Receptor editing in self-reactive bone marrow B cells

A central paradigm of immunology is clonal selection: lymphocytes displaying clonally distributed antigen receptors are generated and subsequently selected by antigen for growth or elimination. Here we show that in mice transgenic for anti-H-2Kk,b antibody genes, in which a homogeneous clone of developing B cells can be analyzed for the outcome of autoantigen encounter, surface immunoglobulin M+/idiotype+ immature B cells binding to self-antigens in the bone marrow are induced to alter the specificity of their antigen receptors. Transgenic bone marrow B cells encountering membrane-bound Kb or Kk proteins modify their receptors by expressing the V(D)J recombinase activator genes and assembling endogenously encoded immunoglobulin light chain variable genes. This (auto)antigen-directed change in the specificity of newly generated lymphocytes is termed receptor editing.     

Treatment of essential arterial hypertension with hypercholesterolemia. Effects of an alpha-adrenergic blocker and an inhibitor of the angiotensin converting enzyme

BACKGROUND: Hypertension and hypercholesterolemia are frequently associated with this leading to considerable cardiovascular risk. METHODS: An open parallel randomized study was performed in which the effects of doxazosin, an alpha-adrenergic blocker and enalapril, an inhibitor of the angiotensin converting enzyme were compared in 70 patients with essential high blood pressure and plasma cholesterol levels greater than 240 mg/dl. Following 2-4 weeks of placebo administration the patients were randomly treated with one of the two drugs. When required doses were increased and hydrochlorothiazide added until blood pressure lower than 160/95 mmHg was achieved. After this period the patients were observed for a minimum of 8 weeks. The mean length of the study was of 22 weeks. RESULTS: Both drugs significantly reduced blood pressure without modifying cardiac frequency. Doxazosin tended to favorably modify the lipid profile of the plasma while enalapril significantly reduced the levels of cholesterol, lipids and high density lipoproteins (HDL). Upon termination of the study the total HDL/cholesterol index increased 8.6% in those treated with doxazosin and decreased 5.5% in those receiving enalapril (p < 0.05). CONCLUSIONS: Although doxazosin and enalapril are potent antihypertensive drugs, the effects on plasma lipid obtained with doxazosin indicate that a reduction in cardiovascular risk was achieved with this drug in the patients included in this study.     

Interleukin 8 (IL-8) induces the expression of kinin B1 receptor in human lung fibroblasts

Near-haploidy is a rare cytogenetic finding in childhood acute lymphoblastic leukaemia (ALL) and is associated with a poor prognosis. A second hyperdiploid line, occurring presumably by endoreduplication of the near-haploid stemline, is often observed. We present a case of common ALL in relapse characterized morphologically by a dual population of small and large lymphoblasts. Cytogenetic analysis supplemented with fluorescence in-situ hybridization (FISH) studies localized near-haploidy and hyperdiploidy to the small and large blast population respectively. DNA ploidy determination confirmed two abnormal clones with near-haploidy as the predominant one. A novel t(9;12)(q11;q13) was present in the near-haploid clone and was duplicated in the hyperdiploid clone. This finding identified cells bearing near-haploidy to be the clonogenic population following malignant transformation and confirmed endoreduplication as the mechanism for the presence of associated hyperdiploidy.     

Study of 18-cm long single-sided AC-coupled silicon microstripdetectors

The SSC GEM silicon Central Tracker design incorporated 18-cm long single-sided AC-coupled silicon microstrip ladders. Compared to the 12-cm long ladders considered in the preliminary stages of the tracker design, the 18-cm long ladders have the advantage of reduced cost, channel count and overall power consumption, and led to a simplified tracker assembly. However, such long ships also present the challenge of maintaining satisfactory performance. The increased capacitance and series resistance contribute to lower signal-to-noise ratios, longer time walk, higher power consumption per channel and increased probability of crosstalk to neighboring channels. In this paper, an accurate method to calculate the geometric capacitance of the AC-coupled microstrips is presented and the calculated results are compared with measurements, SPICE simulations are performed to predict the noise, the extent of interstrip capacitive coupling and the dispersion of the detector signal due to the finite series resistance of the metal strips and the long length of the detector. The influence of the preamplifier current and the shaping time on the signal and noise levels is also presented. The study concludes that the 18-cm long ladders can successfully satisfy the performance goals of the GEM silicon Central Tracker     

The liberal ophthalmologists of the northern France and management of children with vision deficiencies

PURPOSE: The purpose of this analysis was to appreciate the management of visually handicaped children outside specialized structures. We also assessed relays between primary physicians, hospitals and specialized structures. METHOD: A 12-question survey was sent to 144 liberal ophthalmologists of the North of France. The questionnary included 12 questions. We compared the results to litterature. RESULTS: The response-rate was 59.6%. This study indicated that the observed children by the liberal ophtalmologists had more simple diseases than in specialized structures. In hospitals, it seemed that the ophtalmologists diagnosed more severe diseases. These practitioners diagnosed some of these diseases. However some of diagnosis were to late. This study showed that specialized structures were not enough known by the practitioners who detected this handicap and that the families prefered the taking in charge near their home. CONCLUSION: We demonstrated the necessary organisation of precocious and systematic detection, and the necessary information to all practitioners on specialized structures.     

