Effects of Helicobacter pylori Infection on Ghrelin and Insulin-like Growth Factor 1 Secretion in Children with Idiopathic Short Stature.

BACKGROUND: A diagnosis of "idiopathic short stature" (ISS) in a child means that the cause of the disease has not been established, although there are certainly some unknown factors that contributed to its occurrence. Ghrelin and leptin are important in controlling food intake; ghrelin is also a growth hormone (GH) stimulator. Both enterohormones are produced in the stomach and their secretion may be affected by a Helicobacter pylori (H. pylori) infection. METHODS: Our study included a group of 61 children (53 prepubertal and 8 peripubertal) with ISS, without any gastrointestinal tract symptoms but in whom the histopathological evaluation of stomach tissue was made during gastroscopy to diagnose H. pylori infection. In each child, fasting ghrelin, leptin and IGF-1 concentrations, and GH levels in two stimulation tests were assessed. RESULTS: H. pylori infection was confirmed in 24.6% of the children. Ghrelin and IGF-1 concentrations were significantly lower in H. pylori-positive than H. pylori-negative children (this was more noticeable in prepubertal subgroups), however there was not a discrepancy in regards to GH concentrations in stimulation tests, leptin levels or the nutritional state between groups. CONCLUSIONS: Short children, infected by H. pylori seem to have lower ghrelin and IGF-1 concentrations than children without infection, this may be the reason for a worse growth rate in this subgroup.

The Role of Yersinia enterocolitica O:3 Lipopolysaccharide in Collagen-Induced Arthritis.

Yersinia enterocolitica O:3 is mentioned among the most common arthritogenic pathogens. Bacterial components (including lipopolysaccharide (LPS)) may persist in the joint after eradication of infection. Having an adjuvant activity, LPS may enhance production of anticollagen antibodies, involved in the pathogenesis of rheumatoid arthritis. Furthermore, its ability to activate complement contributes to the inflammation. The aim of this work was to investigate whether Yersinia LPS (coinjected with collagen) is associated with arthritis progression or other pathological effects and to elucidate the mechanism of this association. It was demonstrated that murine mannose-binding lectin C (MBL-C) recognizes the inner core heptoses of the Rd1 chemotype LPS of Yersinia. In addition, the Rd1 LPS activates the MBL-associated serine protease 1 (MASP-1) stronger than the S and Ra chemotype LPS and comparable to Klebsiella pneumoniae O:3 LPS. However, in contrast to the latter, Yersinia Rd1 LPS was associated neither with the adjuvancity nor with the enhancement of pathological changes in animal paws/impairment of motility. On the other hand, it seemed to be more hepatotoxic when compared with the other tested endotoxins, while the enlargement of inguinal lymph nodes and drop in hepatic MBL-C expression (at the mRNA level) were independent of LPS chemotype. Our data did not suggest no greater impact Y. enterocolitica O:3 on the development or severity of arthropathy related to anticollagen antibody-induced arthritis in mice, although its interaction with MBL-C and subsequent complement activation may contribute to some adverse effects.

Interactions of ficolin-3 with ovarian cancer cells.

BACKGROUND: Ficolin-3 is a pattern-recognition molecule with the ability to activate the lectin pathway of complement. It is found in lung, liver and blood, but its physiological role is unclear. We have investigated interaction of recombinant ficolin-3 with malignant cells and tissues. MATERIAL AND METHODS: Cells of various lines of human origin as well as ovarian tissue sections have been studied with the use of flow cytometry and immunohistochemistry. RESULTS: Recombinant (but not serum-derived) ficolin-3 was found to bind strongly to the ovarian cancer cell lines, SKOV-3, OVCAR-3 and ES-2, at concentrations of 2.5 µg/ml and above. Moreover, His-tagged recombinant ficolin-3 (10 µg/ml) preferentially stained ovarian tissue sections from patients with malignant tumours compared with those from patients without. Binding to cell lines was inhibited by EDTA and specific carbohydrate ligands, indicating involvement of the fibrinogen-like domain. Binding was enhanced under mildly acidic conditions and at physiological pH after pre-incubation of cells with mildly acidic buffer. CONCLUSION: Basing on data concerning recombinant protein, it may be suggested that ficolin-3 is involved in immune response in ovarian cancer. However, unidentified serum factor(s) seem(s) to protect cancer cells from recognition by natural or rficolin-3.

Mannose-Binding Lectin (MBL) and MBL-associated serine protease-2 (MASP-2) in women with malignant and benign ovarian tumours.

