The frequency of Chlamydia trachomatis infection in women with intraepithelial neoplasia of the uterine cervix

A case of a rare form of Sanfilippo disease, mucopolysaccharidosis type III D is presented. The cause of the disease is a deficit of N-acetylglycosamine-6-sulfate sulfatase. Differences in clinical course and symptoms with type A and B Sanfilippo disease are shown (later presentation of symptoms, milder course, lack of distinct psychomotor regression and differences in characteristic phenotypic traits, such as facial features, joint contracture, tall height). It is suggested that type III D mucopolysaccharidosis be taken into account in the differentiation of mental retardation syndromes with hyperactivity.     

Inflammatory stromal reaction in epithelial neoplasia of the uterine cervix in correlation with HPV infection

260 cases of women with epithelial neoplasias of the uterine cervix were studied: HPV infection was detected by DNA in situ hybridization and serology, simultaneously structure and intensity of stromal inflammatory reaction (SR) were evaluated (semiquantitatively) as well as standard clinical immunological parametres investigated by serology. Results proved the same character of SR in intraepithelial lesions and invasive carcinomas and the intensity of SR increasing in relation to the gravity of epithelial dysplasia. There was not found any significant difference in SR between cases with detected HPV infection and cases lacking it. Summarized immunological parametres were in limits of normal reference range.     

The susceptibility of the postpartum and postabortal cervix and uterine cavity to infection with attenuated rubella virus

To determine the susceptibility of the postpartum and postabortal genital tract to infection with attenuated rubella virus, 30 patients with negative hemagglutination inhibition (HI) titers were studied. Following inoculation with Cendehill or RA 27/3 vaccine, viral cultures of the cervix and uterine cavity were obtained with blood specimens to evaluate serologic conversion. Attenuated rubella virus was not isolated in any patient; seropositive conversion was achieved in 24 women. The significance of these findings related to wild rubella virus infection is discussed.     

Morphology of lesions of the uterine cervix and human papillomaviruses

The question of psychophysiological reactivity of borderline hypertensives is still controversial. METHODS: Young males with borderline blood pressure levels and normotensive controls were recruited during a routine examination. Samples of study I comprised 19 subjects, samples of study II 18 subjects. Two stressors were presented (distressing movie, mental arithmetic), each followed by a recovery phase. Systolic and diastolic blood pressure, heart rate, and electrodermal parameters were assessed repeatedly. RESULTS: Borderline hypertensives showed greater reactions to stressors in systolic blood pressure only. Changes in percentage of baseline levels were essentially the same. Recovery after stress did not differ between groups. CONCLUSION: Only moderate support is given to the hypothesis that borderline hypertensives show increased and slowly recovering psychophysiological responses.     

Human papillomaviruses and carcinogenesis of the uterine cervix: future prospects in the domain of detection and prevention

It is now admitted that certain genotypes of human papillomavirus (HPV), mainly HPV types 16 and 18, play an etiological role in the origin of the great majority of invasive carcinomas of the uterine cervix and their intraepithelial precursors. Such an evidence has modified our understanding of the natural history of cervical cancer and should result in new approaches for the early diagnosis and prevention of precursor lesions. Sensitive, specific and reliable HPV detection tests have been progressively designed but their use as routine tests requires multicentric studies, involving large series of women, to evaluate their usefulness in the clinical management or the screening of patients and to establish their limits and cost-effectiveness. It is already most likely that the association of HPV detection tests to cervicovaginal cytology would increase the detection rate of high-grade intraepithelial neoplasia and constitute a means for quality control in cytology. The viral origin of most cancers of the uterine cervix paves the way for their prevention by vaccination against the main oncogenic HPV genotypes and provides hope for specific immunotherapy of associated neoplasia.     

Nitric oxide mediated inhibition of contractile activity in the human uterine cervix

Nitric oxide (NO) is an important modulator of contractile activity in various tissues. The aim of the present study was to investigate the possible existence of an NO system within the human uterine cervix and to study the effects of NO on the cervix in early pregnancy. Cervical tissue specimens were obtained from 24 women in connection with first trimester legal abortion. NADPH diaphorase staining was used to identify nitric oxide synthase activity within the cervical tissue. Cylindrical tissue specimens were mounted in organ bath chambers for isometric registration of contractile activity. The presence of a functional NO system in the cervix was investigated by adding either sodium nitroprusside or spermine NONOate, two different NO donors, or 8-bromo cGMP, an analogue of the second messenger cyclic guanosine monophosphate (cGMP), to the organ baths. Positive NADPH diaphorase staining was clearly observed in the walls of blood vessels, in cervical smooth muscle cells, and cells scattered in the connective tissue. The NO donating drugs sodium nitroprusside and spermine NONOate both caused a dose-dependent inhibition of spontaneous contractile activity with significant inhibition at concentrations of 10(-5) and 10(-7) M respectively. Furthermore, the participation of NO in the regulation of cervical contractility was indicated by a significant concentration-dependent inhibition of spontaneous contractions when 8-bromo cGMP (10(-5)-10(-3) M) was added to the organ baths. The study indicates the existence of an NO system within the human uterine cervix and a role of NO in control of cervical function.     

