The organization and animal-vegetal asymmetry of cytokeratin filaments in stage VI Xenopus oocytes is dependent upon F-actin and microtubules

Confocal immunofluorescence microscopy with anti-cytokeratin antibodies revealed a continuous and polarized network of cytokeratin (CK) filaments in the cortex of stage VI Xenopus oocytes. In the animal cortex, CK filaments formed a dense meshwork that both was thicker and exhibited a finer mesh than the network of CK filaments previously observed in the vegetal cortex (Klymkowsky et al., 1987). CK filaments first appeared in association with germinal vesicle (GV) and mitochondrial mass (MM) of oocytes in early mid stage I, indicating that CK filaments are the last of the three cytoskeletal networks to be assembled. By late stage I, CK filaments formed complex networks surrounding the GV, surrounding and penetrating the MM, and linking these networks to a meshwork of CK filaments in the oocyte cortex. During stage III-early IV, CK filaments formed a highly interconnected, apparently unpolarized, radial array linking the perinuclear and cortical CK filament networks. Polarization of the CK filament network was observed during mid stage IV-stage V, as first the animal, then the vegetal CK filament networks adopted the organization characteristic of stage VI oocytes. Treatment of stage VI oocytes with cytochalasin B disrupted the organization of both cortical and cytoplasmic CK filaments, releasing CK filaments from the oocyte cortex and inducing formation of numerous cytoplasmic CK filament aggregates. CB also disrupted the organization of cytoplasmic microtubules (MTs) in stage VI oocytes. Disassembly of oocyte MTs with nocodazole resulted in loss of the characteristic A-V polarity of the cortical CK filament network. In contrast, disruption of cytoplasmic CK filaments by microinjection of anti-CK antibodies had no apparent effect on cytoplasmic or MT organization. We propose a model in which the organization and polarization of the cortical network of CK filaments in stage VI Xenopus oocytes are dependent upon a hierarchy of interactions with actin filaments and microtubules.     

Two reconstructive techniques for flatfoot deformity comparing contact characteristics of the hindfoot joints

The effect of two different methods of reconstruction of flatfoot deformity and the role of the posterior tibial tendon on the contact characteristics of the hindfoot joints were quantified using pressure-sensitive film. Each of 10 cadaver feet was loaded quasi-statically by an axial compressive force to simulate varying loads. First, a specimen was tested intact, then it was tested after sectioning the spring ligament and loading the specimen cyclically to create one type of flatfoot deformity. It was then tested again after reconstructing the deformity. Reconstructions used were the Dillwyn-Evans procedure (bone graft in osteotomy of the calcaneus) or the calcaneocuboid distraction arthrodesis (CCDA). We found that surgically produced flatfoot deformity altered mainly the talonavicular joint, by decreasing its contact area. The Dillwyn-Evans method had less effect on the talonavicular joint (altering 2 of 6 measured parameters) than the CCDA (3 of 6) and more effect on the anteriomedial facet (altering 3 of 6 parameters) than the CCDA (1 of 6). The Dillwyn-Evans method had more effect on the posterior facet (altering 2 of 6 measured parameters) than the CCDA (1 of 6). Function of the posterior tibial tendon had no effect on contact characteristics of the hindfoot joints after either type of reconstruction. These findings are based on measurements using a quasi-statically-loaded foot model at three selected positions, and results may be different with dynamic loading.     

Coupling protein stability and protein function in Escherichia coli CspA

Idiopathic thrombocytopenic purpura (ITP, also known as immune thrombocytopenic purpura) in adults is principally a disease of young women. Although in some patients the onset is acute and complete resolution occurs, in most patients, the onset is insidious and the course is chronic. In spite of the relative frequency of ITP, there are important unresolved issues in its diagnosis and management. For this reason, the American Society of Hematology (ASH) chose ITP as the disease topic for its initial sponsored practice guideline in 1993. A major conclusion of the published guideline was the lack of firm evidence on which to base diagnostic procedures and management strategies. This review describes the clinical features of ITP in adults, emphasizes the principal unresolved issues in diagnosis and management, and outlines the critical areas for future research.     

