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Biomedical subjects

U Weiss

Publications and source records attributed to U Weiss.

At least 55 records · Page 3Linked to original sources

[Movement, play and sports in the treatment of drug addicts].

In 1992 a campaign was initiated to bring to attention new ways for drug prevention in adolescents for health promotion in addicts and for therapy and follow-up of ex-addicts. By this broad base the Swiss Health Authority and the Federal Sports Institute at Magglingen together with partners from Swiss sport and addiction-care organizations try to contribute to a reduction of drug-related problems in Switzerland. The following article bases mainly on experiences with long-term therapy of the 'Drogenhilfe Aebihus' in Leubringen.

Adolescent↗

Bcl-2 increases memory B cell recruitment but does not perturb selection in germinal centers.

To address the role of apoptosis in the humoral immune response, we have examined a well-characterized T cell-dependent B cell response in mice expressing transgenic Bcl-2 in their B lymphocytes. The selection of somatic mutants and the appearance of high affinity antibodies was not affected by constitutive Bcl-2 expression. Such expression did, however, disproportionately increase the antigen-specific memory B cell pool, suggesting that the final size of the memory compartment may be regulated by an apoptotic process, which, in turn, can be influenced by Bcl-2. In addition, transgenic mice showed prolonged survival of foci of early antibody-producing cells, suggesting their removal is mediated by apoptosis that can be blocked by Bcl-2.

Animals↗

[The child, growth and high-level sports].

The hormonal response to a short but intense session of physical exercise should be distinguished from the endocrine adaptation to systematic physical conditioning. The normal child is perfectly equipped to handle stress situations such as those generated by leisure sport: the transient increase in stress hormones has no deleterious effect on growth and puberty. For highly trained children and adolescents, standardized dynamic testing will provide little information on the state of their endocrine system. In addition, the effects of training should be differentiated from those of various bias of selection. In young elite athletes, as for adult athletes, the alterations of the endocrine system result from an inappropriate physical conditioning programme for the individual level of tolerance. Whereas it has been shown that the gonadal function is predominantly affected (pubertal delay, menstrual dysfunction), alterations of growth hormone and cortisol productions have also been reported. Anomalies of pubertal growth should be searched for among elite adolescent athletes: there are data suggesting that their growth potential should probably not be affected below 15 weekly hours of training. However, children do not respond to stress in a uniform manner and one should be prepared to detect the occasional athlete with inadequate growth at lower training intensities. This seems to be the case when training starts before puberty as well as in physical activities associated with a strict weight control. When growth and/or puberal progression become inappropriate, the only logical therapy consists in reducing markedly or stopping training temporarily: in this situation, there is no medical justification whatsoever to initiate a substitutive therapy.

Adolescent↗

Thoracoscopic oesophagectomy with intrathoracal stapled anastomosis.

Techniques for intrathoracal stapler anastomosis under thoracoscopic control were studied and developed in an experimental program. Since this procedure is possible from two directions, both directions were evaluated. Two different techniques, a transoral and a transhiatal, resulted. For the transoral technique the stapler is inserted from above. The anvil, which is connected to a wire, is drawn into the abdomen together with the distal oesophagus. Retracting the wire pulls both the anvil and the stomach tube up into the thorax after the insertion of the anvil. The second technique requires a special attachment to introduce the anvil transhiatally into the thorax and into the oesophageal stump. The gastric tube is pushed into the thorax by the stapler gun, which is inserted into the stomach through an antrostomy. The insertion of the anvil into the oesophageal stump can also be achieved with the support of a flexible endoscope including a polyp snare.

Anastomosis, Surgical↗

Reduction of the disulfide bond of chromogranin B (secretogranin I) in the trans-Golgi network causes its missorting to the constitutive secretory pathways.

The role of the single, highly conserved disulfide bond in chromogranin B (secretogranin I) on the sorting of this regulated secretory protein to secretory granules was investigated in the neuroendocrine cell line PC12. Treatment of PC12 cells with dithiothreitol (DTT), a membrane permeable thiol reducing agent known to prevent disulfide bond formation in intact cells, resulted in the secretion of newly synthesized chromogranin B, but only slightly decreased the intracellular storage of newly synthesized secretogranin II, a regulated secretory protein devoid of cysteines. The secretion of newly synthesized chromogranin B in the presence of DTT occurred with similar kinetics to those of a heparan sulfate proteoglycan, a known marker of the constitutive secretory pathway in PC12 cells. Analysis of the various secretory vesicles derived from the trans-Golgi network (TGN) indicated that DTT treatment diverted newly synthesized chromogranin B to constitutive secretory vesicles, whereas the packaging of secretogranin II into immature secretory granules was unaffected by the reducing agent. The chromogranin B molecules diverted to constitutive secretory vesicles, in contrast to those stored in secretory granules, were found to contain free sulfhydryl residues. The effect of DTT on chromogranin B occurred in the TGN rather than in the endoplasmic reticulum. We conclude that the sorting of CgB in the TGN to secretory granules is dependent upon the integrity of its single disulfide bond.

