Early prenatal detection of a fast-growing fetal epignathus.

Epignathus is a rare congenital orofacial teratoma. We present a case of a fast-growing tumor, where early prenatal diagnosis was made and where fetopathological examination revealed the reason of the remarkable ultrasonographic signs and underlined the expected poor prognosis. Ultrasonographic examination at 18 weeks' gestation showed that there was a growing tumor protruding from the fetus's mouth. The fetal stomach could not be seen and extreme polyhydramnios was also detected. After counseling, the couple opted for a termination of pregnancy. Fetopathological examination showed that the tumorosus mass was not only protruding from the mouth, but also inexplicably grew downwards, was connected to the hard palate and the periosteum of the vertebral corpus, making an airway and esophageal obstruction, causing the ultrasonographic findings. Postnatal treatment and surgical removal of this tumor seemed to be impossible. In case of an early detection of a fast-growing fetal epignathus, pregnancy termination should be considered.

Retrospective analysis of low-risk differentiated thyroid tumours: is lobectomy the adequate approach? / Kis rizikójú differenciált pajzsmirigydaganatok retrospektív analízise: lobectomia a megfelelo választás?

Introduction: According to the recommendation of the American Thyroid Association 2015 guideline, the treatment of 1-4 cm (T1b-2) low-risk differentiated thyroid cancer (DTC) is lobectomy without radioiodine therapy. Objective: Retrospective analysis of multifocality in surgical and histological data of T1-2 patients living on moderate iodine intake. Methods: Analysis of the pathological characterisation of 81 low-risk (T1-2) DTC patients who underwent total thy-roidectomy. Patients were treated at Flor Ferenc Hospital, Kistarcsa, Hungary, between 2013 and 2019. Results: 64 patients had T1, while 17 patients had T2 status. 65/81 (80.2%) patients had papillary, and 16/81 (19.8%) had follicular subtype. Lymph node metastasis was detected up to 18.4% in papillary and 18% in follicular patients. Multifocal tumours were detected in 25% (16/64) of T1 patients, of these 10.9% (7/64) was unilateral and 14.1% (9/64) was bilateral. Multifocal tumours were detected in 11.7% (2/17) of T2 patients; both were bilateral. Distribution of T1-2 bilateral multifocal patients (11/81; 13.5%) was n = 3 T1a-, n = 6 T1b and n = 2 T2 stadium, from these 10 patients received radioiodine treatment. The sizes of contralateral tumours were <5 mm in 9 patients, and >5 mm in 2 patients. Conclusions: Due to the frequent (13.5%) bilateral multifocality in T1-2 DTC patients, we suggest total thyroidec-tomy instead of lobectomy. After lobectomy, the follow-up of the contralateral tumours is almost impossible by ul-trasonography due to the small tumour size (on average 2.8 mm) and frequently detected benign nodules; therefore the multifocality might remain undetected, which can distort the plan for adjuvant treatment.

[Pentalogy of Cantrell: six new cases]. / Cantrell-pentalógia: a praenatalis felismerés lehetoségei hat saját eset kapcsán.

UNLABELLED: Cantrell's pentalogy is a rare multiple malformation syndrome consisting of supraumbilical abdominal wall defect, sternal defect, pericardial defect, anterior diaphragmatic defect and heart malformation. AIMS AND METHODS: Prenatal ultrasound findings and malformations described during autopsy of the Cantrell's pentalogy cases diagnosed between January 1991 and June 2009 in our institute were reviewed. A literature research was conducted to analyze the prevalence and prenatal detection rate of the five previously described malformations and ectopia cordis in the Cantrell's pentalogy cases. RESULTS: Six cases of Cantrell's pentalogy were diagnosed during the study period in our department. Sonography detected multiple malformations in 3 cases, and isolated malformation in 3 cases. Analyzing the data of 49 Cantrell's pentalogy cases altogether showed that, beside abdominal wall defect and ectopia cordis which had the highest prenatal detection rate (83% and 91% with a prevalence of 94% and 69%, respectively), sternal defect and anterior diaphragmatic hernia were also present in a large number of the cases (80% and 73% respectively). CONCLUSION: Sonographic identification of the sternal defect or diaphragmatic hernia may help to differentiate Cantrell's pentalogy from malformations part of the syndrome but occurring as isolated defects.