Effect of altering the daily herbage allowance to cows in mid lactation on the composition, ripening and functionality of low-moisture, part-skim Mozzarella cheese

A retrospective chart review was used to examine sexual behavior (hypersexual, exposing, and victimizing) and cognitive impairment in 200 youth who had serious mental illness. Lower IQ was associated with increased sexual acting-out. For more serious victimizing sexual behaviors, only Verbal IQ differences reached statistical significance. Overall, sexual behavior was strongly associated with a history of sexual abuse. Sexual abuse history was significantly associated only with lower Performance IQ. Therefore, the association between low Verbal IQ and sexual victimizing behavior is distinct from the effects of sexual abuse. Results underscore the importance of verbal cognitive abilities, regardless of overall cognitive level, in the etiology and treatment of sexual behaviors, especially among individuals without a history of sexual abuse.     

Treatment of early T1 small T2N breast cancers. Our experience at the Yaounde General Hospital. 21 cases]

OBJECTIVE: To modify the classic fetal biophysical profile (FBP) with the aim of obtaining rapid and accurate information about actual fetal condition in non-compromised fetuses with a subsequent favorable outcome and to be suitable for a number of outclinic patients. METHODS: Four-hundred and ninety-four fetuses from singleton pregnancies in two randomized groups were monitored by the modified FBP (mFBP) and 168 of them after the external vibratory acoustic stimulation (VAS/mFBP). The mFBP was characterized by two main characteristics: non-stress test was excluded and the testing was finished at the moment when all of the three fetal biophysical activities became normal. The external VAS was applied only in cases with no evidence of fetal activity at the start of the FBP. RESULTS: Of the examined fetuses, 326 fetuses in the control group were monitored by the mFBP and there were 316 (96.9%) favorable outcomes and 10 (3.1%) adverse perinatal outcomes. The sensitivity, specificity and positive and negative predictive values of the mFBP score in predicting adverse perinatal outcome were 60, 99, 66.7 and 98.7%, respectively. In the study group of 168 fetuses there were 165 (98.2%) favorable outcomes and three (1.8%) adverse perinatal outcomes. The sensitivity, specificity and positive and negative predictive values of the VAS/mFBP were 66.7, 100, 100 and 99.4%, respectively. The efficiency of the VAS/mFBP in predicting perinatal mortality alone was even higher. After the external VAS and the first 5 min of the modified testing approximately two-fifths (41.8%) of healthy fetuses with a subsequent good outcome exhibited normal in all of the three biophysical activities and approximately two-thirds (65.5%) of them after 10 min. In the VAS/mFBP group of healthy fetuses, during the same time periods, normal breathing movements were observed in 72% and 87% of fetuses, respectively. CONCLUSIONS: According to our results the mFBP and particularly the VAS/mFBP antenatal protocol as a new and rational variant of the FBP could improve fetal assessment allowing in cases of non-compromised fetuses rapid and accurate information about actual fetal well-being. Because of its high accuracy and a reduced testing time the antepartal method with observation of fetal breathing movements after VAS is becoming acceptable as a screening of fetal well-being evaluation in outclinic conditions.     

Utility of a nitric oxide electrode for monitoring the administration of nitric oxide in biologic systems

Von Hippel-Lindau (VHL) disease is an inherited autosomal dominant neoplastic disorder causing central nervous system haemangioblastomas. The VHL gene (3p25-3p26) is known to be a tumour suppressor gene, with its inactivation being responsible for a predisposition to tumour development. As far as we know, the present report of VHL disease manifestation in identical twins is unique. Genetic inquiry into the family background did not reveal this disease among their progenitors. For presymptomatic diagnosis of 17 presently unaffected family members, constitutional DNA of the twins was screened for VHL germline mutations, using loss of heterozygosity studies and exon-specific DNA sequencing. To determine the influence of somatic mutations of the VHL gene in tumourigenesis, DNA of five surgically removed intracerebral haemangioblastomas of the identical twins was analyzed in comparison with their constitutional DNA by DNA sequencing of the complete VHL coding region. However, no allelic losses were found for the VHL gene or for various other tumour suppressor genes (p53, BRCA1, BRCA2, DCC, and MCC). Furthermore, no mutations were found in the constitutional DNA of either twin sister or in the DNA of all five tumour lesions. Based on our observations, we conclude that in certain VHL families, presymptomatic molecular diagnosis of the disease is not feasible and requires close clinical surveillance of all individuals at risk.     

