Precision measurement of the Ds*+-Ds+ mass difference.
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Biomedical subjects
Publications and source records attributed to G Wei.
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Many lines of evidence indicate that in Drosophila the mechanism for establishing the sex of the female germline is different from that acting in somatic cells. In the soma Sxl has an embryonic determinative role and is required throughout the life of female flies; in germ cells its expression begins only in the larval ovary. Both the mechanism for activating Sxl and the genes controlled by Sxl are different in the germline. A number of genes have been identified that are essential either for survival (e.g. ovo, otu) or differentiation (snf, Sxl, fl(2)d, bgcn) of female germ cells. ovo is required during embryogenesis for survival of pole cells. Genetic interactions with dominant alleles of ovo and/or Sxl indicate that otu, Sxl, snf and fl(2)d act in the same pathway as does ovo. bgcn differs in that neither ovo nor SxlD mutations affect the bgcn phenotype even though XX bgcn germ cells enter the male pathway. bgcn causes sterility in both sexes. Although the germline defect is cell autonomous in mosaic gonads, bgcn is also required in the somatic tissue for maintaining oogenesis of wild-type germ cells. Several dominant suppressors of bgcn have been identified and some have properties similar to Suppressors of variegation, suggesting that chromatin structure is critical for proper germ cell sex determination.
Vigabatrin (VGB), an irreversible inhibitor of GABA, is being developed as an add-on therapy for uncontrolled complex partial seizure. A single-dose study was conducted in three groups of subjects with normal, mild-to-moderate, and moderate-to-severe renal impairment to examine the effect of renal function on the pharmacokinetics of VGB. Serial blood samples were collected up to 60 h following a single 750 mg oral dose of VGB for the quantitation of drug concentrations. The plasma VGB concentration-time data were analyzed by mixed-effects modeling to estimate population pharmacokinetic parameters and to identify any significant demographic covariates. The parameters of VGB were also calculated by standard two-stage techniques and then compared to the results obtained using the mixed-effects analysis. Population VGB plasma concentration-time profiles were best described by a two-compartment model with zero-order absorption. Creatinine clearance was observed to significantly affect the oral clearance of VGB (p < 0.05), i.e. a linear increasing relationship existed between the two variables. Other demographic factors had no influence on VGB pharmacokinetics. There were agreements in the oral clearance, apparent volume of distribution during elimination, and half-life estimates calculated by both methods. In addition, the conventional technique identified a linear relationship between oral and creatinine clearances. In summary, mixed-effects modeling of serial vigabatrin data validated results determined by the standard two-stage technique.
Mutations at a few genetic loci in Drosophila cause ovarian tumors with hundreds of poorly differentiated germ cells. We examined several of these mutants to test the hypothesis that such ovarian tumors contain sex-transformed cells. By testing for expression of male germline traits, we determined that partial germline sex transformation occurs in otu, snf, Sxlfs, and bam ovarian tumors. Thus these genes are likely to be required for proper establishment of germline sexual identity.
Transplantations of both Drosophila pole cells and mouse primordial germ cells suggest that the pregonadal germline of these two organisms is not pluripotent. In mouse PGCs, however, the potential for activating pluripotency is clearly present, as seen in the relative case of deriving EG cells from migratory-stage PGCs. EG cells are derived from altering the in vitro growth conditions of PGCs by the addition of one factor. Conceivably, straying of PGCs in vivo could also lead to novel fates if they migrated into a suitable environment. Aberrant PGC migration underlies models for the origin of several tumor types. How are migratory-stage PGCs prevented from adopting alternative fates in wild-type development? One solution is to link accurate migration into the gonads with germ cell survival. One mechanism of accomplishing this is through the action of pleiotrophic factors such as Steel. Steel is both a proliferation and migration factor; sterility in Steel mutants is due to poor germ cell survival and improper migration. Networking of migratory PGCs is another mechanism to reduce the chances of individual germ cells straying from the migration path. Postmigratory germ cells apparently undergo another restriction on potency--novel imprinting. Assuming that EG methylation profiles accurately reflect modifications made in their founder PGCs, then "erased" pluripotent EG lines suggest that PGCs can be diverted from the germline lineage. Direct assays on PGCs show that the unmethylated phenotype at Igf2r region 2 is characteristic of late germ cells. The maintenance of germline-like methylation