Prenatally diagnosed fetal brain injuries with known antenatal etiologies.

Periventricular leukomalacia of pre- or postnatal onset is responsible for severe neurological and intellectual impairment and cerebral palsy later in life. The etiology is multifactorial, involving hypoxic-ischemic insults of various origin. The disorder is characterized by multiple necrotic foci of the white matter found most frequently adjacent to the lateral ventricles. In the past, intrapartum factors were thought to be the major cause of neonatal brain damage, but recent investigations highlighted the role of antenatal risk factors. We present 4 cases of antenatally diagnosed brain injury with known and unusual etiology.

Effect of hormone replacement therapy on postmenopausal endometrial bleeding.

The aim of the study was to determine the effect of postmenopausal hormone replacement therapy (HRT) (treatment using estrogen only and sequential and continuous combined estrogen-progestogen treatment) on endometrial bleeding and histological changes of the endometrium. In a six-year period (2000-2005), 5893 patients were given care and the incidence of postmenopausal uterine bleeding was detected in groups of patients having and not having received hormonal treatment at the Menopause Outpatient Unit of the authors' department. In the case of bleeding, fractioned abrasion was performed and the samples were analyzed histologically. Among the postmenopausal patients who had not been given hormonal treatment, the incidence of bleeding episodes was significantly higher as among those having received hormonal treatment. In the samples, findings of proliferative endometrium occurred significantly more often in case of non-treated patients and those treated with sequential combined hormone therapy compared to patients receiving continuous combined hormone therapy. Although it was statistically not significant, hyperplasia simplex and complex together showed a tendency of reduced incidence in patients medicated by continuous combined treatment. These findings suggest that continuous combined hormonal treatment started at the right time (even before the menopause) may reduce the chances of the development of hyperplasia. A significantly higher incidence of hyperplasia was noted in patients using estrogen treatment only. It is possible that unopposed estrogen treatment further engraves an already diagnosed endometrial hyperplasia. In the group having received hormonal treatment, no complex hyperplasia accompanied by atypia occurred, only hyperplasia simplex was diagnosed in these cases. As a result of continuous reliance on combined preparations, the endometrium had become atrophied, therefore the chance of hyperplasia-related changes and of bleeding as a side effect decreased significantly. According to the authors' experience, hormonal treatment does not pose a risk to the development of endometrial carcinoma; on the contrary, continuous combined preparations appear to reduce the risk of hyperplasia and, indirectly, the chances of the development of adenocarcinoma.

Quality control of prenatal sonography in detecting trisomy 18. The value of perinatal autopsy.

AIMS: This study was designed to compare the prenatal ultrasound findings and postmortem pathologic findings of fetuses with trisomy 18. STUDY DESIGN: Of 22,150 fetal chromosome analyses, 70 fetuses with trisomy 18 were diagnosed between 1990 and 2004. Sonographic and perinatal autopsy findings were compared by organ system and their correlation was assigned to 1 of 3 categories. RESULTS: There were 164 separate major structural abnormalities found on autopsy. Of them, sonography detected 72 (43.9%). Among major defects the agreement was more than 75% of all abnormalities of these systems: central nervous system (80%), abdominal abnormalities (87.5%) and cystic hygroma (100%). Whereas, the sensitivity of sonography was lower in these organ systems: cardiac system (66.6%), facial abnormalities (26.3%), urinary system (27.3%) and extremities (8.7%). The rate of additional findings at autopsy was 56.1% and involved mainly 2 organ systems: face (including ear) and extremities (including hands and feet). Some ultrasound findings (n=15) were not confirmed at autopsy in our series. CONCLUSIONS: This study confirms that perinatal autopsy provides additional information in many fetuses with trisomy 18. Besides obstetricians, pediatricians and geneticists, specialized perinatal pathologists have an important role in the multidisciplinary management of prenatally diagnosed fetal malformations. In addition, examining the correlation between sonography and pathologic findings may indicate potential markers for sonographic screening of trisomy 18.

