SURF1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome

A drug with cationic characteristics such as procaine can be conveyed in a Carbomer hydrogel in two different ways: (i) in the form of salt in solution in the aqueous phase, and (ii) in the base form salified with the same polymer. Introduction of the drug into the hydrogel with different concentrations of polymer produced, in both cases, a reduction in viscosity in relation to drug concentration. The gels with procaine salified with the polymer showed greater viscosity. The drug release rate, in general, diminished with the increase in polymer concentration. Nevertheless, when this concentration was maintained, there was no variation in release rate when the viscosity produced as a consequence of drug concentration was changed. Gels with procaine salified with the carboxyvinylic polymer had a faster release rate than those with procaine in the hydrochloride form dissolved in the aqueous phase. These results have also been confirmed by a simulated absorption test.     

Cloning and characterization of a symbiosis-related gene from an ectomycorrhizal fungus Laccaria bicolor

Point-to-point functional movements involve simultaneous shoulder and elbow joint rotations. In able-bodied subjects these movements are fully automatic, and feed-forward control ensures the synergistic activity of many muscles. Synergy between joint rotations was defined and described as a scaling between joint angular velocities [19]. Similarly, subjects who can control their shoulder movements may be assisted in reaching tasks by functional electrical stimulation (FES) of elbow extensor muscles. The synergistic control paradigm can be implemented in real-time by employing a hierarchically structured production-rules method. The use of production-rules necessitates the acquisition of knowledge and the assembly of a rule-base. A nonparametric technique was designed for the identification of the rules. The identification process was divided into two phases: determination of the scaling parameters, and determination of the stimulation parameters. The scaling parameters, needed for the coordination of movements, were determined in able-bodied subjects. Those depend exclusively on the initial and target positions of the hand. The number of scalings could be reduced by dividing the workspace into 12 zones. The stimulation parameters, needed for the execution of movements, were determined in subjects with paralyzed elbow extensor muscles by identifying triplets: elbow angular velocity, elbow angular acceleration (velocity increments), and the corresponding pulse durations for various classes of movements and loads attached to the hand.     

Increased levels of intracellular calcium are not required for the formation of attaching and effacing lesions by enteropathogenic and enterohemorrhagic Escherichia coli

Elevated concentrations of intracellular calcium ([Ca]i) have been implicated as an important signalling event during attaching and effacing (A/E) lesion formation by enteropathogenic Escherichia coli (EPEC). The highly localized nature of the cytoskeletal and cell surface alterations occurring during A/E lesion formation suggests that there should be equally localized EPEC-induced signalling events. To analyze further the calcium responses to infection of HEp-2 cells by EPEC, we employed calcium-imaging fluorescence microscopy, which allows both temporal and spatial measurements of [Ca]i in live cells. Using this imaging technique, not only were we unable to detect any significant elevation in [Ca]i at sites of A/E EPEC adhesion, but, with several different classical EPEC and enterohemorrhagic E. coli (EHEC) strains and three different infection procedures, each of which resulted in extensive A/E bacterial adhesion, we were unable to detect any significant alterations in [Ca]i in infected cells compared to uninfected cells. In addition, chelation of intracellular free calcium with bis-(aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA) did not, as previously reported, prevent A/E lesion formation. We conclude that increased [Ca]i are not required for A/E lesion formation by EPEC and EHEC.     

Differential expression and distribution of focal adhesion and cell adhesion molecules in rat hepatocyte differentiation

The present study has examined the distribution of axons of differing sizes in the optic pathway of the ground squirrel. Axon diameters were measured from electron micrographs at various locations across sections of the optic nerve and tract, and total distributions and numbers were estimated. In both the nerve and tract, roughly 1.2 million optic axons were present. The population of optic axons had a unimodal size distribution, peaking at 0.9 microm in diameter and having an extended tail toward larger diameters. Local axon diameter distributions in the optic tract indicated distinct (though partially overlapping) axon diameter classes, including one of fine sizes peaking at 0.8-0.9 microm, a second of medium sizes peaking around 1.7-1.8 microm, and a third composed of the larger fibers with diameters up to 4.8 microm. The fine-caliber axons were found at all locations in the tract, and were the only axons present immediately adjacent to the pia, while the medium- and coarse-caliber axons were found at deeper locations. Curiously, the larger axons were found primarily in the medial parts of the tract, where axons from the dorsal retina normally course. A similarly restricted distribution of the larger axons was observed in the dorsotemporal parts of the optic nerve, suggesting that this difference in the tract may relate to an asymmetric distribution of ganglion cells on the retina giving rise to these axons. Measurements of axonal size taken within the optic fiber layer in dorsal and ventral parts of the retina confirmed this asymmetry, consistent with previous demonstrations of soma size differences in the dorsal versus ventral retina. The partial segregation of axons by size in the optic tract of the ground squirrel then reflects both the asymmetric distribution of retinal ganglion cell classes and the chronotopic reordering of optic axons that occurs within the chiasmatic region.     