Mannose-Binding Lectin (MBL) is a serum pattern recognition molecule, able to activate complement in association with MASP proteases. Serum levels of MBL and MASP-2, activities of MBL-MASP complexes, single nucleotide polymorphisms of the MBL2 and MASP2 genes and/or their specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary ovarian cancer (OC) and compared with 197 controls (C), encompassing both patients with benign ovarian tumours (n = 123) and others with no ovarian pathology (n = 74). MBL deficiency-associated genotypes were more common among OC patients than among controls. The O/O group of genotypes was associated with ovarian cancer (OR 3.5, p = 0.02). In A/A homozygotes, MBL concentrations and activities were elevated in the OC group and correlated with C-reactive protein. Moreover, high MBL serum levels were associated with more advanced disease stage. No differences in distribution of the MASP2 +359 A>G (D120G) SNP or MASP-2 serum levels were found between cancer patients and their controls. However, the highest frequency of the A/G (MASP2) and LXA/O or O/O (MBL2) genotypes was found among OC patients with tumours of G1-2 grade (well/moderately differentiated). Furthermore, MBL deficiency-associated genotypes predicted prolonged survival. None of the parameters investigated correlated with CA125 antigen or patients' age. The local expression of MBL2 and MASP2 genes was higher in women with ovarian cancer compared with controls. It is concluded that the expression of MBL and MASP-2 is altered in ovarian cancer, possibly indicating involvement of the lectin pathway of complement activation in the disease.

Ficolin-2 and ficolin-3 in women with malignant and benign ovarian tumours.

Ficolins are serum pattern recognition molecules. They have opsonic properties and are able to activate complement via the lectin pathway. This paper reports investigations concerning ficolin-2 and ficolin-3 in ovarian cancer (OC). Their serum levels, single nucleotide polymorphisms of the corresponding FCN2 and FCN3 genes and specific mRNA expression in ovarian sections were investigated in 128 patients suffering from primary OC and 197 controls operated on for reasons other than malignancies. The latter consisted of two reference groups: those with benign tumours (n = 123) and those with normal ovaries (NO) (n = 74). Serum ficolin-2 and ficolin-3 concentrations were higher among patients with malignant disease when compared with either of the reference groups. A significant correlation between ficolin-2 and ficolin-3 concentrations was found, while no correlations with CA125 antigen or CRP were observed. No differences in the frequency of single nucleotide polymorphisms at sites -64, -4 (promoter), +6359, or +6424 (exon 8) (FCN2 gene) nor in the frame-shift mutation 1637delC (FCN3 gene) were found between investigated groups. In contrast to serum concentrations, the expression of FCN2 gene (reported for the first time in ovarian sections) was significantly lower in women with OC in comparison with patients with NO but not with benign ovarian tumours. In case of FCN3 gene, its expression levels in OC group inversely correlated with serum ficolin-3 and were lower in comparison with controls.

Benign multicystic peritoneal mesothelioma (BMPM) - case report and review of the literature.

Benign multicystic peritoneal mesothelioma (BMPM), also known as multilocular peritoneal inclusion cyst, is a rare tumour that occurs mainly in women at their reproductive age. The aetiology and pathogenesis are controversial. It originates from any abdominal peritoneal or pleural surface. The biological behaviour of BMPM is usually clinically benign. Here we present a case report of BMPM from our department with a review of the literature.

[Comparative analysis of abnormal Pap smear and the results of histopathological examination of specimens from the cervix of the programme in-depth diagnosis cervical cancer conducted at the of Operational Gynecology Department ICZMP in Lodz]. / Analiza porównawcza nieprawidlowych wyników badania cytologicznego z wynikami badania histopatologicznego wycinków z szyjki macicy w ramach Programu Poglebionej Diagnostyki Raka Szyjki Macicy realizowanego w Klinice Ginekologii Operacyjnej ICZMP w Lodzi.

INTRODUCTION: Cervical Cancer Screening Program has been operational in Poland for over four years. Colposcopy and guided biopsy methods constitute an essential part of population-based screening, enable stating right diagnosis and planning treatment procedures. AIM: The aim of the following study was to analyse the diagnostic acuity of cyto- and histopathological examination. RESULTS: We examined 510 patients with the following result of cytological smear: ASCUS--265 women (51.96%), LSIL--167 cases (35.75%), HSIL--78 women (15.29%). Complete agreement between cytological smear and guided biopsy histopathology was observed among 81.13% cases of ASCUS, in 88.02% of women with LSIL and in 76.92% cases with the diagnosis of HSIL. As with cytology-biopsy comparisons, discordant cases were significantly more frequent in the group with stated HSIL than among patients with the diagnosis of ASCUS or LSIL (p<0.001). CONCLUSIONS: 1. High cyto-histopathological accordance (82%) has been obtained, what is comparable with the data in literature. 2. The highest cyto- histopathological compatibility was obtained in the group of patients with LSIL--over 88%, and the lowest in the group of patients with HSIL--less than 77%. 3. Failure to confirm the histopathological diagnosis of cytological HSIL requires further molecular and morphological evaluation.

