Heavy chain variable (VH) region diversity generated by VH gene replacement in the progeny of a single precursor cell transformed with a temperature-sensitive mutant of Abelson murine leukemia virus

Sequence analysis of a large number of DNA clones containing a functional heavy chain variable, diversity, and joining (VHDJH) complex generated by VH to VHDJH joining (VH gene replacement) in the progeny derived from a common precursor cell transformed with a temperature-sensitive (ts) Abelson murine leukemia virus (A-MuLV) indicates that endogenous VH gene replacement in vitro generates immunoglobulin gene joints distinct from those generated by the usual VH to DJH joining. Such joints keep the pentamer CAAGA at the 3' end of the donor VH segment and lack a recognizable D segment, as can be seen also in vivo. The results suggest that VH gene replacement participates in generating VH region diversity in vivo, as previously postulated. During the joining process, a unique VH gene was selected in all progeny cells, together with a single A nucleotide dominantly added to the junctional boundaries. The basis of these regulatory processes is discussed.     

Noninvasive hemodynamic assessment of internal thoracic artery grafts using duplex echocardiography from supraclavicular fossa--a comparison with Doppler catheter method

We evaluated the usefulness of noninvasive hemodynamic assessment of internal thoracic artery grafts (ITAGs) using duplex Doppler echocardiography from the supraclavicular fossa (transcutaneous pulsed Doppler method: PD method). Eighteen ITAGs were examined by PD method in comparison with Doppler catheter method using Doppler flowire (DC method). The hemodynamic indices used were the diastolic/systolic peak velocity ratio (DSVR) and the diastolic fraction of time-velocity integral (DF) in the ITAGs. A significant linear correlation was seen both in DSVR and DF between these two methods (p < 0.01). The subjects were assigned to two groups according to angiographic findings Group A (Gr-A: 5 grafts) with string sign including significant graft stenosis and group B (Gr-B 13 grafts) with good patency. In both PD and DC methods, DSVR and DF were significantly lower in Gr-A than in Gr-B (p < 0.01). The blood flow pattern was thus systolic dominant in the grafts with string sign, while it was diastolic dominant in the grafts with good patency. In some grafts in Gr-B, however, both DSVR ad DF were as low as that in Gr-A. Responding to pacing, Gr-B further increased both DSVR and DF, but Gr-A did not. As a result, the difference between both groups was further distinguished. In summary, ITAG function can be assessed by the noninvasive PD method. Interventions such as exercise, dobutamine infusion may make it more accurate, particularly in evaluating borderline data.     

Alcoholic effect on male sexual function

Though an adequate volume of ethanol relieves nervousness and enhances sexual desire, acute administration of a great deal of ethanol suppresses central nervous system and causes sensory torpor and penile erectile dysfunction. Long term and excessive intake of ethanol causes central and/or peripheral neuropathy and sexual dysfunction; atrophy of testicles, low serum level of testosterone, impaired spermatogenesis and penile erectile dysfunction. It also invades various organs in digestive tract, cardiovascular system, central and peripheral nervous system and causes functional disorders in these organs. Successful treatment of patients with penile erectile dysfunction should be performed with treatment of these underlying and associated disease.     

Experimental studies on output, spatial, and spectralcharacteristics of a microdroplet dye laser containing Intralipid as ahighly scattering medium

Lasing characteristics of Rhodamine 6G dye-doped microdroplets containing highly scattering fat emulsion Intralipid-10% are studied experimentally. Noteworthy findings are that well-defined lasing threshold can be observed and one order or more magnitude enhancement of emission intensity with suitable (optimum) conditions of the Intralipid mixing ratio, in comparison with original neat-dye lasing microdroplets. We present and discuss the measured results of input-output intensities for different dye concentrations and dye-Intralipid mixing ratios in this high-gain laser dye-soft scatterer system and microscope images of spatial distribution of light emission from both the microdroplets containing neat-dye and dye-Intralipid mixture. It was found that almost no-lasing neat-dye microdroplets, which have either much higher or much lower dye concentration, can achieve lasing by substituting suitably certain amounts of the Intralipid, causing multiple light scattering. Spectral measurements of lasing outputs from the Rhodamine 6G dye-Intralipid microdroplets show the tendency of the disappearance of the well-known mode structures, owing to the morphology-dependent resonances of this microspherical cavity inherent to the neat-dye microdroplets. It is our belief that the present results make this novel method of dye-Intralipid microsystem very attractive for a variety of future applications, including diagnostic tools for highly sensitive detection and identification of small quantity objects and species embedded or hidden in highly scattering media, such as biological tissues and cellular structures     

