Trp82 and Tyr332 are involved in two quaternary ammonium binding domains of human butyrylcholinesterase as revealed by photoaffinity labeling with [3H]DDF

Purified butyrylcholinesterase (BuChE) was photolabeled by [3H]-p-N, N-dimethylamino benzene diazonium ([3H]DDF) to identify the quaternary ammonium binding sites on this protein [Ehret-Sabatier, L. , Schalk, I., Goeldner, M., and Hirth, C. (1992) Eur. J. Biochem. 203, 475-481]. The covalent photoincorporation occurs with a stoichiometry of one mole of probe per mole of inactivated site and could be fully prevented by several cholinergic inhibitors such as tacrine or tetramethylammonium. After complete deglycosylation of the enzyme using N-glycosidase F, the alkylated protein was trypsinolyzed and the digests were analyzed by HPLC coupled to ES-MS. A direct comparison of tryptic fragments from labeled and unlabeled BuChE allowed us to identify the tryptic peptide Tyr61-Lys103 as carrying the probe. Purification of the labeled peptides by anion-exchange chromatography gave a major radioactive peak which was further fractionated by reversed-phase HPLC leading to three, well-resolved, radioactive peaks. Microsequencing revealed that two of these peaks contained an overlapping sequence starting at Tyr61, while the third peak contained a sequence extending from Thr315. Radioactive signals could be unambiguously attributed to positions corresponding to residues Trp82 and Tyr332. This labeling study establishes the existence of two different binding domains for quaternary ammonium in BuChE and exemplifies additional cation/pi interactions in cholinergic proteins. This work strongly supports the existence of a peripheral anionic site in BuChE, implying residue Tyr332 as a key element.     

Discrete Voronoi diagrams and the SKIZ operator: a dynamicalgorithm

The Voronoi diagram (VD) is a popular tool for partitioning the support of an image. An algorithm is presented for constructing VD when the seed set, which determines the Voronoi regions, can be modified by adding and removing seeds. The number of pixels and seeds revisited for updating the diagram and the neighbor relationships among seeds is minimized. A result on cocircular seeds is presented. The adjacency, or dual, graph of the VD is readily obtained. The use of the algorithm for constructing skeletons by influence zones (SKIZ) is demonstrated     

CSDL: a language for cooperative systems design

The aim of a cooperative system is to coordinate and support group activities. Cooperative Systems Design Language (CSDL) is an experimental language designed to support the development of cooperative systems from specification to implementation. In CSDL, a system is defined as a collection of reusable entities implementing floor control disciplines and shared workspaces. CSDL tries to address the difficulties of integrating different aspects of cooperative systems: cooperation control, communication, and system modularization. This paper presents CSDL as a specification language. Basic units are coordinators that can be combined hierarchically. A coordinator is composed of a specification, a body, and a context. The specification defines the cooperation policy; the body controls the underlying communication channels; and the context defines coordinators' interaction in modular systems     

Testicular lymphoma: a population-based study of incidence, clinicopathological correlations and prognosis. The Danish Lymphoma Study Group, LYFO

In a Danish population-based non-Hodgkin's lymphoma registry, 2687 newly diagnosed patients were registered from 1983 to 1992. 39 had testicular involvement (TL) (incidence 0.26/10(5)/year). Median age was 71 years. 24 cases had localised and 15 had disseminated disease. Histologically, all cases were diffuse (65% diffuse centroblastic type). Of the 27 tested, 11% were of T- and 89% of B-immunophenotype. In localised cases, where surgery was supplemented by combination chemotherapy (CCT), the relapse rate was 15.4%. The relapse rate for cases with localised disease treated with other regimens (orchiectomy and/or radiotherapy) was 63.6% (P < 0.05). Median relapse-free survival was 28 and 14 months, respectively. Overall 5-year survival for all cases was 17%. Adverse prognostic factors at the univariate level were stage IV, constitutional symptoms, serum lactic dehydrogenase elevation and performance score (WHO 3-4). It is suggested that the treatment of stage IE/IIE TL should include early CCT and CNS prophylaxis.     