[Intensification of Helicobacter pylori colonization and serological markers of Helicobacter pylori infection and cytotoxicity in blood]. / Nasilenie kolonizacji bakterii Helicobacter pylori, a serologiczne markery zakazenia i cytotoksycznosci Helicobacter pylori we krwi.

UNLABELLED: Colonization of H. pylori bacteria on the surface of gastric epithelium is the first stage of infection in alimentary tract. Despite the local cell-mediated reaction, in the majority of patients there does not come to the elimination of bacteria: there develops an acute and then chronic inflammatory process. B lymphocytes begin the production of all classes of specific antibodies against H. pylori proteins presented to them. The number of anti-H. pylori antibodies increases both in gastric mucosa and in peripheral blood. According to some researchers the intensification of colonization influences the severity of inflammatory process. AIM OF THE STUDY: To assess whether on the basis of examination of anti-H. pylori and anti-CagA H. pylori surface antibodies in blood it may be concluded that there is an intensification of H. pylori colonization in the stomach. MATERIAL AND METHODS: The study comprised 154 children aged 5-18 years (mean 13.6 +/- 3.6 years) with alimentary tract ailments: 99 children with active H. pylori infection (Hp+) and 55 children without current H. pylori infection (Hp_). In blood there were examined anti-H. pylori surface antigens IgG class (with ELISA), anti-CagA H. pylori antibodies IgG class (with ELISA), and in gastric mucosa specimens the intensification of H. pylori colonization was tested with the use of semi quantitative method. Statistic analyses were performed. RESULTS: Anti-H. pylori antibodies IgG class were present in the serum of 88.3% of the examined children, including in 96% of children from Hp+ group and 75% from Hp_ group. Anti-CagA H. pylori specific antibodies were found in 56.7% of children from Hp+ group and were not detected in Hp_ children. Spiral H. pylori forms were more frequently revealed in the prepyloric part of the stomach (of medium or small intensification) than in the corpus (of small intensification) (77.8% vs. 56.5%, p < 0.001). Positive correlation was demonstrated between the number of bacteria in tissue and index value of antibodies against anti-H. pylori surface antigens in serum (R = 0.45, p < 0.001) (particularly in the prepyloric part of the stomach) and high positive correlation was shown between density of spiral H. pylori bacteria in gastric mucosa bioptates and the occurrence of anti-CagA antibodies in serum (R = 0.59, p < 0.001) and index value of anti-CagA H. pylori antibodies in serum (R = 0.58, p < 0.001). CONCLUSIONS: High concentrations of anti- H. pylori IgG class surface antibodies and occurrence of anti-CagA antibodies in blood correlate with high intensification of H. pylori colonization in the prepyloric part of the stomach.

[Alport syndrome in 23-year-old woman]. / Zespól Alporta u 23-letniej kobiety.

We report a case of Alport syndrome in a 23-year-old woman. Early-onset microscopic hematuria, nephrotic syndrome, arterial hypertension and the presence of extrarenal symptoms, e.g. hearing loss are risk factors of disease progression towards renal failure in the patient. This case report emphasizes the importance of electron microscopic studies in the diagnosis of hereditary nephropathies.

Glomerular basement membrane thinning in children: a morphometric assessment.

OBJECTIVE: To develop our own procedures, allowing for a quick evaluation of glomerular basement membrane (GBM) thickness and to present a statistical classification of thin basement membrane disease (TBMD), minimal change disease (MCD), and IgA nephropathy (IgAN) cases. STUDY DESIGN: Measurements were carried out with the aid of the original software for semiautomatic image analysis on biopsies from 31 children with TBMD, 51 with MCD, and 10 with IgAN. RESULTS: The strongest statistically significant dependence between GBM thickness and age was observed in children with MCD below 5 years of age. There was no significant dependence between GBM thickness and age among patients with TBMD. The values of all analyzed parameters characterizing GBM thickness distribution in children with TBMD were significantly lower than those in patients with MCD and IgAN. A slight, statistically significant increase of some parameters was noted in children with IgAN in contrast to patients with MCD. The multivariate logistic regression model with three independent variables--quartile 1, quartile 3, and percentile 30--proved to be the most appropriate in differentiating between patients with TBMD and children with MCD or IgAN. The model allowed for correctly classifying 96.8% of patients with TBMD (30 of 31 children) and 98.4% patients from the MCD and IgAN groups (60 of 61 children). We failed to construct a similarly appropriate model for differentiating between patients with MCD and IgAN. CONCLUSION: The introduction of morphometric and statistical methods to routine nephropathologic diagnostics represents true progress in very precise and quick assessment of GBM thickness.