The role of telomerase for pancreatic carcinogenesis in human and hamster

Telomerase activity and terminal restriction flagment (TRF) length were investigated in human and hamster pancreatic duct adenocarcinomas. In the hamster primary and transplantable pancreatic carcinomas and cell lines, telomerase activity increased 86 to 215.7 times relative to the levels in normal spleen and pancreas, and reduction of TRF length was observed. In 38 human pancreatic ductal carcinomas, 32 (84%) exhibited increased telomerase activities with no apparent relation to the histological type of tumor, tumor size, regional lymph node involvement and distant metastasis. These results suggest that telomerase play an important role for pancreatic duct carcinogenesis.     

Identification and biosynthesis of fibrinogen in human uterine cervix carcinoma cells

Fibrinogen has been detected in ME-180 human uterine cervix carcinoma cells, and synthesis of fibrinogen by ME-180 cells has been measured using [35S] L-methionine incorporation. Expression of mRNA for the B beta-chain of the fibrinogen in ME-180 cells has been identified by PCR-assisted mRNA amplification. The A alpha-, B beta-, and gamma-chains of fibrinogen synthesized by ME-180 cells were chemically and immunologically identical to those of plasma fibrinogen. These findings suggest that fibrinogen is present and synthesized in ME-180 human uterine cervix carcinoma cells, and that fibrinogen plays a role in these malignant tumor cells.     

Chemoradiotherapy in cancers of the uterine cervix

In order to determine the possible role of the cystic fibrosis transmembrane regulator (CFTR) gene in pulmonary diseases not due to cystic fibrosis, a complete screening of the CFTR gene was performed in 120 Italian patients with disseminated bronchiectasis of unknown cause (DBE), chronic bronchitis (CB), pulmonary emphysema (E), lung cancer (LC), sarcoidosis (S) and other forms of pulmonary disease. The 27 exons of the CFTR gene and their intronic flanking regions were analyzed by denaturing gradient gel electrophoresis and automatic sequencing. Mutations were detected in 11/23 DBE (P = 0.009), 7/25 E, 5/27 CB, 5/26 LC, 5/8 S (P = 0.013), 1/4 tuberculosis, and 1/5 pneumonia patients, and in 5/33 controls. Moreover, the IVS8-5T allele was detected in 6/25 E patients (P = 0.038). Four new mutations were identified: D651N, 2377C/T, E826K, and P1072L. These results confirm the involvement of the CFTR gene in disseminated bronchiectasis of unknown origin, and suggest a possible role for CFTR gene mutations in sarcoidosis, and for the 5T allele in pulmonary emphysema.     

Alveolar rhabdomyosarcoma of the uterine cervix

Porphyria cutanea tarda is characterized by severe connective tissue damage in sun-exposed skin. The regulated synthesis and degradation of the extracellular matrix by various matrix metalloproteinases (MMPs) determine its amount and composition within the skin. In this study, we therefore asked whether long-wave ultraviolet irradiation (340-450 nm) in conjunction with uroporphyrin I could modulate the synthesis of MMPs with substrate specificities for dermal (collagens I, III, V; proteoglycans) and basement membrane components (collagens IV, VII; fibronectin; laminin) and whether synthesis of the counteracting tissue inhibitor of metalloproteinases is also affected. After irradiation of uroporphyrin-pretreated fibroblasts, specific mRNAs of MMP-1 and MMP-3 increased concomitantly up to 2.7-fold compared with ultraviolet-irradiated cells and up to 10-fold compared with mock-irradiated or uroporphyrin I-treated controls. In contrast, mRNA levels of tissue inhibitor of metalloproteinases remained unaltered. Similar results were obtained by immunoprecipitation. Gelatin and casein zymography revealed increased proteolytic activity of MMP-2 and MMP-3 in blister fluids of patients with porphyria cutanea tarda, indicating that similar events may occur in vivo. Using deuterium oxide as enhancer and sodium azide as quencher of singlet oxygen, we could increase or reduce MMP synthesis, suggesting that singlet oxygen is the major intermediate in the upregulation of MMPs after irradiation of uroporphyrin-pretreated fibroblasts. Taken together, our results show that ultraviolet irradiation alone, and to a greater extent in conjunction with uroporphyrin I, results in an unbalanced synthesis of MMPs that may contribute to the destruction of the dermis and basement membrane, leading to blistering and accelerated photoaging in porphyria cutanea tarda patients.     