[Analysis of the dopamine D4 receptor gene variants in attention deficit hyperactivity disorder]. / A dopamin D4-es receptor génvariánsok vizsgálata figyelemhiányos hiperaktivitási zavarban.

The human dopamine D4 receptor (DRD4) gene has been extensively studied as a candidate gene for attention deficit hyperactivity disorder (ADHD). Both the 5' regulatory region and the coding sequence contain a number of polymorphisms. The most widely investigated polymorphism of the DRD4 gene is the 48 bp VNTR (Variable Number of Tandem Repeats) in the third exon. The promoter variants have received particular attention in the past few years due to their possible role in the regulation of gene expression. In this study we describe an association analysis of the 120 bp duplication and three sequence variations (SNPs, Single Nucleotide Polymorphism; -616 C/G, -615 A/G, -521 C/T) in the 5' region of the DRD4 gene is presented among children with ADHD. In case-control approach, the 1-repeat form of the 120 bp duplication had a significantly higher frequency among ADHD children than controls, both in allele-(p=0.047), and genotype (p=0.019) distributions. There was no significant difference between the ADHD and control groups in the allele or genotype frequencies of the investigated SNPs. The transcriptional effect of the 120 bp duplication was analysed in luciferase reporter system. The different 120 bp duplication alleles (1-repeat, 2-repeat and the newly identified 4-repeat allele) was found to have an effect on transcriptional activity of the DRD4 gene in both neuroblastoma and retinoblastoma cell lines in a dose-dependent manner. The higher was the repeat number of the 120 bp sequence in the promoter, the stronger was the decrease of the gene transcription (1-repeat > 2-repeat > 4-repeat; p<0.01). These results of association and functional analyses suggest that the 1-repeat form of the 120 bp duplication might be a risk factor of ADHD.

[The effect of postmenopausal hormone replacement therapy on endometrial bleeding]. / A postmenopausalis hormonpótló kezelés hatása a változókorban jelentkezo vérzészavarra.

OBJECTIVE: The aim of this study was to determine the effect of postmenopausal hormone replacement therapy (exclusively oestrogen or sequential/continuous combined oestrogen-progestogen treatment) on endometrial bleeding, including the histological alteration of the endometrium. PATIENTS: From January 2000 to December 2005, 5893 women were treated by the authors in the menopause unit of their department. They examined the frequency of menopausal bleeding in treated and control groups. In case of bleeding, dilatation and fractional curettage was always carried out and the tissues were histologically evaluated. RESULTS: In menopausal patients who did not obtain hormone replacement therapy, bleeding occurred twice as frequently as in the treated group. Proliferating or hyperplastic endometrium was observed mainly among the treated patients, suggesting that in due time, even before the age of menopause, hormonal treatment might decrease hyperplasia and indirectly the chance of occurrence of adenocarcinoma. Hyperplasia was found more frequently in patients obtaining only oestrogen. According to the authors' view, unbalanced oestrogen treatment might further aggravate the existing hyperplasia of the endometrium. In the group treated with hormonal therapy, only simplex hyperplasia was observed. No case of complex hyperplasia with atypia was found among these patients. In the majority of patients on continuous balanced hormonal therapy, the myometrium underwent atrophy and the frequency of hyperplasia, including the chance of bleeding, mostly decreased. Endometrial polyps most frequently were found under hormonal therapy, but no acceptable explanation can be provided. The rate of cervical polyps was also higher in this group. CONCLUSIONS: According to the observations of the authors, hormone replacement therapy does not increase the risk of endometrial carcinoma. Combined preparations decrease the frequency of hyperplasia and consequently the chance of occurrence of adenocarcinoma.

