗

PubMed1999

Ultrasonic markers of fetal chromosomal abnormalities.

OBJECTIVE: The aim of this brief investigation was to correlate the most common sonographically detectable markers with certain type of chromosomal disorder diagnosed by available karyotyping procedures. STUDY DESIGN: During the 3 year study period fetal karyotyping was performed in 1055 patients for a variety of clinical indication. Twenty one percent (21%; 222/1055) of procedures were done because of sonographically detectable structural disorders related to phenotype expression of chromosomopathies. Sonographic examinations and karyotyping procedures were performed between the 10th and 36th week. The average maternal age was 27 years, unselected. RESULTS: The fetal karyotype was abnormal in 13.5% of cases (30/222). Within the group of single marker, 11.6% (7/60) of karyotypes were abnormal. Multiple markers of chromosomal abnormalities resulted in 14.2% (23/162) of abnormal karyotypes. The most frequent chromosomal disorder detected in sonographic screening is trisomy 18 (50%; 15/30). The data on the frequency of different types of chromosomal abnormalities are given. CONCLUSIONS: The incidence of chromosomal abnormalities for ultrasonographically detectable malformations is much higher than the incidence reported in screening studies based on maternal age or biochemical screening. Trisomy 21 showed the relative lack of variety in phenotypic expression, and nuchal translucency screening has to be accepted rationally. Associated numerous major and minor malformations were the most prominent factors leading to the diagnosis of chromosomopathies, particularly trisomy 18.

Adolescent↗

PubMed1999

The study of morphology and circulation of early embryo by three-dimensional ultrasound and power Doppler.

Three-dimensional (3-D) ultrasound plays an important role in obstetrics predominantly for assessing fetal anatomy. Presenting volume data in a standard anatomic orientation assists both ultrasonographers and pregnant patients to recognize anatomy more readily. Three-dimensional ultrasound is advantageous for the study of normal embryonic and/or fetal development, as well as providing information for families at risk for specific congenital anomalies by confirming normality. This method offers advantages in assessing the embryo in the first trimester as it is able to obtain multiplanar images through endovaginal volume acquisition. Rotation of the embryo and close scrutiny of the volume allow the systematic review of anatomic structures such as cord insertion, limb buds, cerebral cavities, stomach and bladder. Using this modality one can easily obtain the volumes of the gestational sac and yolk sac and can evaluate their relationship to prediction of pregnancy outcome. Three-dimensional power Doppler sonography has the potential to study process of placentation and evaluate the development of the embryonic and fetal cardiovascular systems. Three-dimensional ultrasound imaging in vivo compliments pathologic and histologic evaluation of the developing embryo, giving rise to a new term: 3-D sonoembryology. Rapid technological development will allow real-time 3-D ultrasound to provide improved and expanded patient care on the one side, and increased knowledge of developmental anatomy on the another.

Female↗

PubMed1999

Changes of E-cadherin and beta-catenin levels during induced differentiation of colorectal carcinoma cells.

Following the finding of a great increase in cell-cell adhesion in several colorectal carcinoma cell lines after induced differentiation, the expression of E-cadherin-catenin complexes was analyzed. The sensitivity of cell lines to the differentiation induced by sodium butyrate differed. Nevertheless, all cells growing for 5 days in the medium containing 2 mM sodium butyrate changed their morphology and adherent properties. The expression of E-cadherin and catenins participating in its function were analyzed. A significant increase in E-cadherin level after butyrate treatment was found in HT29 and LS174T cell lines only. However, a high decrease in beta-catenin level was detected in all cell lines treated with butyrate. Further analysis showed regulation of beta-catenin at the level of mRNA.

Blotting, Northern↗

PubMed1998

Ultrasound screening for fetal anomalies in developing countries: wish or reality?

The main problems related to the screening of fetal anomalies in developing countries do include general ones of limited resources for health care and specific ones related to ultrasonographic practice, education, and instrumentation. The strategy to improve the detection of fetal anomalies is reliable, but has to be targeted to the following cornerstones: maintenance of obligate minimum of quality in perinatal care, establishment of three ultrasonographic examinations as a basic prerequisite of antenatal care, enhanced importance of first trimester screening, and a uniform program of education of sonographers, emphasizing the standardization of basic examination. Because of limited resources for perinatal care, we have to be highly responsible in selection of echographic instrumentation and appropriate education, subject to rigorous cost-benefit analysis.

Algorithms↗

PubMed1998

Differential sensitivity of CD4+ and CD8+ T lymphocytes to the killing efficacy of Fas (Apo-1/CD95) ligand+ tumor cells in B chronic lymphocytic leukemia.

B-chronic lymphocytic leukemia (B-CLL) is characterized by cellular and humoral immune defects resulting in increased rates of infection and disturbed immune surveillance against cancer cells as well as by the expansion of slowly proliferating tumor cells. We found increased Fas receptor (FasR) expression in peripheral blood CD4+ and CD8+ cells of B-CLL patients compared with the equivalent cells of healthy donors. Although increased Fas receptor expression was significant in both T-lymphocytic subsets, only CD4+ cells from B-CLL patients underwent apoptosis after treatment with the agonistic Fas antibody CH11. In CD4+ cells of B-CLL patients, the Fas-sensitivity also correlated with a CD4+/CD8+ ratio below the lower threshold of healthy individuals (<1.0). By contrast, FasR expression in the CD19(+) fraction of B-CLL patients was downregulated compared with normal controls, and this was associated with an insensitivity to CH11-induced apoptosis. The B-CLL cell line EHEB as well as CD19(+) cells from B-CLL patients constitutively expressed Fas ligand (FasL). The FasL was functionally active, as the B-CLL cell line as well as T-cell-depleted CD19+ B-CLL fractions were able to kill target T-acute lymphatic leukemia (T-ALL) cells in vitro. This effect was inhibited by the antagonistic FasR-antibody ZB4, the neutralizing anti-FasL monoclonal antibody (MoAb) NOK-2 or by transfection of the caspase inhibitor crmA. These data point to the fact that expression of FasL on CD19(+) B-CLL cells, together with enhanced susceptibility of CD4+ T cells toward FasL-bearing effector cells, are causally linked to the relative reduction of CD4+ cells occurring during B-CLL progression. These findings could explain the inversion of the ratio of CD4+/CD8+ cell numbers, which may be causally linked to the immune deficiency observed in these patients and to the expansion of the neoplastic clone in B-CLL.