Animals↗

Evidence for a reduction of growth potential in adolescent female gymnasts.

The goal of this prospective study was to assess whether intensive physical training during puberty could alter the growth potential of adolescent female athletes. Height, sitting height, leg length, weight, body fat, and pubertal stage of 22 gymnasts aged 12.3 +/- 0.2 years (mean +/- SEM), with an average training period of 22 hr/wk, and of 21 swimmers aged 12.3 +/- 0.3 years (average training period 8 hr/wk) were recorded half-yearly for a mean period of 2.35 years (range 2.0 to 3.7 years). Adult height predictions were performed with the methods of Bayley and Pinneau; Roche, Wainer, and Thissen, and Tanner et al. Growth velocity of gymnasts was significantly lower than that of swimmers from 11 to 13 years of bone age (p < 0.05), with a mean peak height velocity of 5.48 +/- 0.32 cm/yr versus 8.0 +/- 0.50 cm/yr for swimmers. Height standard deviation score decreased significantly in gymnasts with time (r = -0.747; p < 0.001). This observation was not associated with a significant alteration of chronologic age/bone age ratio. By contrast, height standard deviation score remained unchanged in swimmers (r = -0.165; p = 0.1). A marked stunting of leg-length growth was observed in gymnasts from 12 years of bone age, resulting in a marked difference in overall sitting-height/leg-length ratio (gymnasts 1.054 +/- 0.005 vs swimmers 1.100 +/- 0.005; p < 0.001). Concomitantly, predicted height of gymnasts decreased significantly with time (Tanner et al.: r = 0.63, p < 0.001; Bayley-Pinneau: r = 0.44, p < 0.001), whereas those of swimmers did not change. We conclude that heavy training in gymnastics (> 18 hr/wk), starting before puberty and maintained throughout puberty, can alter growth rate to such an extent that full adult height will not be reached. The mechanisms underlying these observations are not settled; we suggest that prolonged inhibition of the hypothalamic-pituitary-gonadal axis by exercise, together with or because of the metabolic effects of dieting, is responsible for them.

Adolescent↗

Visually controlled trocar insertion by means of the "optical scalpel".

The importance of a safer approach to the abdominal cavity has led to several developments in the field of trocars, cannulae and puncture techniques. Examples are the insertion of a needle scope into a Veress needle, complex access cannulae and our new principle of using an "optical scalpel". In our view, direct optical visualization and actively controllable penetration of the abdominal wall are mandatory. First experimental and clinical applications indicate the newly developed "optical scalpel" (Olympus Winter & Ibe, Hamburg, Germany) as a reliable and useful instrument for a safe approach to the endoscopic operative field. This instrument was successfully used in 10 endoscopic operations and is currently undergoing further clinical testing.

Abdomen↗

Laparoscopic treatment of common bile duct stones. Phantom experiments using electrohydraulic and pulsed dye laser lithotripsy.

To evaluate the feasibility of laparoscopic transcystic lithotripsy of common bile duct stones, a phantom model comprising bovine liver and biliary tract tissue integrated within a laparoscopic trainer was built. A 9 French cholangioscope was introduced via the cystic duct into the common bile duct in which a human gall stone of known composition had been introduced. Lithotripsy was performed using either a laser or electrohydraulic probe passed through the working channel of the cholangioscope following which the stone fragments were manipulated into the duodenum through the papilla of Vater using the choledochoscope. A total of 20 lithotripsies with each energy form were performed. Lithotripsy was successful in breaking the stones into fragments smaller than 6 mm. The energy expenditure was comparable with a mean of 49 J for laser lithotripsy (range 9 to 159 J), and 53 J (range 16 to 160 J) for electrohydraulic wave lithotripsy. The lithotripsy time measured from introduction of the cholangioscope until its removal was a mean of 30 minutes for electrohydraulic wave lithotripsy and 41 minutes for dye laser lithotripsy. This difference was statistically significant. Macroscopic tissue damage to the common bile duct wall was not observed following any procedure. An additional experiment was performed to evaluate damage that could be caused to the wall of the common bile duct. Both electrohydraulic shock wave and pulsed dye laser lithotripsy without optical feedback regulation caused severe tissue defects when there was tissue contact or distance less than 2 mm. With optical feedback regulation however, no tissue damage was induced by laser lithotripsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Accumulation of somatic mutants in the B cell compartment after primary immunization with a T cell-dependent antigen.

The accumulation of somatic mutants in splenic B lymphocytes early after primary immunization with the hapten (4-hydroxy-3-nitro-phenyl)acetyl (NP) coupled to chicken gamma globulin (CG) was determined. Rearranged V186.2 heavy chain genes were amplified by the polymerase chain reaction from genomic DNA and subjected to nucleotide sequence analysis. Somatic antibody mutants become detectable on day 6 after immunization, and most of the somatic mutations accumulating in the memory compartment are introduced until day 14. At this time strong selection for mutants expressing high binding affinity for NP is apparent. Extrapolation from the mutation frequency increases between day 6 and day 14 to the previously determined mutation frequency at week 6 (Weiss. U. and Rajewsky, K., J. Exp. Med. 1990, 172: 1681) leads to the prediction that the process of mutant generation ceases to operate around day 22 after primary immunization.