[Radical vulvectomy to treat severe vulvar acne inversa]. / Szeméremtesten megjelenõ acne inversa sikeres kezelése radikális vulvectomia útján.

UNLABELLED: A rare case, when radical vulvectomy had to be done to treat a benign skin disorder is presented. PATIENT AND METHOD: A 56-year-old white woman suffered from severe vulvar acne inversa. The systemic treatments, the incisions and drainages were not successful. The only solution was the radical excision of the seriously damaged vulva, with a satisfactory cosmetic and functional result. The pathology, the diagnosis and the treatment of the disease are also discussed. CONCLUSION: The authors put emphasis on the importance of the interdisciplinary collaboration.

[Double kidney transplantation--a method to increase the donor pool]. / Kettos vese átiltetés--egy lehetoség a transzplantációk számának növelésére.

The patients number on the transplant waiting lists are continuously increasing. The number of donors and transplantations can not reach this acceleration. To increase the number of organs we can use living donor organs or carefully selected extended criteria organs. To achieve appropriate function with marginal donor kidneys we need to transplant both kidneys into the same recipient. At the Transplant Division of University of Texas during a two years period we performed 5 double kidney transplantations with organs refused by the local transplant services. We placed both kidneys to the same side, retroperitoneally. The recipients mean age was 44.4 years and two of them belonged to the immunological risk ethnic group. After the transplantation all kidneys showed immediate function. During the patients mean hospital stay (6.25 days) the serum creatinine level decreased from 1000 micromol/l to 350 micromol/l. The Glomerular Filtration Rate (GFR) increased from 7 ml/min to 41 ml/min. Two patients suffered acute rejection which influenced their kidney function. During our two year follow up all patients avoided haemodyalsis. Double kidney transplantation is an acceptable solution for expanding the donor pool. After consistent and cautious selection previously rejected kidneys can be used.

No direct effect of the -521 C/T polymorphism in the human dopamine D4 receptor gene promoter on transcriptional activity.

BACKGROUND: The human dopamine D4 receptor (DRD4) gene has been studied extensively as a candidate gene for certain psychological traits and several behavioural and psychiatric disorders. Both the 5' regulatory region and the coding sequence contain a number of polymorphisms. The promoter variants have received particular attention in the past few years due to their possible role in the regulation of gene transcription. Previously, the -521C/T SNP was shown to influence promoter activity. The aim of this study is to perform an in-depth analysis of this effect in the context of various neural cell lines. RESULTS: Endogenous mRNA expression of the DRD4 gene was demonstrated in two neuroblastoma (SK-N-F1, IMR32) and one retinoblastoma cell line (Y79) by RT-PCR. In addition, very low DRD4 mRNA levels were also detected in HeLa cells. The transcriptional activity of a series of 5' promoter deletion mutants was determined by transient transfection of luciferase reporter constructs. The activity profile of these promoter fragments was similar in each of the cell lines tested. The highest luciferase reporter activity was obtained with a construct containing promoter sequences between nucleotides -668 to -389, while a putative silencer region was localised spanning from nucleotide -1571 to -800. Surprisingly, the -521 C/T polymorphism had no significant effect on transcriptional activity of the reporter construct with the highest activity (-668 to -389) in any of the three cell lines tested. CONCLUSION: Our results do not confirm previous data assigning different transcriptional activities to the -521 C/T alleles of the human DRD4 promoter. Furthermore, these findings highlight the need for further characterization of the 5' regulatory region of the DRD4 gene and identification of additional functional promoter polymorphic sites, especially in the context of haplotype.

[Wertheim-operation: 5-year survival of 501 consecutive patients with cervical cancer]. / Wertheim-mutét: 501 operált méhnyakrákos beteg ötéves túlélési adatai.