The long-term course of carcinoma in situ of the uterine cervix

The malignant potential of carcinoma in situ (CIS) of the uterine cervix has been the subject of great controversy. Despite refinements and additions to knowledge in this area, few reports on the long-term course of the disease have appeared in the past decade. Recent developments in diagnostic and therapeutic techniques coupled with changes in the patient population with this disease have prompted renewed interest in conservative management. Results of long-term observation of a group of patients followed initially without ablative therapy are reported. The data indicate that CIS of the uterine cervix is not the inevitably progressive disease that it has been considered to be. Unequivocal invasive cancer develops in only a small percentage of cases and can be controlled, if not cured, by current therapeutic modalities. The intraepithelial lesion, however, tends to persist despite conization, and eventually requires ablative therapy in most cases. Conservative procedures should be regarded as temporizing, at least until their long-term benefits can be recorded.     

Sonographic evaluation of the uterine cervix

Ultrasonographic evaluation of the uterine cervix has been shown to help predict patients who may be at an increased risk for preterm delivery. The use of ultrasound in at-risk patients may improve the selection of those needing obstetric intervention, which therefore, may improve outcome and lower overall health care costs. Cervical competence, once thought to be a categorical variable, should now be thought of as a continuous variable, as the shortest cervical lengths are found in those women with a history of very early preterm delivery (> 24 weeks). Adjunctive tests, such as fetal fibronectin Bishop scoring and bacterial vaginosis may help to improve the accuracy of prediction of preterm birth; therefore a multifaceted risk approach to preterm birth is suggested in this article.     

Neuroendocrine differentiated carcinoma of the uterine cervix

Cervical neuroendocrine carcinomas (CNC) are rare tumors. The term includes the cervical carcinoid, the small cell (oat-cell) carcinoma and the primitive neuroectodermal tumor (PNET). Between 1979 and 1993 eight CNC out of 788 cervical carcinomas were identified by conventional light microscopy and immunohistochemistry. Three tumors were small cell carcinomas with positive staining for NSE (6/8 tumors) and chromogranin A (2/8). In one case a PNET was diagnosed by identifying rosette like structures and negative immunohistochemistry for neuroendocrine markers. Two patients (including PNET) died of disease 3.1 (1.3 to 4.8) years after diagnosis. The others showed no evidence of disease after a mean follow up to 4.4 years. Three of them got pelvic radiation postoperatively. Four tumors showed foci of squamous cell carcinoma [3] and adenocarcinoma [2]. There is no evidence, that these foci influence the prognosis on CNC. Therefore, it is important to recognize the neuroendocrine component, as this type of carcinoma requires special therapeutic considerations. The authors favour the metaplastic origin of CNC from a multipotent (endocervical) stem cell.     

The role of receptors in multistage carcinogenesis

The principal characteristic of neoplasia is its inherited alteration of genetic expression. The regulation of gene expression may be altered both by mutational events and by environmental mediators. During carcinogenesis the permanent alterations in genetic expression resulting from mutations occur primarily during the final stage of progression when biological malignancy becomes evident. During the preceding reversible stage of promotion, alteration and genetic expression are the result of the chronic stimulation of an altered (initiated) cell responding to the environmental mediator or promoting agent. A major mechanism of this effect occurs by receptors exhibiting specificity for the mediator and for their interaction with the genome. Withdrawal of the promoting agent prior to the genetic alterations characteristic of the stage of progression leads to a reversal of the effects of the promoting agent and the death by apoptosis of most cells in the stage of promotion. Carcinogenesis mediated by the chronic ligand (promoting agent)-receptor interaction increases the probability of the development of the stage of progression; thus alteration or prevention of the stage of promotion by removal of the promoting agent or inhibition of its action remains the best opportunity for cancer prevention. Application of the reversible promoting agent-receptor interaction to specific environmental circumstances where such plays a major role can lead to a more rational risk estimation of promoting agents for the human population.