Adult height in girls with idiopathic true precocious puberty

GnRH analogs are used to suppress pituitary-gonadal activity in children with true precocious puberty. The indications for therapy in this situation are not established, as some girls have a slow evolutive form, and the capacity of GnRH analogs to preserve the adult height has not been evaluated. This study analyzes the growth and adult heights of 2 groups of girls with idiopathic true precocious puberty, 1 with a predicted height of 155 cm or less (group 1, 19 cases) and the other with a predicted height of more than 155 cm (group 2, 15 cases). Group 1 patients were treated with a long-acting GnRH analog (D-Trp6-GnRH), and group 2 patients were followed without therapy. Group 1 showed greater clinical signs of estrogenization, vaginal maturation index (P < 0.03), plasma estradiol (P < 0.0004), and ratio of LH/FSH peaks (P < 0.01) at the initial evaluation than did group 2. The mean target heights were similar (difference, 0.9 cm). In group 1, the adult height (159 +/- 1.1 cm) was greater than the predicted height before therapy (152 +/- 1.4 cm; P < 0.0001). The difference between the adult height and the predicted height before therapy (mean, 6.5 cm) correlated positively with the bone age advance (P < 0.01), negatively with the predicted height (P < 0.05), and positively with the difference between the target and predicted heights (P < 0.001) before therapy. In group 2, the adult height (162 +/- 1.4 cm) was similar to the predicted height at the initial evaluation (162.5 +/- 1.4 cm). Adult heights correlated with target height in group 1 and with predicted height at the initial evaluation in group 2. In conclusion, some girls with true precocious puberty and poor adult height prediction who are treated with GnRH analog achieve an adult height more comparable to their target height. However, the lack of effect on height in girls with predicted height at the onset of therapy similar to their target height and preservation of the growth potential in the slow evolutive forms suggest that these forms might not require immediate therapy. Careful follow-up before therapy may be a better way of evaluating their natural course.     

Distribution of hepatic glycosaminoglycans during acute schistosomiasis: modulation by IFN gamma treatment

The neuropsychological characteristics of frontal lobe epilepsy have rarely been reported, with neuropsychological indicators usually being related to subjects with other forms of neurological damage. In this study we assessed the performance of 74 subjects with frontal lobe epilepsy (42 with left, 32 with right frontal epileptic foci) on a series of measures thought to be sensitive to frontal lobe dysfunction and compared to 57 subjects with temporal lobe epilepsy (31 with left, 26 with right epileptic foci). The results indicated a number of measures that could be considered sensitive to frontal lobe epileptic dysfunction. However, the pattern of results did not indicate consistent deficits to be associated with frontal lobe epileptic dysfunction. There are a number of unique factors associated with epilepsy that need to be considered, and these may account for the variable pattern of results obtained. In particular, the rapid propagation of frontal lobe seizures both bilaterally and to other cortical regions has to be considered.     

Quality of life of geriatric patients after surgery. VII. Lung tumors

After reviewing the literature on this subject, the authors examine the results of a five-year follow-up in all patients undergoing lung cancer surgery. The results obtained showed that old-age patients (third age) are more numerous than geriatric (fourth age) patients, and males are more frequently affected than females. The most frequent localisation in the series examined was the upper right lobe and the majority of these patients underwent lobectomy, the form of surgery that produced the best results (30.3% alive and well with a Karnofski index as high as 90 in some cases). The authors conclude that when the patient's conditions allow, surgery is advisable in lung cancer in an attempt to improve the patient's quality of life.     

Laser conization guided by endocervical staining with methylene blue

The authors report their experience of the use of a vital stain--methylene blue--as a surgical guide in laser cervical conization for CIN2-CIN3/CIS. During the period 1 October 1991-31 December 1992 a total of 40 laser cervical conizations were performed under local anesthesia using a CO2 laser connected to a microhandpiece and colposcope in patients with exo-endocervical lesions which were histologically positive for CIN2-CIN3/CIS. In 33/40 patients an aqueous solution of 1% methylene blue was introduced preoperatively in the endocervix using a cotton-wool bud with consequent impregnation of the pseudoglandular crypts: laser biopsy was performed along the guidelines of the stain itself. This enabled the direction of resection to be varied: in 3 patients due to an anomalous and eccentric direction of cervical canal; in 10 patients to remove glandular structures surrounding or underneath lesions; in 8 patients following pseudoglandular section to carry out deep vaporization (3 patients) or correct cutting edges (5 patients). The apex and edges of the cone were always intact. Fourteen patients completed a 12-month follow-up and a further 6 were followed up for 9 months; only 1/14 patients (with AIDS) showed recidivation after 1 year. In the authors' experience the use of a vital stain as a guide during laser cervical cone biopsy is an easily used method which ensures the greatest possible respect for healthy cervical structures, also in order to preserve fertility in young patients.