Herman Haller

Characteristics of Perforin Expressing Lymphocytes Within the First Trimester Decidua of Human Pregnancy

PROBLEM: The number of perforin (P)‐positive cells in decidua of pregnancy is larger than that observed in any other pathological condition. The aim was to investigate the distribution and the phenotype of P+ cells.

Transvaginal sonography and hysteroscopy in women with postmenopausal bleeding.

Objective: To make a prospective comparison between endometrial thickness determined by transvaginal sonography (TVS) and hysteroscopic findings in women with postmenopausal bleeding with histologic findings obtained by dilatation and curettage (D&C). Methods: Eighty‐one patients who had not received hormonal replacement therapy were scanned by transvaginal probe, and double‐layer endometrial thickness was measured 1 day before hysteroscopy and D&C. Results: The histologic diagnosis was atrophy in 12 cases, irregular proliferative changes in 21, endometrial polyps in 16, hyperplasia in 16 and endometrial carcinoma in 16. TVS detected 46 of 48 pathologic conditions, including all cases of endometrial carcinoma if the endometrial thickness (both layers) was ≥ 5 mm (sensitivity 95.8%, specificity 45.5%). Hysteroscopy also detected the endometrial pathology in 46 of 48 cases but with a higher specificity (sensitivity 95.3%, specificity 93.9%). Conclusion: TVS and hysteroscopy are complementary diagnostic methods and could be accurately used to discriminate between normal and pathologic conditions in patients with postmenopausal bleeding.

An immunohistochemical study of leucocytes in human endometrium, first and third trimester basal decidua

An immunohistochemical quantitative study of leucocyte subpopulations on fresh human endometrium and on biopsy specimens of first and third trimester basal decidua in normal (uncomplicated) pregnancies was performed. The most prominent population in endometrial and decidual stroma of basal decidua are macrophages. B cells as well as gamma/delta T cell receptor positive cells were found occasionally, scattered throughout the endometrial/decidual stroma. CD3+ cells were present in a relatively small number in the endometrium as well as in the first trimester basal decidua, but their number was elevated (doubled) in the third trimester of pregnancy. CD2+ cells showed a slight increase in first trimester basal decidua when compared with both endometrium and third trimester basal decidua. Cells with positive NKH-1 marker (CD56+) showed a significant increase in the first trimester, while in the third trimester their number diminished drastically. CD56:CD3 cell ratio increased to more than five times in first trimester basal decidua, while in the third trimester basal decidua decreased drastically. The mentioned increase of CD56+ cells in the first trimester and that of CD3+ cells at term suggests that these cells could have some specific function(s). However, it still has to be established whether the described quantitative changes of decidual leucocytes in basal decidua during pregnancy are of any importance for the mechanism(s) for the fetal allograft protection.

Decidual natural killer cell tuning by autologous dendritic cells.

Problem  Dendritic cells (DC)/natural killer (NK) cells interactions in the deciduas of early human pregnancies were analyzed in vitro.

ORIGINAL ARTICLE: Decidual Natural Killer Cell Tuning by Autologous Dendritic Cells

Problem  Dendritic cells (DC)/natural killer (NK) cells interactions in the deciduas of early human pregnancies were analyzed in vitro.

Decidual-trophoblast interactions: decidual lymphoid cell function in normal, anembryonic, missed abortion and ectopic human pregnancy

This study was designed to investigate the consequences of decidua-trophoblast interactions on the phenotype, spontaneous and induced proliferation and immunoregulatory potential of decidual leukocytes in normal pregnancies (NP), anembryonic pregnancies (AP), missed abortions (MA) and ectopic pregnancies (EP). Spontaneous proliferation of decidual non-adherent cells (NAD) from pregnancies with viable trophoblast inside the uterus is significantly higher than proliferation of peripheral blood lymphocytes (PBL) from the same groups (P < 0.001 for NP; P < 0.05 for AP). Spontaneous proliferation of decidual NAD cells from NP was higher (P < 0.001) when compared with AP and EP. The induced (PHA and Con A) responses of PBL from women with normal and pathological pregnancies were significantly higher than that of decidual NAD cells (P < 0.001). Higher proliferation of NAD decidual cells was obtained when Con A-stimulated NP were compared with MA and EP (P < 0.01). The interaction of viable trophoblast with intrauterine decidua appears to be a prerequisite for the activation of NAD suppressor cells, since NAD cells from MA produced stimulation instead of suppression, and NAD cells from EP had no suppressive effect. On the contrary, both NAD and adherent (AD) decidual leukocytes from NP and AP produced very strong suppression of PHA or alloantigen-induced PBL proliferation. The contact between trophoblast and AD decidual leukocytes is not necessary for their suppressive function, since even higher suppression is obtained with the cells from ectopic pregnancies.