Inter-observer variability in histopathological assessment of liver biopsies taken in a pediatric open label therapeutic program for chronic HBV infection treatment.

AIM: To our knowledge, the inter-observer variability of the liver biopsy findings in HBV-infected children have not been studied as yet. Hence, we aimed to compare different pathologist's assessment of grading and staging in liver biopsies obtained from children prior to interferon treatment. METHODS: We collected 920 biopsies from 11 medical centers. The biopsies were independently reviewed by 6 pathologists from academic centers who assessed Batts-Ludwig score for grading and staging. Satisfactory agreement among observers was defined as at least 60% of observers having the same opinion. Satisfactory dispersion between maximal and minimal score for the same biopsy specimen was defined as a maximum 1 point. RESULTS: Satisfactory inter-observer agreement for grading was obtained in 51.6% and for staging in 75.7% of biopsies. Satisfactory dispersion for grading scores was observed in 44.5% and for staging in 72.7% of cases. CONCLUSION: Our study demonstrates that: (1) pathologists differ in their assessment of grading and staging of liver biopsies; (2) inter-observer variability for staging is lower than that for grading; and (3) regardless of the inter-observer variability of assessments, the majority of children with chronic HBV infection have mild to moderate inflammation and mild to moderate fibrosis.

[The spectrum of congenital malformations of the urinary tract in fetuses and newborns in autopsies in 1989-2002]. / Wystepowanie wad ukladu moczowego plodów i noworodków w materiale autopsyjnym w latach 1989-2002.

The retrospective analysis of own autopsy findings of 831 fetuses and newborns with different forms of congenital malformations were carried out. In 172 cases (20.7%) urinary tract abnormalities were revealed. Isolated malformations represented 43.6% (75 cases) and 56.4% (97 cases) constituted one component of complex multisystem anomalies. Obstructive uropathies with different renal changes represented 54.7% of the isolated malformations, renal agenesis - 28%, autosomal recessive or dominant polycystic renal diseases - 16% and renal hypoplasia 1.3%. Obstructive uropathies were also most prevalent among the multisystem abnormalities (45.4%), while agenesis represented 34% of cases, horseshoe kidney - 12.4%, autosomal polycystic kidney diseases 4.1%, and renal hypoplasia 4.1%. Congenital abnormalities of urinary tract (especially the obstructive uropathies and agenesis) were more common in male fetuses and newborns. A highly frequent coexistence of urinary system congenital abnormalities and malformations of digestive tract, circulatory system and central nervous system were observed.

[Acardiac fetus--morphological and clinical aspects]. / Morfologiczne i kliniczne aspekty plodów bezsercowych.

The authors described 6 cases of serious complication of the multiple pregnancies with twin-to-twin transfusion syndrome (TTTS) sub form twin reverse arterial perfusion (TRAP) with development of acardiac fetus. It was established that this anomaly is an extremely rare complication of multiple pregnancies and very uncommon congenital malformation disclosed in fetuses and newborns. Acardiac "recipient" fetuses may have different morphological forms and often their birth weight is higher than that of the "donor" fetuses. The latter represent morphologic features of circulatory overload due to the necessity of supplying blood to the amorphous acardiac fetus. They are usually born preterm with circulatory insufficiency, intrauterine hypoxia and with developmental anomalies. Survival of one of the "donor" fetus implies the necessity of early diagnosis to detect pregnancy pathology, possible intrauterine intervention and monitoring of the healthy twin.

[Cervical glandular intraepithelial neoplasia topography and the risk of conisation]. / Przedinwazyjne rozrosty gruczolowe w szyjce macicy: topografia zmian i zagrozenia dla konizacji.

