Association of LAR-like receptor protein tyrosine phosphatases with an enabled homolog in Hirudo medicinalis

Receptor protein tyrosine phosphatases (RPTPs) are thought to play important functions in pathfinding and target recognition by growing neuronal processes. The leech RPTPs HmLAR1 and HmLAR2 are expressed selectively by central neurons, Comb cells, and peripheral muscle tissues in the Hirudo medicinalis embryo. To explore the functions of HmLARs, we have sought to determine their physiological substrates. We report here the cloning and embryonic expression of Lena, the leech homolog of Enabled, a cytosolic protein implicated in actin-based cell motility. Lena is expressed in embryonic central neurons and in the Comb cell. We present experimental evidences indicating that Lena associates selectively with the intracellular domain of HmLAR1 and HmLAR2. Additionally, RNA interference (RNAi) of HmLAR1 in intact leech embryos leads to the hyperphosphorylation of Lena. We propose, therefore, that Lena is an in vivo substrate of HmLAR1 in neurons and perhaps of HmLAR2 in the Comb cells.     

A Bayesian analysis of bivariate ordinal data: Wisconsin epidemiologic study of diabetic retinopathy revisited

In many biomedical experiments one may often encounter bivariate data which are component-wise ordinal. The data set of the ophthalmologic experiment of the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) is an example of such data. Several authors considered the analysis of such data from different viewpoints. The present work reviews the existing literature based on the WESDR data and on the basis of some latent variables provide the technique for analysing such data more easily in a Bayesian framework. Computation supports the methodology to a great extent. A comparison between our approach and the likelihood based approach considered by Kim has also been made.     

Impairment of stimulation by estrogen of insulin-activated nitric oxide synthase in human breast cancer

Nitric oxide (NO) is reported to have several important effects in the control of neoplasm. We have reported before the presence of an insulin-activated constitutive form of membrane-bound nitric oxide synthase (IANOS) in various cells. Since the insulin-induced NO synthesis by IANOS could have important consequences on the pathophysiology of neoplastic cells, the role of estrogen on the activity of IANOS in malignant and nonmalignant breast tissue as well as in erythrocytes in breast cancer patients was determined. It was found that the IANOS activity of nonmalignant breast tissue was maximally stimulated by 4-fold over the basal activity in the presence of physiologic amounts of estrogen (8-32 nM). The enzymic activity was, however, inhibited by estrogen both below and above this range when compared to appropriate controls. In contrast, both the basal IANOS activity and the stimulatory effect of estrogen was markedly impaired in malignant breast tissue and in erythrocytes in these patients. It was also noted that tamoxifen, a widely used nonsteroidal compound in breast cancer, mimicked estrogen both in the stimulation and in the inhibition of IANOS activity in both of the tissues. These results indicated the probable existence of a novel pathway for estrogen effect independent of nuclear receptor for the stimulation of IANOS activity that might have important consequences in breast cancer and suggested that some of the beneficial effects of tamoxifen could be related to its estrogen-mimicking effect on IANOS independent of hormone-responsive elements sequence in the DNA.     

Accelerated partial breast irradiation: an updated report from the American Brachytherapy Society

Logistical barriers of time and travel created by the conventional six week course of radiotherapy prevent many women from pursuing breast conservation treatment. For the past 12 years, Accelerated Partial Breast Irradiation (APBI) has been investigated as a potential alternative treatment approach in women with early stage breast cancer. The ability to complete treatment in five days has the potential to provide additional women with the option of breast conservation. The validity of this APBI is supported in the study of in-breast recurrence patterns, pathologic data and the clinical treatment experience. The review of the recent data on contemporary APBI reveals that patient selection criteria and brachytherapy quality assurance are clearly critical components and necessary to assure a successful treatment outcome. This updated report from the American Brachytherapy Society on Accelerated Partial Breast Irradiation reviews the appropriate background data supporting this treatment approach with conclusions regarding patient selection criteria and treatment delivery.     

Poor outcome and quality of life in female patients undergoing secondary surgery for recurrent peptic ulcer disease

Secondary peptic ulcer surgery is uncommon given the success of a wide variety of medical therapies, plus the good outcome expected after primary peptic ulcer surgery. Early reports of secondary peptic ulcer surgery in the 1950s and 1960s suggested good long-term outcome in most patients; however, recent data suggest that patients operated in the Helicobacter pylori era have a worse outcome. We have attempted to quantify the poor outcome in these patients and measure the effect of sex, a previously unrecognized risk factor for poor outcome after peptic ulcer surgery. We reviewed the outcomes of 35 patients who underwent secondary peptic ulcer surgery for symptoms of persistent or recurrent peptic ulcer symptoms or complications of the condition. These patients were compared to a "control" group of patients to determine long-term quality of life as measured by the SF-36 and Visick scores (average follow-up 60 months). Visick and SF-36 scores were obtained through telephone interviews. The two groups of patients were age matched to eliminate age as a variable in the SF-36 results. There were more females than males in the secondary peptic ulcer surgery group (4.5/1 female-to-male ratio). Although perioperative mortality was zero for both groups, patients undergoing secondary peptic ulcer surgery had a high number of complications (57% of patients had complications). Patients undergoing secondary peptic ulcer surgery scored lower in seven of the eight subclasses of the SF-36 questionnaire compared to their age-matched cohorts. In contrast, average Visick scores showed slight improvement for three out of four symptoms reported. Immediate postoperative complications were not related to long-term quality of life issues. Secondary peptic ulcer surgery is more prevalent in females than in males. Although secondary peptic ulcer surgery is partially effective in alleviating symptoms, quality of life is poor. Presented at the Forty-Second Annual Meeting of The Society for Surgery of the Alimentary Tract, Atlanta, Georgia, May 20–23, 2001 (poster presentation).     

Human papillomavirus (HPV) and cervical cancer

Epidemiologic studies have consistently shown that the most important risk factor for cervical cancer relates to sexual activity and a sexually transmitted agent, probably a virus, is the principal causative agent. In recent years, much attention has been focused on the human papillomavirus (HPV) as the causative agent. The compelling epidemiologic evidence of the role of HPV in cervical cancer is complemented by equally strong data on the role of oncoproteins E6 and E7 of high-risk HPV strains in the molecular pathogenesis of cervical cancer. Incidence and mortality from cervical cancer have been decreasing steadily in most developed countries, but is the leading female cancer in developing countries. This variation in incidence is explicable in terms of differing levels of risk behaviour and population screening facilities and uptake. With better understanding of the aetiopathogenesis, vaccination against HPV is becoming a reality. This may be particularly useful in developing countries, where it is proving difficult to implement effective screening programmes.     

Mechanically evoked perioral reflexes in premature and term human infants

Neurophysiological assessment of the preterm human neonatal oromotor system has been limited due to their fragile medical state, and methodological limitations. A new, noninvasive technology known as the actifier was developed and used to evoke perioral motor unit activity during non-nutritive suck in preterm infants. A significant ontologic trend for the early component of the perioral reflex (R1) was discovered in the context of spontaneous, centrally-patterned oromotor behavior.