Aged↗

PubMed1998

Functional granulocyte/macrophage colony stimulating factor receptor is constitutively expressed on neoplastic plasma cells and mediates tumour cell longevity.

It has been shown that granulocyte/macrophage colony stimulating factor (GM-CSF) is able to support myeloma cell propagation in cooperation with interleukin (IL)-6, the major growth factor for malignant plasma cells, although the biological mechanisms involved remain unknown. Therefore we investigated (i) the expression levels of the GM-CSF receptor (GM-CSFR) constituents in three malignant plasma cell lines and in native malignant plasma cells, (ii) the ability of the receptor to mediate common signalling pathways regulating proliferation and cell survival in malignant plasma cell lines, and (iii) the effects of GM-CSF on tumour cell biology. The GM-CSFRalpha subunit was detected in the malignant plasma cell lines RPMI-8226, MC/CAR, IM-9 as well as 6/6 native myeloma cell samples derived from the bone marrow of patients with overt disease. Furthermore, GM-CSFR expression was also detected in the CD19+ fraction from 2/3 bone marrow samples and 5/8 peripheral blood samples derived from patients with malignant plasma cell disorders, but not in the CD19+ fraction of peripheral blood from healthy donors. The expressed cytokine receptor alpha-subunit was able to constitute a functional signalling complex with the ubiquitously expressed GM-CSFRbeta subunit, as demonstrated by the fact that GM-CSF induced the p21-ras/mitogen-activated protein kinase (MAPK) signalling cascade in malignant plasma cell lines. Since this signalling cascade plays an essential role in the mediation of both proliferation and cell survival, we investigated the impact of GM-CSF on these two events. Application of GM-CSF led to an increase of DNA-synthesis in MC/CAR, IM-9 and RPMI-8226 cells. Furthermore, it increased longevity of these malignant plasma cell lines by reducing the rates of spontaneous apoptosis. We conclude that (i) the functional GM-CSFR is commonly expressed on malignant plasma cells and that (ii) GM-CSF promotes the clonal expansion of myeloma cells by inhibiting spontaneous apoptosis and promoting DNA synthesis.

Aged↗

PubMed1998

Intervillous blood flow in patients with missed abortion.

AIM: Analysis of the color Doppler features of intervillous flow in cases of missed abortion, and their comparison with the findings in normal pregnancy. METHODS: Transvaginal color and pulsed Doppler was used in the analysis of 38 patients with missed abortion and 40 patients with normal pregnancy. The gestational age ranged from 6 to 11 weeks. Repeated analysis of variance was used to compare the groups. RESULTS: Two types of Doppler signals were detected in the intervillous space: pulsatile and continuous. Impedance in the intervillous space of both groups did not change significantly with the gestational age. For the group with missed abortion, the mean resistance index (RI) was 0.37 +/- 0.03 and pulsatility index (PI) 0.75 +/- 0.07. For the control group, the mean RI was 0.36 +/- 0.02 and PI 0. 72 +/- 0.04. The differences in RI and PI for all gestational age groups and between the two patient groups were not statistically significant. With advancing gestation, continuous, venous-like signal became stronger and randomly dispersed throughout the placenta. Peak flow velocity values obtained from both groups did not change significantly with gestational age, nor between the two groups. Conclusion. The new generation of sensitive Doppler units can detect the intervillous flow as a continuous progressive process at 6-11 weeks of gestation. The vascular resistance in the intervillous space does not change in cases of missed abortion.

Abortion, Missed↗

PubMed1998

Congenital anomalies of the central nervous system at autopsy in Croatia in the period before and after the Chernobyl accident.

In this study, we analyzed the frequency, type and sex distribution of congenital anomalies of the central nervous system (CNS) at autopsy in the period prior to and after the Chernobyl accident in northwest Croatia, one of the areas with the highest exposure to nuclear contamination from Chernobyl. All autopsies in both periods were performed by the same technique, i.e. dissection of the trunk and head, and inspection of the extremities. There were 53 infants with congenital anomalies of the CNS in the period prior to, and 99 in the period after the Chernobyl accident. Our results showed a statistically significant increase in the incidence of CNS anomalies in general (chi 2 = 4,719, p < 0.05, D. F. = 1) and of neural tube defects (chi 2 = 5.380, p < 0.05, D. F. = 1) in the period after the Chernobyl accident. Differences in the incidence of various CNS anomalies, in all types of anomalies, and in sex distribution were not statistically significant. Studies of the association between the Chernobyl accident and congenital anomalies showed no clear changes in the prevalence of anomalies at birth which might have been associated with the accident. This study provided some additional data on the frequency of CNS anomalies in the period after the Chernobyl accident in one of the areas with the highest exposure to the nuclear contamination from Chernobyl. We suggest that the frequency of all anomalies, including CNS, in the period after the Chernobyl accident should be carefully monitored.

Abnormalities, Radiation-Induced↗