OBJECTIVES: The frequency of endocervical adenocarcinoma is increasing in comparison with squamous cell carcinoma and it presents a very difficult diagnostic and therapeutic problem. DESIGN: The aim of this study was: 1) Evaluation of topography of the cervical glandular intraepithelial neoplasia (CGIN) 2) An analysis of the Human Papillomavirus (HPV) infection rate in samples. MATERIALS AND METHODS: 360 amputated uterine cervix samples with histologically-proven diagnosis of cervical intraepithelial neoplasia (CIN-3) were evaluated. The coexistence of pre-invasive lesions in squamous epithelium and endocervical columnar cell were investigated. Moreover CGIN topography and retrospective histopathological analysis were determined. A polymerase chain reaction (PCR) was performed using commercially available PCR Human Papillomavirus Typing Set to detect HPV infection. RESULTS: Among 360 positive cervical intraepithelial glandular neoplasia samples (CIN-3) 71 (19.7%) showed coexisting glandular lesions (CGIN-1, 2, 3). The lesions in endocervical glandular cells of CIGN-type were distributed from the distance up to 14 mm from the surface of cervix. Most of them were located no deeper than 1 mm from the surface of canal epithelium. HPV DNA was found in more than 90 preneoplastic glandular proliferations. The frequency of oncogenic HPV-16 and 18 presence was higher than non-oncogenic HPV. CONCLUSIONS: 1. CIN-3 is associated in about 20% with cervical glandular intraepithelial neoplasia (CGIN). 2. Topography of CGIN is important in planning the management. 3. Most of CIGN are associated with HPV infection.

Morphological and immunological features of liver inflammatory infiltrate in children with chronic hepatitis C.

UNLABELLED: The aim of the study was to assess the correlation between morphological and immunological features of lesions in the liver in children with chronic hepatitis C. In the study 11 children with chronic hepatitis C were enrolled. Histopathological and immunomorphological investigations included antigen marking CD45, CD45RA, CD45RO, CD20, CD3, CD8 in liver biopsy specimens. The immunomorphological assessment of the inflammatory infiltrate cells showed the presence of CD45 antigen on the vast majority of leukocytes in the portal tracts and in the lobular parenchyma in all the studied children. One fourth of the inflammatory cells were characterised by CD20 phenotype, 1/2--by CD3 phenotype, 1/3--by CD8 phenotype, 1/3--by CD45RA phenotype and 2/3--by CD45RO phenotype. CONCLUSIONS: T and B lymphocytes were predominant in hepatic inflammatory infiltrates (T lymphocytes are twice as numerous as B lymphocytes). Among T lymphocytes, cytotoxic and suppressor cells were prevailing. Most T lymphocytes were characterized by CD45RO phenotype, which shows their activation. A positive correlation between most lymphoid cell markers, staging and grading suggests the role of these cells in liver injury.

[Intrahepatic and peripheral blood NK cells in patients with chronic hepatitis C]. / Analiza wspólzaleznosci pomiedzy komórkami nk watroby i krwi obwodowej u dzieci z przewleklym zapaleniem watroby typu c.

UNLABELLED: The aim of this study was to evaluate the correlation between NK (natural killers) cells in an inflammatory infiltration of the liver and in peripheral blood in children with chronic hepatitis type C. MATERIAL AND METHODS: The study comprised 25 children with chronic hepatitis type C. The control group comprised 10 children with no liver disease in past medical history and normal activity of aminotransferases. In the study group, liver biopsy specimens were evaluated by histopathology and immunomorphology - the presence of NK cells present in the inflammatory infiltrate was determined. In all children the percentage and absolute count of NK cells in peripheral blood was evaluated by flow cytometry, as well as the activity of NK cells in relation to leukaemic cells of erythroleukemia K-562 without stimulation and after the stimulation with IL-2 (in vitro). RESULTS: In the studied group of children NK cells constituted 6.07 +/- 3.92 % of cells present in liver infiltrate. In peripheral blood NK cells constituted 11.68 +/- 6.73 % of white blood cells, and their absolute number was 241.08 +/- 128.56 /ml. The cytotoxic activity of NK cells in dilution E:T 25:1 was - 91.8 +/- 1.07 % and in dilution E:T 12.5:1 - 6.72 +/- 3.68 %. After stimulation with IL-2 it was 92.8 +/-1.01 % and 7.58 +/- 3.95 %, respectively. The number of NK cells in peripheral blood and cytotoxic activity of NK cells in the studied group did not differ from that of the control group. There was a positive correlation between the percentage of NK cells in the liver infiltrate and the absolute number of NK cells in the peripheral blood and between percentage of NK cells in the inflammatory infiltrate and cytotoxic activity of NK cells in peripheral blood, stimulated and non-stimulated with IL-2 in proportion E:T 12.5:1. CONCLUSIONS: Positive correlation between the number of NK cells in peripheral blood and liver infiltrate suggests the possibility of evaluating NK cells involvement in the pathogenesis of chronic hepatitis type C in children on the basis of peripheral blood tests.