Changes in retinoblastoma gene expression during cervical cancer progression

The role of tumour suppressor genes in the development of human cancers has been studied extensively. In viral carcinogenesis, the inactivation of suppressor proteins such as retinoblastoma (pRb) and p53, and cellular oncogenes overexpression, such as c-myc, has been the subject of a number of investigations. In uterine-cervix carcinomas, where high-risk human papillomavirus (HPV) plays an important role, pRb and p53 are inactivated by E7 and E6 viral oncoproteins, respectively. However, little is known about the in situ expression of some of these proteins in pre-malignant and malignant cervical tissues. On the other hand, it has also been demonstrated that c-myc is involved in cervical carcinogenesis, and that pRb participates in the control of c-myc gene expression. By using immunostaining techniques, we investigated pRb immunodetection pattern in normal tissues, squamous intraepithelial lesions (SILs) and invasive carcinomas from the uterine cervix. Our data show low pRb detection in both normal cervical tissue and invasive lesions, but a higher expression in SILs. C-Myc protein was observed in most of the cellular nuclei of the invasive lesions, while in SILs was low. These findings indicate a heterogeneous pRb immunostaining during the different stages of cervical carcinogenesis, and suggest that this staining pattern could be a common feature implicated in the pathogenesis of uterine-cervix carcinoma.     

Clonal proliferation of cyclin D1-positive mantle lymphocytes in an asymptomatic patient: an early-stage event in the development or an indolent form of a mantle cell lymphoma?

Mantle cell lymphoma (MCL) is a B-cell neoplasm with a relatively aggressive clinical course. There is a very small subgroup of patients who present with atypical lymphocytes in peripheral blood, with or without lymphocytosis, lymphadenopathy, or splenomegaly, and with an indolent clinical course. They frequently show mutated IgV(H) genes and CD5 negativity. We report an asymptomatic elderly patient who presented with a single submandibular lymphadenopathy. The biopsy showed immunophenotype and t(11;14)(q13;q32) consistent with MCL. The abnormal lymphoid population was also detected in peripheral blood and bone marrow. The patient has remained asymptomatic for 5 years without receiving any therapy. It is uncertain whether these cases represent an early-stage event in the development or an indolent form of MCL. The existence of such asymptomatic patients with an indolent clinical course should induce a strict clinical judgment in terms of therapeutic decisions.     

Influence of renal nerves on renal function during development

The present review summarizes recent studies describing the role of renal sympathetic innervation in the regulation of renal function during development. The afferent renal innervation appears early during fetal life and probably precedes the development of efferent renal nerves. There is suggestive evidence that renal nerves are required for the proper development of the kidney and that neurotrophic growth factors play an important role in renal embryogenesis and in renal tubular differentiation. Renal sympathetic innervation modulates renal hemodynamics early during development. Renal nerve stimulation during -adrenoceptor blockade produces renal vasodilation in fetal and newborn animals but not in adults. Unlike the effect of renal nerves on fetal renal hemodynamics which is observed in the young fetus, the role of renal sympathetic nerves in modulating fluid and electrolyte homeostasis seems to develop during late gestation. Recent studies have also shown that renal nerves play an important role in regulating renin secretion during the transition from fetal to newborn life. For example, renal denervation during fetal life suppressed the physiological rise in plasma renin activity associated with delivery and decreased renal renin mRNA levels after birth. Taken together, these studies suggest that renal nerves influence fetal renal development and that the influence of renal sympathetic innervation on renal hemodynamics and function changes with maturation.     

Partial epiglottectomy as a possible treatment for globus pharyngeus?

Globus pharyngeus is a relatively common complaint in an ear, nose, and throat consulting room and may account for 3–4% of outpatient referrals. The cause is still unknown, although a number of hypotheses have been suggested. Between 40% and 75% of the patients remain symptomatic despite any treatment regimen. Thirteen patients from a group of 124 with the diagnosis of globus pharyngeus and no response to medical treatment were treated with partial epiglottectomies. One year after the surgery all but one patient were free of symptoms. Our experience indicates that partial epiglottectomy can be a good treatment for those patients with globus pharyngeus in whom no cause is found after all studies are performed or when medical treatment fails. Received: 19 October 1999 / Accepted: 16 December 1999     

Potent induction of human colon cancer cell uptake of chemotherapeutic drugs by N-myristoylated protein kinase C-α (PKC-α) pseudosubstrate peptides through a P-glycoprotein-independent mechanism

Phorbol ester protein kinase C (PKC) activators and PKC isozyme over-expression have been shown to significantly reduce intracellular accumulation of chemotherapeutic drugs, in association with the induction of multidrug resistance (MDR) in drug-sensitive cancer cells and enhancement of drug resistance in MDR cancer cells. These observations constitute solid evidence that PKC plays a significant role in the MDR phenotype of cancer cells. PKC-catalyzed phosphorylation of the drug-efflux pump P-glycoprotein was recently ruled out as a contributing factor in MDR. At present, the sole drug transport-related event that has been identified as a component of the role of PKC in MDR is PKC-induced expression of the P-glycoprotein-encoding gene mdr1. The objective of this study was to test the hypothesis that PKC can modulate the uptake of chemotherapeutic drugs in cancer cells independently of P-glycoprotein. We analyzed the effects of selective PKC activators/inhibitors on the uptake of radiolabelled cytotoxic drugs by cultured human colon cancer cells that lacked P-glycoprotein activity and did not express the drug efflux pump at the level of message (mdr1) or protein. We found that the selective PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly reduced uptake of [¹⁴C] Adriamycin and [³H] vincristine in human colon cancer cells devoid of P-glycoprotein activity, and that PKC-inhibitory N-myristoylated PKC- pseudosubstrate synthetic peptides potently and selectively induced uptake of the cytotoxic drugs in the phorbol ester-treated and non-treated colon cancer cells. TPA treatment of the cells did not induce expression of either P-glycoprotein or its message mdr1. In contrast with [¹⁴C]Adriamycin and [³H] vincristine uptake, [³H] 5-fluorouracil uptake by the cells was unaffected by TPA and reduced by the PKC-inhibitory peptides. These results indicate that PKC activation can significantly reduce the uptake of multiple cytotoxic drugs by cancer cells independently of P-glycoprotein, and that N-myristoylated PKC- pseudosubstrate peptides potently and selectively induce uptake of multiple cytotoxic drugs in cultured human colon cancer cells by a novel mechanism that does not involve P-glycoprotein and may involve PKC isozyme inhibition. Thus, N-myristoylated PKC- pseudosubstrate peptides may offer a basis for the development of agents that reverse intrinsic drug resistance in human colon cancer.     