Treatment of acute lymphoblastic leukemia. 30 years' experience at St. Jude Children's Research Hospital

BACKGROUND: Therapy for childhood lymphoblastic leukemia has evolved during the past three decades, but key questions about what are the least toxic, most effective forms of treatment remain unanswered because of the lack of comprehensive follow-up information. METHODS: To assess long-term outcome in the series of clinical trials conducted at St. Jude Hospital, we compared the results of treatment typical of four eras: exploratory combination chemotherapy (era 1, 1962 to 1966; 91 patients), regimens for the control of meningeal leukemia (era 2, 1967 to 1979; 825 patients), limited intensification of therapy (era 3, 1979 to 1983; 428 patients), and extended intensification of therapy (era 4, 1984 to 1988; 358 patients). ("Intensification" refers to strategies of systemic chemotherapy that are more aggressive than conventional ones.) The major end points were survival and event-free survival; we also calculated the relative risk of treatment failure and the rate of relapse or death after treatment ended (post-treatment failure rate). RESULTS: The probability of event-free survival improved significantly in each successive era (P < 0.001 by the log-rank test), reaching 71 percent in era 4. There was a decrease of approximately 50 percent in the risk of treatment failure from one era to the next in each subgroup of patients defined according to different combinations of the leukocyte count, race, age, and sex. Leukemia appeared to be eradicated in patients who remained in complete remission for three years or more after treatment in era 4. The incidence of death due to nonleukemic causes remained 4 to 6 percent despite the trend toward more intensive treatment. An estimated 765 patients (45 percent) are long-term survivors; most of them (80 percent) have no health problems related to leukemia or its treatment. CONCLUSIONS: The development and successful application of preventive therapy for meningeal leukemia, followed by the intensification of systemic chemotherapy, has progressively improved the rate of cure of childhood lymphoblastic leukemia, with relatively few adverse sequelae.     

Effect of set-up error on the dose across the junction of matching cranial-spinal fields in the treatment of medulloblastoma

PURPOSE: The effect of systematic and stochastic setup error on the dose delivered to the gap region for the three field radiation treatment of medulloblastoma is studied. The consequences of such setup error is discussed. METHODS AND MATERIALS: The treatment of medulloblastoma is typically a 3 field technique, in which two lateral cranial fields are matched with a spine field. The x-ray dose delivered to the region between the matched fields depends upon the gap size. The choice of the gap width between the cranial and spinal fields is controversial. It is currently a compromise between minimizing the risk of dose hot spots to the spine, and the associated clinical complications, as well as the magnitude of cold spots (underdosing) across the gap, with the associated risk of disease recurrence. In this paper, we examine the effect of gap width with a moving junction, referred to as "field feathering", on the dose across the field junction for a 6MV photon beam. In addition, we have studied 129 portal films and 40 simulation films to assess the accuracy and precision of patient setup during treatment with a plan involving feathered fields. Selected landmarks observable on both portal and simulation films were identified and the variation in the distances to the field edges measured. The distribution of patient setup error was convoluted with the beam profiles for a 6MV linac. These convoluted field edges were used obtain dose profiles across the gap region as a function of gap separation. The consequences for therapy are discussed. In addition, analysis of patient setup error on an alternative treatment involving beam modifiers to broaden the beam penumbra is discussed. RESULTS: The magnitude of the spatial stochastic and systematic setup error was determined to be approximately three and two millimeters respectively. The dosimetric consequences of patient setup error lead to over and under dosing in the spinal gap region for the three field technique. The degree of under or over dose depends on the nature and magnitude of the patient setup error. CONCLUSIONS: The effect of patient setup error can lead to significant dosimetric errors in the dose to the gap region depending on the magnitude of the setup errors. The effective over and under dose can be compensated by the use beams modifiers such as a beam spoiler or vibrating jaws.     

Detection of extrathoracic metastases by positron emission tomography in lung cancer

BACKGROUND: Accurate staging of non-small cell lung cancer is essential for treatment planning. We evaluated in a prospective study the role of whole-body 2-[18F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in mediastinal nodal staging with a positive predictive value of 96%. The study was continued to further evaluate the value of whole-body FDG PET in detecting unexpected extrathoracic metastases (ETMs) in patients qualifying for surgical treatment by conventional staging. METHODS: One hundred patients underwent clinical evaluation, chest and upper abdominal computed tomography scan, mediastinoscopy (lymph nodes greater than 1 cm on computed tomography), and routine laboratory tests. In 94 patients with stage IIIa or less and 6 with suspected N3 a whole-body FDG PET was performed. If clinical signs of ETMs were present additional diagnostic methods were applied. All findings in the FDG PET were confirmed histologically or radiologically. RESULTS: Unexpected ETMs were detected in 13 (14%) of 94 patients (stage IIIa or less) at 14 sites. In addition 6 of 94 patients were restaged up to N3 after PET. The suspected N3 disease (stage IIIb) on computed tomography was confirmed by PET in all 6 patients. There was no false positive finding of ETM. Weight loss was correlated with the occurrence of ETM: more than 5 kg, 5 of 13 patients (38%); more than 10 kg, 4 of 6 patients (67%). Pathologic laboratory findings were not predictive for ETM. CONCLUSIONS: Whole-body FDG PET improves detection of ETMs in patients with non-small cell lung cancer otherwise elegible for operation. In 14% of patients (stage IIIa or less), ETMs were detected, and in total, 20% of the patients were understaged.     

Functionalized 1,3-teraryls as a new class of hepatoprotectants. Part V

A 29-year-old man was admitted to the hospital because of a high fever and dyspnea. He had a history of bronchial asthma and had had a bullectomy of the right lung at 15 years of age. He had visited a family physician because of fever and non productive coughing. Medications had no effect on his symptoms, and dyspnea developed. A chest X-ray film showed total collapse of the right lung, and he was referred to our hospital. Laboratory data showed eosinophilia and a high titer of IgE. Total obstruction of the right main stem bronchus by mucous plug was found during fiberoptic bronchoscopy. Aspergillus was detected by pathological examination of bronchial lavage fluid. Tests for aspergillus-specific IgE and IgG antibody were positive, as was immediate skin reactivity to Aspergillus. Allergic bronchopulmonary aspergillosis (ABPA) was diagnosed. Infusion and inhalation of a corticosteroid and fluconazole were effective; the symptoms resolved and X-ray findings improved. While migratory infiltration, proximal bronchiectasis and segmental or subsegmental atelectasis caused by a mucous plug are common X-ray findings in allergic bronchopulmonary aspergillosis, total collapse is rare.