Comparison of CT and MR imaging in staging of neck metastases

OBJECTIVE: To determine whether adaptive cytoprotection exists in human intestinal cells under in vitro conditions and what role, if any, endogenous prostaglandins or calcium may play in mediating this protective response. SUMMARY BACKGROUND DATA: Adaptive cytoprotection can be defined as that process whereby the administration of a low concentration of a damaging agent, termed a "mild irritant," which by itself is not injurious, can attenuate gastrointestinal mucosal injury subsequently induced by the application of higher concentrations of the same or other necrotizing agents. Despite substantial investigation, the mediator or mediators of adaptive cytoprotection remain poorly understood. METHODS: Postconfluent Caco-2 cells were used in all experiments. Cellular death was quantitated using a dual-component fluorescent assay. Changes in intracellular calcium concentration were quantitated by measuring fluorescent signal changes of the single wavelength calcium indicator (Fluo-3). Finally, prostaglandin E2 release into the media was quantitated by radioimmunoassay. RESULTS: Pretreatment of Caco-2 cells with low concentrations of ethanol (mild irritant) significantly attenuated injury induced by higher damaging concentrations of ethanol. The protection conferred by the mild irritant was directly dependent on both the concentration of the irritant used and the duration of exposure and was abrogated when cells were pretreated with an endogenous prostaglandin inhibitor (indomethacin) or if the mild irritant was administered in calcium-free media. Cells exposed to ethanol had a significant and concentration-dependent increase in intracellular calcium concentration, an effect that was highly related to cellular injury. Pretreatment with a mild irritant significantly decreased intracellular calcium increases induced by not only ethanol but also by a calcium ionophore (A23187). Cells treated with low concentrations of ethanol demonstrated no significant elevation in prostaglandin E2 release. CONCLUSIONS: Adaptive cytoprotection induced by ethanol exists in human colonocytes under in vitro conditions independent of mucosal blood flow, neural innervation, or circulating humoral factors. The authors' data suggest that this response does not require endogenous prostaglandin synthesis but may involve processes whereby intracellular calcium accumulation is prevented.     

The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study

1. We have studied the effects of muscarinic cholinoceptor agonists and subtype-preferring antagonists on the isometric contraction of smooth muscle strips from dog prostate. 2. Acetylcholine and carbachol induced contraction of prostate strips from the peripheral zone, ('the capsule'). Bethanechol contracted the tissue but not at lower doses. McN-A-343 and oxotremorine-M showed the same effects. 3. Blocking alpha- and beta-adrenoceptors with phentolamine and propranolol, respectively, did not modify carbachol-induced contractions. 4. The nicotinic receptor blocker, hexamethonium (10(-6)-10(-4) M) did not affect the contractile response evoked by a single dose of carbachol (10(-5) M), whilst the muscarinic receptor antagonist, atropine (10(-11)-10(-9) M), inhibited it in a competitive manner. 5. The muscarinic M1 (pirenzepine), M2 [AF-DX 116, himbacine (M2/M4) and methoctramine], M3 (HHSID and f-F-HHSID), and putative M4 (tropicamide) antagonists reduced significantly the carbachol-induced contractions. The pIC50 values were: atropine (10.01) > himbacine (8.3) > methoctramine (7.85) > AF-DX 116 (7.60) > HHSID (7.21) > p-F-HHSID (7.10) > pirenzepine (7.30) > tropicamide (7.00). 6. The antagonist profile indicates that an predominant M2 receptor subtype could mediate the muscarinic contraction in the canine prostate.     