with a switch in PGC fate is somewhat analogous to the situation in lag mutants from Volvox, which retain large gonidial-sized cells that can nevertheless initiate somatic differentiation. Just as it is not possible to readjust cell size with a subsequent change in gonidial differentiation, it may be difficult, without gametogenesis, to reimpose methylation modifications once they have been erased. In addition, the methylation status of some sites/loci may be inconsequential to developmental gene activity in germ cells or EG cells. Recent studies indicate that the methylation imprint at Igf2r is not interpreted at functional level until embryogenesis (51). In summary, we have reviewed some distinctive properties of the development of germ cells, from their early segregation, mitotic and meiotic profile, sex determination, to their migration and sequestration into gonads. Some constraints on development of the germline likely serve to maintain its integrity until maturation, when the gametic genomes must be capable of initiating embryonic development. To accomplish this ultimate goal, germ cells in some organisms may retain a bias towards pluripotency throughout development.(ABSTRACT TRUNCATED AT 400 WORDS)
Gamma radiolysis of metallothionein (MT) in phosphate-buffered solutions at pH 8.0 leads to the formation of intra- and intermolecular disulfide bridges as well as the release of chelated metal ions. When MT solutions deaerated with N2 or saturated with N2O were irradiated, G values for RS- loss as determined by Ellman's reagent were 4.2 and 7.0, respectively, whereas those for dimerization were only 0.32 and 0.67. A short chain reaction existed in the decrease in RS- when radiolysis was performed in O2-saturated solutions. The rate constants for reactions of MTs with OH radical and H2O2 were measured to be about 10(12) and 100 M-1 s-1, respectively. A mechanism for the radiolysis of MT-1 is proposed.
Characteristics of human vertical optokinetic nystagmus (VOKN) and afternystagmus (VOKAN) were examined by electro-oculography in 18 normal human subjects by means of the analysis of slow phase velocity (SPV) and area under the regression curve of the VOKAN decay. Under normal gravity, subjects were tested in upright and left ear down (90 degrees roll) positions, respectively, using a hemisphere onto which stripes were projected at a velocity of 40 degrees/s in left, right, up and down directions. Analysis of the VOKN and VOKAN revealed a significant asymmetry of vertical eye movements in the subjects' sagittal plane, ie, stronger upward SPV than downward in both VOKN and VOKAN decay. This asymmetry became even more prominent when the head was in the 90 degrees roll position. It is postulated that the asymmetry of VOKN and VOKAN in humans, as in animals, is due to the asymmetrical storage capability of the vertical velocity storage mechanism which mainly contributes to upward eye movements. In addition, it is postulated that the vertical storage mechanism is modified by the action of gravity on the otolith organs. However, only two out of our 18 subjects demonstrated cross-coupling, as reported in animals, from the horizontal to the vertical mode of storage when the head was tilted away from the spatial vertical.
Cell-mediated, but not antibody-mediated, immune responses protect humans against certain pathogens that produce chronic diseases such as leishmaniasis. Effective vaccination against such pathogens must therefore produce an immunological "imprint" so that stable, cell-mediated immunity is induced in all individuals after natural infection. BALB/c mice "innately susceptible" to Leishmania major produce antibodies after substantial infection. In the present study, "susceptible" mice injected with a small number of parasites mounted a cell-mediated response and acquired resistance to a larger, normally pathogenic, challenge. This vaccination strategy may be applicable in diseases in which protection is dependent on cell-mediated immunity.
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In routine clinical electronystagmographic (ENG) tests (postrotatory, optokinetic, caloric and tracking tests), eye movement signals were analyzed and a multiple discriminant analysis was carried out with the aid of a microcomputer. Six parameters were selected and, based on these, two functions for discriminating between peripheral and central disorders were established. Discrimination between 35 patients with peripheral lesions and 15 patients with central lesions was made with a correct classification rate of 97.1 and 86.7%, respectively. These rates are significantly higher than that of any single ENG test analysis. Our results indicate that the clinical application of ENG can be improved by searching for more sensitive ENG parameters and adopting the comprehensive analysis approach.
The 4-year experience in the clinical usage of titanium nails in making internal fistula for hemodialysis in 428 cases (17,829 dialyses) is reported. The results were satisfactory and no obvious complications were found. Being simple in practice and having a high success rate and less complications, this method has been applied at 86 hospitals in China.
