Differential effects of protein kinase a sub-units on chinese-hamster-ovary cell cycle and proliferation

It has been shown that a marked increase in the levels of Rlα sub-units and a decrease in RIIβ sub-unit levels correlate with neoplastic transformation or with the mitogenic response of normal cells to hormones and growth factors. The selective down-regulation of RIα and the following induction of RIIβ determine cell-growth arrest and differentiation of several cancer cells. To directly address the question whether the 2 protein-kinase-A(PKA) isoforms play different roles in the control of proliferation and cell-cycle distribution, we introduced and over-expressed the different PKA sub-units in Chinese-hamster-ovary (CHO) cells via retroviral-vector-mediated gene transfer. Whereas CHO cells treated with RIα anti-sense oligodeoxynucleotides were growth arrested and accumulated in the G₀/G₁ phases of the cell cycle, infection of CHO cells with a retroviral vector in order to over-express RIα determined growth advantages in monolayer conditions and substantially increased their cloning efficiency in soft agar. These events correlated with a sustained percentage of cells in S phase induced by RIα over-expression in the infected cells. In contrast, CHO cells infected with retroviral vectors over-expressing either a RIIβ sub-unit or a Cα catalytic sub-unit of PKA exhibited growth arrest within a few days of culture and accumulated in the G₂-M phase of the cell cycle. The results of our study demonstrate that the different PKA sub-units play different and specific roles in the control of cell growth and cell-cycle distribution.     

Evaluation of a measurement strategy for Parkinson's disease: Assessing patient health-related quality of life

This study evaluated the feasibility and psychometric properties of self-completed and telephone interview versions of a patient health-related quality-of-life (HQL) questionnaire for Parkinson's disease that included the SF-36 Health Survey (SF-36), the Parkinson's Disease Questionnaire (PDQ-39), and the Medical Outcomes Study Sexual Function Survey. Parkinson's disease patients (n = 150) completed the questionnaire twice: once at the study site and once over the telephone in a randomized order. Ninety-four percent of enrolled patients completed the first HQL assessment and 88% completed both assessments. Cronbach's exceeded 0.70 for all scales except for the self-completed PDQ-39 Social Support subscale (0.57) and the telephone interview PDQ-39 Social Support (0.60) and Cognitions (0.67) subscales and the SF-36 General Health (0.60) and Social Function (0.61) subscales. There were no statistically significant differences in mean HQL scale scores across the two modes of administration. Mean scores for 3 of the PDQ-39 subscales and the Summary Index were significantly poorer (p < 0.05) for patients at later clinical stages. Similarly, patients with dyskinesias reported significantly poorer scores for 4 of the PDQ-39 subscales and the Summary Index and patients with self-reported comorbidities reported poorer SF-36 Physical Function and General Health subscale scores than patients without dyskinesias and comorbidities, respectively. This study suggests that the self-completed and telephone interview versions of the patient HQL questionnaire are feasible and valid for future clinical trial applications.     

Laparoscopy-assisted orchidopexy: an ideal treatment for children with intra-abdominal testes

BACKGROUND AND PURPOSE: The investigation of a child with a nonpalpable testis is probably the most frequent indication for laparoscopy in pediatric patients. The objective of this study was to evaluate the results and advantages of laparoscopy-assisted orchidopexy performed without dividing the spermatic vessels. PATIENTS AND METHODS: During a 3-year period, 85 boys with nonpalpable testes (NPT) (91 testes overall) underwent laparoscopic diagnostic exploration. Twenty-five patients (27.4%) showed an intra-abdominal testis (IAT): 24 underwent a laparoscopy-assisted orchidopexy (LAO) without sectioning of the spermatic vessels, and one, whose inner spermatic vessels were not adequately long for LAO without tension, underwent a two-step Fowler-Stephens (FS) procedure. The technique consists of dissection and mobilization of the inner spermatic vessels and the vas deferens from the posterior peritoneum, sectioning of the gubernaculum attachments, and bringing down of the testis into the scrotum through the internal inguinal ring, if open, or through a neo-inguinal ring created medial to the epigastric vessels. RESULTS: Surgery lasted between 40 and 80 minutes (median 60 minutes). All the testes were brought down into the scrotum. There was only 1 (4%) intraoperative complication, which occurred in the second patient operated on with this procedure. He experienced an iatrogenic rupture of the spermatic vessels secondary to excessive traction. CONCLUSION: Laparoscopic orchidopexy is the logical extension of diagnostic laparoscopy for the evaluation of NPT. Concerning the technique, we believe that LAO with intact spermatic vessels could be considered the treatment of choice in the patient with IAT, as it does not affect normal testicular vascularization. Alternatively, in the case of very high IAT (more than 3 cm from IIR), an FS procedure may be considered.     