Growth inhibition of K-ras-expressing tumours by a new vinca alkaloid, conophylline, in nude mice

Conophylline, a new vinca alkaloid isolated from the plant Ervatamia microphylla induced normal flat morphology in K-ras-NRK and K-ras-NIH cell lines, and lowered the increased uptake of 2-deoxyglucose in K-ras-NRK cells. Conophylline inhibited the growth of K-ras-NRK cells, but this inhibition was reversible. The alkaloid also inhibited the growth of K-ras-NRK and K-ras-NIH3T3 tumours transplanted into nude mice. On the other hand, it showed no effect on survival of the mice loaded with L1210 leukaemia. Thus, conophylline is a new antitumour vinca alkaloid that induced normal phenotypes in ras-expressing cells.     

Significance of a diastolic notch in the uterine artery flow velocity waveform induced by uterine embolisation in the pregnant ewe

OBJECTIVE: To determine whether water exposure causes middle ear contamination in patients with collar button tympanostomy tubes (TTs). METHOD AND DESIGN: An in vitro model of a human head that contained an auricle, external auditory canal, tympanic membrane with TT, middle ear, eustachian tube, and mastoid cavity was developed. Two electrodes connected to an external ohmmeter resided in the middle ear to detect water entry. The model was tested with 4 types of water exposure: showering, bathing, hair rinsing, and swimming. Statistical analysis was performed by the Fisher exact test. MAIN OUTCOME MEASURES: A positive test result corresponded to water entering the middle ear via the TT, confirmed by a resistance reading of zero on the ohmmeter. A negative test result indicated no change in the initial high resistance reading. RESULTS: No positive test results were obtained for showering (0 of 60 tests), hair rinsing (0 of 60 tests), or head submersion (12.7 cm) in clean tap water (0 of 60 tests). Ten positive test results were obtained for head submersion in soapy water (10 of 97 tests), which was statistically different from clean water (P< or =.007). Swimming pool depths of 30, 45, 60, and 75 cm elicited positive test results in 2 of 16, 3 of 18, 2 of 20, and 11 of 20 tests, respectively. A higher incidence of water entry into the middle ear occurred at depths of more than 60 cm (P< or =.001). No statistical difference between depths of 60 cm or less occurred (P= .88). CONCLUSIONS: Showering, hair rinsing, and head submersion in clean tap water do not promote water entry into the middle ear. Submersion in soapy water increases the probability of water contamination. Pool water infrequently enters the middle ear with head submersion, but the incidence increases with deeper swimming (>60 cm). These data provide further evidence that many water precautions frequently advised in patients with TTs are unnecessary.     

A case of chronic pancreatitis complicated by massive pericardial and right pleural effusion

A 42-year-old man was admitted complaining of dyspnea. Chest X-ray showed an increase in cardiac size, and echocardiography revealed a large volume of pericardial effusion. Pancreatic enzyme levels were elevated in both serum and pericardial effusion. Computed tomography and endoscopic retrograde pancreatography demonstrated a fistula connecting a pancreatic pseudocyst with the pericardium and the right pleural cavity. Massive pericardial and right pleural effusion is an extremely rare complication of chronic pancreatitis. In this case, computed tomography and endoscopic retrograde pancreatography were useful for diagnosing the fistula.     

Activation of protein kinase C induces cortical granule exocytosis in a Ca(2+)-independent manner, but not the resumption of cell cycle in porcine eggs

N-Acetylneuraminic acid (1) is a common sugar in many biological recognition processes. Neuraminidase enzymes recognize and cleave terminal sialic acids from cell surfaces. Viral entry into host cells requires neuraminidase activity, thus inhibition of neuraminidase is a useful strategy for development of drugs for viral infections. A recent crystal structure for influenza viral neuraminidase with sialic acid bound shows that the sialic acid is in a boat conformation [Prot Struct Funct Genet 14: 327 (1992)]. Our studies seek to determine if structural pre-organization can be achieved through the use of sialyllactones. Determination of whether siallylactones are pre-organized in a binding conformation requires conformational analysis. Our inability to find a systematic study comparing the results obtained by various computational methods for carbohydrate modeling led us to compare two different conformational analysis techniques, four different force fields, and three different solvent models. The computational models were compared based on their ability to reproduce experimental coupling constants for sialic acid, sialyl-1,4-lactone, and sialyl-1,7-lactone derivatives. This study has shown that the MM3 forcefield using the implicit solvent model for water implemented in Macromodel best reproduces the experimental coupling constants. The low-energy conformations generated by this combination of computational methods are pre-organized toward conformations which fit well into the active site of neuraminidase.