Amino Acid Sequence↗

Widespread occurrence of chromogranins/secretogranins in the matrix of secretory granules of endocrinologically silent pituitary adenomas.

To investigate the constituents of the matrix of endocrine secretory granules, we analyzed endocrinoilogically silent ("non-functioning") human pituitary adenomas for the occurrence of the chromogranins/secretogranins (granins), a protein family normally stored together with many different hormones. When five non-functioning pituitary adenomas were analyzed by immunoblotting using polyclonal and monoclonal antibodies specific for individual members of the granin family, chromogranin A was detected in four cases and chromogranin B and secretogranin II were detected in all cases. The cellular distribution of the granins and of various hormones known to be expressed in the anterior pituitary was studied by immunocytochemistry in fixed, frozen tissue sections from five additional adenomas. Of the eight hormones investigated, only thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone were detected, occurring in only two of the five adenomas. In contrast, granins were found in all five tumors. Chromogranin B and secretogranin II were detected in each of the adenomas in virtually every cell studied, whereas chromogranin A exhibited such a widespread cell distribution in only three adenomas, being focally present in one and absent from the other tumor. The subcellular localization of the granins and the three glycoprotein hormones was investigated by double immunoelectron microscopy. Chromogranin A and chromogranin B were mainly co-localized in secretory granules, whereas secretogranin II was either co-localized with the other two granins or segregated to different secretory granules. When present, glycoprotein hormones were immunodetected in both the secretory granules containing all three granins and those containing mainly secretogranin II. Our data indicate that in non-functioning pituitary adenomas chromogranin A is differentially expressed from chromogranin B and secretogranin II. Moreover, the granins appear to be the most widespread constituents of endocrine secretory granules known, forming the dense-core matrix irrespective of the presence or absence of hormones.

Adenoma↗

Intraclonal generation of antibody mutants in germinal centres.

The generation and selection of somatic antibody mutants are key elements of acquired immunity, essential for the affinity maturation of antibody responses dependent on T cells. The mutants are generated through a mechanism that introduces point mutations at high rate into rearranged variable (V) region genes in the course of cell proliferation. Their appearance coincides with the generation of germinal centres, which are characterized by oligoclonal B-cell proliferation and have been suggested to be the microenvironment in which antibody mutants are generated. We report here direct evidence for this hypothesis. Rearranged V-region genes were amplified from the genomic DNA of cells picked from individual germinal centres. The sequence analysis of these genes revealed that most represent cells of distinct B-cell clones which expanded locally, generating somatic antibody mutants at high rate. By contrast, antigen-induced proliferation of B cells at another site, periarteriolar lymphocyte sheath-associated foci, was not associated with somatic hypermutation.

Amino Acid Sequence↗

The repertoire of somatic antibody mutants accumulating in the memory compartment after primary immunization is restricted through affinity maturation and mirrors that expressed in the secondary response.

The anti-(4-hydroxy-3-nitro-phenyl)acetyl (NP) response is dominated by lambda 1 chain-bearing antibodies expressing the VH gene V186.2 in combination with the D element DFL16.1. lambda 1-positive B cells were isolated from the spleens of mice immunized with NP-chicken gamma globulin 6 wk earlier. Rearranged V186.2 genes were amplified from the genomic DNA of these cells and sequenced. In cases where the rearrangement was typical for secondary anti-NP antibodies, the VHDJH sequences were generally heavily mutated. The frequency and the nature of the nucleotide exchanges mirrored those of secondary response antibodies. V186.2 genes with other rearrangements and V186.2-related genes isolated concomitantly were essentially unmutated. These results demonstrate: (a) that somatic antibody mutants are largely restricted to a small compartment of peripheral B cells, namely, that of memory cells; (b) that the memory compartment is strongly selected for high affinity precursors and largely purged from antigen-binding loss mutants; and (c) that the repertoire of binding specificities expressed in the secondary response is established in its final form before secondary immunization.

Amino Acid Sequence↗

Requirement for GTP hydrolysis in the formation of secretory vesicles.

The specificity of vesicular transport in a cell is determined by the formation of vesicles with specific contents from a donor compartment and their selective fusion with the appropriate acceptor compartment. Several of the latter fusion steps have been investigated in detail using cell-free systems, and work with these systems as well as genetic evidence has revealed a role for GTP-binding proteins in membrane fusion processes. We have reconstituted the formation of constitutive secretory vesicles and immature secretory granules from the trans Golgi network in a cell-free system. We show here that the budding of both types of post-Golgi vesicles is inhibited by non-hydrolysable analogues of GTP, which suggests a more widespread role for GTP-binding proteins in membrane traffic than previously assumed.

Animals↗