Unhealthy eating behaviour in adolescents

In recent years, eating disorders (Anorexia and Bulimia Nervosa) have increased and are appearing at increasingly younger ages. They affect predominantly adolescent females 12 to 25 years of age. The objective of this study of adolescents is to detect and discuss unhealthy eating behaviour, defined by either of two factors: (1) following a slimming diet not advised or supervised by any person trained in health care; or (2) eating very large quantities at irregular times, not related to anxiety or stress. A transversal study has been undertaken of 630 school children of 14–18 years of age (average: 15.9 years) in Cádiz (Andalucia, Spain), using an anonymous self-reporting questionnaire to collect data on personal and educational situation, on eating habits, on nutritive intake and knowledge of nutrition, and on dieting and physical exercise. The study has considered averages, ratios, statistical significance (x ²) and, as a measure of risk, the Disequality Ratio of Prevalence (DRP). Anomalous eating behaviour was detected in 46.3% (292), with females predominant by a ratio of 2:1. Comparing groups with anomalous and with normal eating habits, significant differences were detected in respect of: perception of body image (p<0.001), frequency of weighing oneself (p<0.05), periods of abstinence from eating (DRP 1.66; 95% confidence interval (CI): 1.66–2.37), provocation of vomiting (DRP 2.02; 95% CI: 1.13–3.65), use of laxatives (DRP 4.25; 95% CI: 1.08–9.63), and the exclusion of certain meals and types of food, mainly bread and cereals, fats and sugars. Conclusions are drawn on the substantial scale of unhealthy eating behaviour among adolescents in Cadiz. More adequate education on personal health and related social issues should be provided.     

Restraint-induced stress ulcer. I. Hypothalamic,urinary, and adrenal biochemical studies

The purpose of these experiments was to study the incidence of stress ulcers in restrained rats and to correlate it with hypothalamic and adrenal cortical and medullary activity, with and without vagotomy. A total of 217 adult rats were used, grouped into 56 sets, and distributed at random in 5 experimental groups. Restraint was followed by a 79% incidence of ulceration in the glandular portion of the gastric mucosa. Vagotomy made these worse (p<0.01). Hypothalamic levels of catecholamines and serotonin showed no significant changes. Urinary measurements revealed decreased excretion of 17-ketosteroids (p<0.001), increased excretion of uropepsinogen (p<0.01), and no significant changes in vanillylmandelic acid among the rats submitted to immobilization. In the adrenal glands of stressed animals, there was a decreased level of catecholamines (p<0.01) and no significant changes in corticosteroid content (17-ketosteroids). These results suggest that hypothalamic stimulation and the participation of the adrenal glands are not essential factors in the pathogenesis of restraint-induced experimental stress ulcer.     

Hamartoma mamario: un tumor infrecuente

We present a case of hamartoma of the breast. This is an infrequent tumour that requires the correct diagnosis to distinguish it from other histopathology types because it has a better prognosis. The characteristic image from a mammogram is useful in its diagnosis.     

The IAEA/WHO TLD postal dose quality audits for radiotherapy: a perspective of dosimetry practices at hospitals in developing countries.

BACKGROUND AND PURPOSE: The IAEA/WHO TLD postal programme for external audits of the calibration of high-energy photon beams used in radiotherapy has been in operation since 1969. This work presents a survey of the 1317 TLD audits carried out during 1998-2001. The TLD results are discussed from the perspective of the dosimetry practices in hospitals in developing countries, based on the information provided by the participants in their TLD data sheets. MATERIALS AND METHODS: A detailed analysis of the TLD data sheets is systematically performed at the IAEA. It helps to trace the source of any discrepancy between the TLD measured dose and the user stated dose, and also provides information on equipment, dosimetry procedures and the use of codes of practice in the countries participating in the IAEA/WHO TLD audits. RESULT: The TLD results are within the 5% acceptance limit for 84% of the participants. The results for accelerator beams are typically better than for Co-60 units. Approximately 75% of participants reported dosimetry data, including details on their procedure for dose determination from ionisation chamber measurements. For the remaining 25% of hospitals, who did not submit these data, the results are poorer than the global TLD results. Most hospitals have Farmer type ionisation chambers calibrated in terms of air kerma by a standards laboratory. Less than 10% of the hospitals use new codes of practice based on standards of absorbed dose to water. CONCLUSION: Despite the differences in dosimetry equipment, traceability to different standards laboratories and uncertainties arising from the use of various dosimetry codes of practice, the determination of absorbed dose to water for photon beams typically agrees within 2% among hospitals. Correct implementation of any of the dosimetry protocols should ensure that significant errors in dosimetry are avoided.