Phenotype of NK cells and cytotoxic/apoptotic mediators expression in ectopic pregnancy

Citation Laskarin G, Redzovic A, Vukelic P, Veljkovic D, Gulic T, Haller H, Rukavina D. Phenotype of NK cells and cytotoxic/apoptotic mediators expression in ectopic pregnancy. Am J Reprod Immunol 2010

Pregnancy Loss and Maternal Methemoglobin Levels: An Indirect Explanation of the Association of Environmental Toxics and Their Adverse Effects on the Mother and the Fetus

The aim of this epidemiologic study was to point out a relationship between the exposure to products of coal combustion, and complications in pregnancy where one third of causes of stillbirth are still unknown. In the town of Labin (Croatia) a coal-powered thermoelectric power plant is the single major air polluter. We compared the records of miscarriages, premature births and stillbirths in two periods: the control and the exposure period. Data on reproductive loss was based on the records of pregnant women visiting for regular monthly pregnancy checkups. At the time of the epidemiological prospective study, 260 women (n = 138 in the clean period and n = 122 in the dirty period) were considered representative. The data were processed using Chi square and correlation tests. The frequencies of miscarriages and stillbirths were significantly lower in the control than in the exposure period (p < 0.05). Methemoglobinemia and stillbirths recorded over the “exposure” period are significantly higher than in the “control” period (p = 0.0205). The level of methemoglobin in the bloodstream is an worthy biomarker, predictor and precursor of environmental toxics’ adverse effects on the mother and fetus, and can indirectly explain the unrecognized level of fetal methemoglobin. Methemoglobin and heme, having prooxidant properties, also cause the early and late endothelial dysfunction of vital organs. Despite our retrospective epidemiological study findings, we emphasize that the rate of reproductive loss represents a hypothetical risk, which needs to be confirmed with further fetal clinical and anatomopatholgical researches about the effects of methemoglobin catabolism products on the fetal CNS.

First Trimester Pregnancy Decidual Natural Killer Cells Contain and Spontaneously Release High Quantities of Granulysin

Citation Veljkovic Vujaklija D, Gulic T, Sucic S, Nagata K, Ogawa K, Laskarin G, Saito S, Haller H, Rukavina D. First trimester pregnancy decidual natural killer cells contain and spontaneously release high quantities of granulysin. Am J Reprod Immunol 2011; 66: 363–372

Fetal transverse cerebellar diameter/abdominal circumference ratio in assessing fetal size

Objective: To test the usefulness of the fetal transverse cerebellar diameter/abdominal circumference (TCD/AC) ratio in predicting known small‐for‐gestational‐age (SGA) infants. Method: The relationship between fetal TCD and AC throughout the second half of pregnancy was investigated in 635 well‐dated, normal pregnancies and examined with regard to gestational age and infant birth weight percentiles. Results: One hundred eighteen (19%) fetuses were excluded due to inadequate visualization of the fetal cerebellum. A strong correlation was noted between gestational age determined by the last menstrual period and both fetal TCD (r2 = 0.91338) and AC (r2 = 0.89361) in fetuses with birth weights between the 10th and 90th percentiles (n = 407; mean 14.4, S.D. 1.2). Although the TCD/AC ratio showed a poor correlation with gestational age (r2 = 0.15788), a slight increase was noted during gestation. A TCD/AC ratio greater than 15.5 was present in 80% of SGA infants when measurements were performed within 1 week of delivery. Conclusion: Fetal TCD/AC ratio as a gestational age‐independent method could improve diagnostic sensitivity and specificity in the early detection of fetal growth abnormalities.