OBJECTIVE: The purpose of this study was to assess the 5-year survival and morbidity when radical hysterectomy and pelvic lymphadenectomy with pre- and postoperative radiation have been performed for IA2-IIB stage cervical cancer. STUDY DESIGN: During a 10 and a half year period between July, 1990 and December, 2000, 501 consecutive radical hysterectomies with bilateral pelvic lymphadenectomies were performed by the same gynecological surgeon for stage IA2, IB, IIA and IIB carcinoma of the cervix at the I. Department of Obstetrics and Gynecology, Semmelweis University Budapest. The patients were treated by pre- and postoperative irradiation as well. RESULTS: Perioperative complications apart from recurrence were minimal with no long-term morbidity. The absolute 5-year survival rates for the patients in stage IA2, IB1, IB2, IIA and IIB were 94,4%, 90,7%, 84,1%, 71,1% and 55,4%, respectively. The respective 5-year survival rates for patients without or with lymph node metastasis, were 94,5% and 33,3% in stage IB2, 81,7% and 48,7% in stage IIA and 70,2% and 36,5% in stage IIB, respectively. CONCLUSION: Nerve-sparing radical abdominal hysterectomy with pelvic lymph node dissection and pre- and postoperative irradiation remains the treatment of choice for most patients with early-stage and even in IIB-stage cervical cancer. The radicality and extent of lymph node dissection and parametrial resection should be individualized and tailored to tumor- and patient-related risk factors.

[Congenital absence of the ductus venosus associated with severe congenital heart malformation--case report and review of the literature]. / A ductus venosus veleszületett hiányának súlyos szívfejlodési rendellenességgel társult formája-- esetismertetés es az irodalom attekintése.

Congenital absence of the ductus venosus is a rare anomaly. The authors have found 57 cases in the literature. Their case was associated with a complex congenital heart disease, what occurs only in 10% of absent ductus venosus cases. In cases, where the umbilical vein connects directly to the right atrium, the volume overloading causes dilatation of the right atrium and ventricle, development of polyhydramnios and fetal hydrops. The diagnosed an umbilical vein directly connected to the right atrium, extreme systemic congestion, but no hydrops. In some fetuses this condition did not result hydrops, because there is compensation by the rich compliance of intrahepatic vascular beds. This case is an illustration that mild sonographic signs such a transient bradycardia in the early second trimester could be a sign of a heart malformation and can draw attention of the sonographer to other associated severe congenital heart disease.

Linkage analysis and molecular haplotyping of the dopamine D4 receptor gene promoter region.

OBJECTIVES: Polymorphic regions of the dopamine D4 receptor gene and its promoter region are in the focus of psychogenetic association studies. Besides the accurate phenotype characterization, highly reliable genotyping methods are also of outstanding importance in these works. METHODS: DNA samples of 598 healthy unrelated Caucasian individuals were used to validate the described molecular haplotyping methods and to determine the allele, genotype and haplotype frequencies and the linkage disequilibrium between the polymorphisms of the dopamine D4 receptor promoter region. RESULTS: We described a double genotyping system for the -521CT and -616CG polymorphisms, using a polymerase chain reaction restriction fragment length polymorphism or an allele-specific amplification. Allele and genotype frequencies of the novel -615AG single-nucleotide polymorphism are also determined (-615G=13.21%). For molecular haplotyping of the three single-nucleotide polymorphisms and a 120-bp duplication polymorphism, the allele-specific amplification was combined with restriction digestion. The results of the elaborated haplotyping methods were validated by molecular haplotyping of cloned fragments. CONCLUSIONS: The developed methods have been arranged into an 'economic' protocol that might be extended for higher reliability with a double haplotyping ('full mode'). Despite the close proximity of these sites, only a moderate linkage was found between the -615AG and -616CG (Delta(2)=0.162), between the -616AG and -521CT (Delta(2)=0.0221) and between the -615AG and -521CT single-nucleotide polymorphisms (Delta(2)=0.0346). The 120-bp duplication was shown to be in linkage equilibrium with any of the three single-nucleotide polymorphisms. Applications of these results should accelerate psychogenetic association studies of the dopamine D4 receptor gene.