Retrospective analysis of operative ankle fractures

A seroprevalence survey to recently proposed adenovirus (AV) serotypes AV 48 and AV 49, isolated primarily from AIDS patients, was conducted among the San Francisco Men's Health Study cohort. This cohort of homosexual, heterosexual, or bisexual HIV-seronegative and -seropositive men from selected San Francisco census tracts has been studied since 1984. The presence or absence of type-specific antibody in 628 serum specimens from 1989 was determined by microneutralization. Thirty of these subjects (26 positive and four negative) were studied longitudinally. Serum specimens taken at 6-month intervals from 1984 to 1993 were tested to characterize antibody response and to document the advent of these new serotypes. Eight subjects were tested against five other AV serotypes for comparison. AV 48 and AV 49 seroprevalence rates were significantly higher in HIV-seropositives, but infection was not limited to the immunocompromised. Sexual preference was not a significant determinant for AV seroprevalence in HIV-seronegatives. However, the extent and duration of the neutralizing antibody response was strikingly different between homosexuals and heterosexuals: an endemic pattern of continuous reexposure over the 9-year period was seen in 90% of 19 homosexuals, while five of six heterosexuals (83%) had an episodic pattern of exposure with antibody decline to undetectable levels. These data suggest that these viruses may be endemic in some part of the homosexual population and that sexual transmission may be the primary source of continuous reexposure.     

Endometrial cancer: total simple hysterectomy or radical hysterectomy? Abdominal or vaginal route?

Total abdominal hysterectomy and bilateral salpingo-oophorectomy has long been the standard surgical treatment for endometrial cancer. Radical hysterectomy is not useful in stage I. in women with extreme obesity and medical risk factors, vaginal hysterectomy is recommended. Laparoscopy-assisted vaginal hysterectomy complete the oncologic treatment if lymphadenectomy is necessary.     

Exchange and oxidation of CO on O-predosed Rh---Al2O3 and Rh---CeO2 catalysts

Exchange and oxidation of C¹⁶O were investigated at 450°C on ¹⁸O-predosed Rh and Pt catalysts supported on A1₂O₃, CeO₂ and CeO₂-Al₂O₃. In all cases, a rapid exchange of C¹⁶O with the surface can be observed. CO oxidation leads to C¹⁶O₂, C¹⁶O¹⁸O and C¹⁸O₂. Significant formation of C¹⁶O₂ is due to the relatively high ¹⁶O coverage in reaction resulting from the C¹⁶O exchange and from an exchange between O surface species and ¹⁶O internal atoms. Hydrogen is also formed via a water-gas shift reaction (CO + surface OH) in higher proportion on CeO₂-containing catalysts than on A1₂O₃. Chlorine inhibits all the reactions (exchange, oxidation and WGS) and particularly the internal exchange.     

Multiterminal light-emitting logic device electricallyreprogrammable between OR and NAND functions

A monolithic multiterminal logic device that functions both optically and electrically as an ORNAND gate, is demonstrated for the first time. The device, based on the real-space transfer of hot electrons into a complementary collector layer, has been implemented in an InGaAs/InAlAs/InGaAs heterostructure grown by molecular beam epitaxy. Excellent performance is obtained at room temperature. The collector current and the optical output power both exhibit the OR and the NAND functions of any two of the three input terminals, these functions being interchangeable by the voltage on the third terminal     

Crystal structure of tRNA-guanine transglycosylase: RNA modification by base exchange

tRNA-guanine transglycosylases (TGT) are enzymes involved in the modification of the anticodon of tRNAs specific for Asn, Asp, His and Tyr, leading to the replacement of guanine-34 at the wobble position by the hypermodified base queuine. In prokaryotes TGT catalyzes the exchange of guanine-34 with the queuine (.)precursor 7-aminomethyl-7-deazaguanine (preQ1). The crystal structure of TGT from Zymomonas mobilis was solved by multiple isomorphous replacement and refined to a crystallographic R-factor of 19% at 1.85 angstrom resolution. The structure consists of an irregular (beta/alpha)8-barrel with a tightly attached C-terminal zinc-containing subdomain. The packing of the subdomain against the barrel is mediated by an alpha-helix, located close to the C-terminus, which displaces the eighth helix of the barrel. The structure of TGT in complex with preQ1 suggests a binding mode for tRNA where the phosphate backbone interacts with the zinc subdomain and the U33G34U35 sequence is recognized by the barrel. This model for tRNA binding is consistent with a base exchange mechanism involving a covalent tRNA-enzyme intermediate. This structure is the first example of a (beta/alpha)-barrel protein interacting specifically with a nucleic acid.