Influence of chronic ethanol consumption on toxic effects of 1,2-dichloroethane: glycolipoprotein retention and impairment of dolichol concentration in rat liver microsomes and Golgi apparatus

Our previous investigations demonstrated that 1,2-dichloroethane (DCE) and chronic ethanol treatment separately are able to impair glycoprotein metabolism and secretion, and reduce dolichol concentration in liver membranes. The purpose of this study was to investigate whether chronic ethanol consumption can induce potentiation of rat liver damage due to DCE haloalkane used in several chemical processes and in agriculture. Rats were given 36% of their total energy as ethanol in the Lieber-DeCarli liquid diet for 8 weeks (CH group). The pair-fed control group received an isocaloric amount of dextrine-maltose (PF group). "In vitro" experiments: the DCE (6.5 mM) treatment of isolated hepatocytes from CH rats enhanced glycoprotein retention and further reduced glycoprotein secretion and 14C-glucosamine incorporation compared to the hepatocytes from CH or from PF and DCE treated rats. "In vivo" experiments: a marked decrease of dolichol concentration in microsomes (in which dolichyl phosphate is rate-limiting for the initial glycosylation of protein) and in Golgi membranes (in which total dolichol is very important for membrane permeability, fluidity and vesicle fusion) was observed in CH rats acutely treated with 628 mg/kg bw of DCE (CH+DCE) compared with CH or PF+DCE treated rats. These data suggest that chronic ethanol consumption increases DCE liver toxicity by affecting protein glycosylation processes and impairing glycolipoprotein secretion, with a concomitant retention at the level of the Golgi apparatus.     

Vestibular surgical access to the palatine root of the superior first molar: "low-dose cone-beam" CT analysis of the pathway and its anatomic variations

Apicoectomy of the superior first molar palatine root until recently involved relatively destructive and laborious surgery because of the palatal access route, which not only necessitates an extensive flap, but also the readying of procedures required to deal with a possible hemorrhage from the palatine artery. With the advent of operative microscopy, endodontic surgery has become more precise and less invasive and its technical potential has increased; a possible innovative surgical technique may entail vestibular root access. The possibility of using low-dose, low-cost computed tomography (CT) dedicated to the jaw to obtain anatomic information to plan apicoectomy via the vestibular approach was evaluated; 31 patients were referred to CT with the NewTom apparatus. In 43 superior first molars, the mean distance of the palatine root from the external vestibular cortex was measured, and the frequency that the maxillary sinus lateral recess lay between the roots was determined. The mean root apex-vestibular cortex distance was 9.73 mm. In 25% of cases the maxillary sinus recessus lay between vestibular and palatine roots. CT may play an important role in optimizing palatine root apicoectomy through vestibular access, with regard to precision and preventing complications, with relatively low biological and economic cost, also possibly contributing to the affirmation of this new surgical procedure.     

Chronic transmural atrial ablation by using bipolar radiofrequency energy on the beating heart

BACKGROUND: Recently, there has been renewed interest in the development of minimally invasive procedures to treat atrial fibrillation. Unipolar radiofrequency catheters are plagued by poor results, in part because of their inability to produce transmural lesions. This study tested the ability of bipolar radiofrequency energy to create chronic transmural lesions on the beating heart that isolated atrial myocardium. METHODS: Five sheep underwent a right thoracotomy. Baseline pacing was performed from the following targeted areas: right atrial appendage, superior vena cava, inferior vena cava, and right pulmonary veins. A cuff of atrial myocardium around the targeted tissue was clamped between the 2 arms of the device. Radiofrequency energy was delivered at 750 mA and continued until the tissue conductance between the electrodes reached a stable minimum level. After ablation, pacing was used to document tissue isolation. The animals survived for 30 days. RESULTS: Twenty circumferential lesions were produced at the initial operation. The mean ablation time was 9.3 +/- 4.0 seconds, and the mean peak temperature was 48.4 degrees C +/- 6.4 degrees C. All lesions acutely and chronically isolated the targeted tissue. Trichrome staining showed that all lesions were transmural. There were no instances of pulmonary vein stenosis or thrombosis. CONCLUSIONS: Bipolar radiofrequency energy can produce permanent transmural linear lesions on the beating heart. Online measurement of tissue conductance reliably predicted lesion transmurality. This new technology may enable surgeons to perform a curative minimally invasive operation for atrial fibrillation on the beating heart.     

Further evidence of the validity and reliability of the Skindex-29: an Italian study on 2,242 dermatological outpatients

BACKGROUND: Quality of life is increasingly recognized as an important measure in dermatology. The Skindex-29 is a self-administered questionnaire recently developed to measure comprehensively the complex effects of skin diseases on patients' quality of life. OBJECTIVE: We aimed to provide further evidence of the reliability and validity of the Skindex-29 in a large sample of patients affected by a wide variety of skin diseases. METHODS: An Italian version of the Skindex-29 was produced following accepted guidelines for the cross-cultural adaptation of questionnaires. All adult outpatients attending a dermatological hospital on predetermined days were given the Skindex-29 and the 12-item General Health Questionnaire (GHQ-12). RESULTS: A total of 2,242 complete questionnaires were analyzed. The internal consistency and test-retest reliability of each scale were high. The factor structure of the Skindex-29 was strikingly similar to the one originally observed in American patients. The pattern of correlation with the GHQ-12 provided evidence of convergent validity of the Skindex-29. CONCLUSION: The instrument seems to measure three fundamental dimensions of skin health-related quality of life.