Molecular prognostic markers in recurrent and in non-recurrent epithelial ovarian cancer.

BACKGROUND: The outcome and prognosis of ovarian cancer is highly variable. The objective of this study was to compare survival and clinicopathological prognostic factors with the expression levels of two matrix metalloproteinases (MMP) and fibronectin as tumor invasion and metastasis markers in ovarian cancer patients. MATERIALS AND METHODS: Histologically-verified epithelial ovarian tumours from 27 patients were studied. The latent and the activated forms of MMP-2 and MMP-9 were measured as gelatinase activity from tumour extracts and from serum and ascites samples by a zymographic technique. The fibronectin content was quantified by immunoblotting and densitometric analysis. Molecular marker levels were correlated to clinicopathological parameters such as survival and disease recurrence during the median postoperative follow-up period of 30 months. RESULTS: The levels of MMP-9 and fibronectin, but not those of MMP-2, were significantly higher in tumour tissues and in the ascites fluid of the recurrent patient group and the patient group who did not survive, as compared to the non-reccurent cases. CONCLUSION: Our data support that high expression of MMP-9 and fibronectin indicate poor prognosis for ovarian cancer patients who have similar clinicopathological prognostic factors.

[Improved outcome with sirolimus-cyclosporine regimen in high-risk renal transplant recipients]. / Sirolimus-ciclosporin alapú immunszuppresszív kezelés sikeres alkalmazása vesetranszplantáción atesett, rejectio szempontjábó1 magas kockázatú betegekben.

AIM: The immunosuppressive agents have a broad spectrum of adverse effects. In the absence of selective and specific drugs the decrease incidence and severity of side effects can be achieved by the combination of synergistic drugs only. Without wise selection and use of the combination of the potent immunosuppressive agents for the immunosuppressive maintenance therapy better results cannot be achieved without or fewer toxicities particularly in high-risk patients who lose their grafts prematurely. Therefore, a good combination will allow not only to reduce individual immunosuppressive drug induced toxicities but will also allow to achieve better graft and patient survival. MATERIAL AND METHODS: To assess the 6-year impact of a sirolimus-based regimen with, modest exposures to cyclosporine among three ethnic groups with different rejection risk, the authors performed a retrospective analysis of 470 renal transplant recipients who were treated contemporaneously: Group 1, high risk African Americans (n = 122); Group 2, moderate risk Hispanics (n = 132); Group 3, mild risk Caucasians (n = 216). Multivariate models were used to compare the outcomes in Group 1 with those of the other two groups. RESULTS: The cumulative incidence of acute rejection episodes over the entire follow-up period was similar among the groups: Group 1, 22.0%, Group 2, 24.2% and Group 3, 23.0%. Although there were no significant differences in overall or individual infection rates, Group 1 and 2 recipients displayed a significantly lower incidence of diarrhea at all times during follow-up compared with Group 3. All recipients showed similar rates of lymphocele formation. However, Group 1 displayed a reduced incidence and decreased severity of hypertriglyceridemia than Group 2 or Group 3 (89.3% vs. 97.2% vs. 93.2%), a similar incidence of hypercholesteremia (94.3% vs. 97.2% vs. 98.5%) was observed. The occurrence of post-transplant diabetes mellitus was greater in Group 1. than Group 3. but similar to Group 2. CONCLUSIONS: A concentration-controlled sirolimus-cyclosporine-prednisone regimen (with steroid withdrawal by 3 months) reduced the incidence of acute rejection episodes and increased 6-year graft survivals among high-risk African Americans to rates similar to other ethnic groups without an augmented toxicity profile.

Activation of deoxycytidine kinase in lymphocytes is calcium dependent and involves a conformational change detectable by native immunostaining.

Deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, plays a seminal role in the bioactivation of a wide array of cytotoxic nucleoside analogues. Recently, activation of dCK has been considered as a protective cellular response to a number of DNA-damaging agents in lymphocytes. Regarding the molecular mechanism of the enzyme activation, a post-translational modification by protein phosphorylation has been suggested. Here we provide evidence that both the activation process and the maintenance of the activated state require free cytosolic calcium. BAPTA-AM, a cell-permeable calcium chelator selectively inhibited the activation of dCK in a time- and concentration-dependent manner while extracellular calcium depletion had no effect. On the other hand, elevation of cytoplasmic calcium levels by thapsigargin did not potentiate the enzyme, referring to the permissive function of calcium in the activation process. Denaturing Western blots of extracts from lymphocytes incubated with 2-chlorodeoxyadenosine, aphidicolin and/or BAPTA-AM clearly demonstrated that dCK protein levels were unchanged during these treatments. However, a striking correlation was found between enzyme activity and the intensity of dCK-specific signals in native Western blots. Extracts from CdA-treated cells were much better recognized by the antibody raised against the C-terminal peptide of dCK than the BAPTA-AM-treated samples. These results indicate that the calcium-dependent activation of dCK is accompanied by a conformational change that renders the C-terminal epitope more accessible to the antibody.

Activation of deoxycytidine kinase by gamma-irradiation and inactivation by hyperosmotic shock in human lymphocytes.

Deoxycytidine kinase (dCK) is a key enzyme in the intracellular metabolism of deoxynucleosides and their analogues, phosphorylating a wide range of drugs used in the chemotherapy of leukaemia and solid tumours. Previously, we found that activity of dCK can be enhanced by incubating primary cultures of lymphocytes with substrate analogues of the enzyme, as well as with various genotoxic agents. Here we present evidence that exposure of human lymphocytes to 0.5-2 Gy dosage of gamma-radiation as well as incubation of cells with calyculin A, a potent inhibitor of protein phosphatase 1 and 2A, both elevate dCK activity without changing the level of dCK protein. When cells were gamma-irradiated in the presence of calyculin A, a more pronounced activation of dCK was observed. In contrast, both basal and stimulated dCK activities were reduced by hyperosmotic treatment of the cells. DNA repair determined by the Comet assay and by thymidine incorporation was induced by irradiation. Complete repair of gamma-irradiated DNA was detected within 1 hr following the irradiation along with dCK activation, but the rate of repair was not accelerated by calyculin A. These data provide evidence for the activation of dCK upon DNA damage and repair that seems to be mediated by phosphorylation of the enzyme, suggesting the role of dCK in DNA repair processes.

Large gastrointestinal stromal tumor presenting as an ovarian tumor. A case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors of the gastrointestinal tract localized mostly in the upper or medial part of the digestion tract. CASE: A colonic GIST in a young woman extended to the pelvis, giving the impression of an ovarian tumor. CONCLUSION: In the case of a pelvic mass, especially if other unusual anamnestic data and signs are present, the possibility of other than a gynecologic tumor has to be considered. Every effort should be made to identify the origin of the tumor and related anatomic structures, especially the ovaries.

Selective increase of dATP pools upon activation of deoxycytidine kinase in lymphocytes: implications in apoptosis.

Stimulation of the activity of deoxycytidine kinase (dCK), the principal deoxynucleoside salvage enzyme, has been recently considered as a protective cellular response to a wide range of agents interfering with DNA repair and apoptosis. In light of this, the potential contribution of dCK activation to apoptosis induction--presumably by supplying dATP or its analogues for the apoptosome formation--deserves consideration. Two-hour exposure of human tonsillar lymphocytes to 2-chloro-deoxyadenosine (CdA) led to a two-fold activation of dCK. This activation process was inhibited by pifithrin-alpha, a potent inhibitor of p53. When the dNTP pools were determined, both deoxypyrimidine triphosphate and dGTP pools were reduced after the treatments, while dATP levels elevated by 62%, 77% and 50% in the CdA, aphidicolin and etoposide-treated cells, respectively. We assume that dCK activation elicited by cellular damage might be a proapoptotic factor in terms of generating dATP well before the release of cytochrome c and deoxyguanosine kinase from mitochondria.