The RSNA-AUR-ARRS introduction to research program for 2nd year radiology residents: effect on career choice and early academic performance. Radiological Society of North America. Association of University Radiologists. American Roentgen Ray Society

STUDY OBJECTIVE: To determine whether quantitative measurement of end-tidal carbon dioxide (ETCO2) can differentiate between cardiac and obstructive causes of respiratory distress. DESIGN: Prospective observational study. SETTING: Emergency department (ED) of a tertiary care hospital. PATIENTS: Adult patients who presented to the ED with moderate-to-severe dyspnea. Patients were excluded if they were unable to cooperate with the performance of peak expiratory flow rate (PEFR) or ETCO2 tests, were younger than 18 years of age, or had received prehospital intervention for their respiratory distress. INTERVENTIONS: Physicians obtained an ETCO2 level and PEFR prior to ED pharmacologic intervention. A hand-held capnometer with digital read-out was used to obtain the ETCO2 level. The patient's age, sex, initial vital signs, breath sounds and medication history, the presence or absence of diaphoresis and/or orthopnea, the duration of symptoms, the chest radiograph interpretation, and final diagnosis were also recorded. MEASUREMENTS and RESULTS: Forty-two patients were eligible for inclusion in the analysis. The mean ETCO2 level was 31.1+/-9.4 mm Hg; the mean PEFR was 161.3+/-53.1 L/min. The ETCO2 levels for pulmonary edema/congestive heart failure (CHF) patients differed significantly from those of asthma/COPD patients (27.1+/-7.8 mm Hg vs 33.4+/-9.6 mm Hg; p=0.0375). However, no single ETCO2 level was found to be a reliable predictor of diagnosis. CONCLUSION: ETCO2 levels for pulmonary edema/CHF patients differ significantly from those of asthma/COPD patients. However, no single ETCO2 level reliably differentiates between the two disease processes.     

Reproducibility of right and left ventricular volume measurements by electron-beam CT in patients with congestive heart failure

OBJECTIVE: To assess the efficacy of ultrasound (US) as part of an algorithm to establish the indication for laparotomy in patients with suspected acute appendicitis. DESIGN: Prospective investigation. SETTING: University department of surgery, Germany. SUBJECTS: 669 unselected patients admitted with suspected acute appendicitis. INTERVENTIONS: Clinicopathological and procedural diagnoses of the algorithm were evaluated by correlating clinical and US findings with the results of laparotomy in 171 patients of whom 143 had acute appendicitis (prevalence 21%), and clinical as well as follow up data in the remainder. MAIN OUTCOME MEASURES: The major clinicopathological variables were accuracy and positive predictive value; the rate of negative laparotomies and that of bad diagnostic errors served as the main procedural variables. RESULTS: The overall sensitivity, specificity, and accuracy of the clinical diagnosis were 0.503, 0.950, and 0.855, respectively (positive predictive value: PPV 0.734, negative predictive value: NPV 0.875), those of ultrasound: 0.797, 0.967, and 0.931 (PPV 0.870, NPV 0.946); and 0.853, 0.927, and 0.940 at the end of the algorithm (PPV 0.762, NPV 0.958). However, the algorithm would have resulted in a significant increase in the rate of unnecessary laparotomies (from 13% to 16%). A revised clinical algorithm gave an overall diagnostic accuracy of 0.940 (p < 0.001) together with a low rate of negative laparotomies (11%, p < 0.01) and a significantly reduced number of diagnostic errors (from 71 to 21, p < 0.001). CONCLUSION: Ultrasonography enabled us to diagnose acute appendicitis in more patients more often and more quickly than clinical evaluation alone, suggesting that US may produce a better outcome. The revised clinical algorithm may be helpful in the study of US in patients with suspected acute appendicitis in prospective randomised controlled clinical trials.