Stimulus velocity dependence of human VOKN and VOKAN was investigated using 20 degrees, 40 degrees, 60 degrees, and 80 degrees/s optokinetic stimulation. In our experimental conditions, 40 degrees/s was found to be the most appropriate stimulus velocity for inducing reliable VOKN and VOKAN based on the analysis of SPV, gain, and the area under the VOKAN decay curve. There was a clear trend toward up/down asymmetry of VOKN gain, with higher upward OKN SPV than downward at 40 degrees/s. VOKAN with both short and long time constant components was induced in 5 of 11 subjects, but only when the stimulus was upgoing. Stimulation at 20 degrees/s in either direction produced a decay with only a short time constant. VOKN-SPV and the area under VOKAN decay curve at 40 degrees/s showed no significant difference from the corresponding values at 60 degrees/s or 80 degrees/s, indicating that following and the velocity storage mechanism had saturated at 40 degrees/s. However, the gain at 60 degrees/s and 80 degrees/s became low and eye movement regularity was poor. Stimulation at 20 degrees/s may activate mainly the vertical pursuit mechanism, as it did not produce up/down asymmetry. It is proposed that, as in the horizontal case, two kinds of mechanisms are involved in vertical stripe-following eye movements, which represent smooth pursuit and optokinetic systems respectively.
In hybrid dysgenesis, sterility can occur in both males and females. At 27.5 degrees, however, we found that P element-induced germline death was restricted to females. This sex-specific gonadal dysgenesis (GD) is complete by the first larval instar stage. As such, GD at 27.5 degrees reveals the sexually dimorphic character of the embryonic germline. The only other known dimorphic trait of the embryonic germline is the requirement for ovo. ovo is required for germline development in females only and has been implicated in germline sex determination. Dominant mutations of ovo partially suppressed female GD. Although embryonic germ cells are undifferentiated and morphologically indistinguishable between males and females, the functional dimorphism seen in ovo requirement and GD at 27.5 degrees indicates that sexual identity in Drosophila germ cells is established in embryogenesis.
We prepared a composite of D,L-lactic acid oligomer and dideoxykanamycin B for use as a biodegradable antibiotic delivery system with sustained effect. The composite was implanted in the distal portion of the rabbit femur, and the effective concentration of the antibiotic was measured in the cortex, the cancellous bone, and the bone marrow. In all bone tissues around the implant, the concentration of antibiotic exceeded the minimum inhibitory concentration for the common causative organisms of osteomyelitis for six weeks. Most of the implant material had been absorbed and the bone marrow had been repaired to a nearly normal state within nine weeks of implantation. The implant caused no systemic side effects, and it is likely to prove clinically useful as a drug delivery system for treating chronic osteomyelitis.
To test the hypothesis that auditory inputs can interact with the optokinetically or vestibularly-charged human VSM, we examined the effects of sound on rotational nystagmus and HOKAN. Subjects were rotated at 60 degrees/s, in either clockwise (CW) or counterclockwise (CCV) direction, for a total of 3 min. After 1 min of constant rotation, the optokinetic surround (7 ft dia., 2 degrees stripes at 18 degrees intervals) was illuminated for 60 s and the ensuing HOKAN was recorded for 60 s (standard DCEOG). The chair was stopped 60 s later and the post-rotatory nystagmus (PRN) was recorded. The acoustic stimulus (4/s, 10 ms pulses) was presented to the subject by a loudspeaker in 4 randomized test conditions: (1) fixed to the surround-on during OKN, off during OKAN (2) fixed to the surround-off during OKN, on during OKAN (3) rotating with the subject-on during OKN, off during OKAN (4) rotating with the subject-off during OKN, on during OKAN. In all conditions, the sound was on during per- and post-rotatory nystagmus. Each test was performed on a different day and consisted of 4 randomized control and test trials (CW and CCW). Under none of the above conditions was the rotatory or optokinetic decay affected by the presence of stationary or rotating sound. This absence of alteration of PRN by sound cues contradicts that reported by Kollar et al. (1988). Our evidence that neither HOKAN nor post rotatory nystagmus decay is affected by sound cues supports the conclusion that, under our conditions, multisensory interaction does not occur in the human VSM.
Inoculating Schizonepeta tenuifolia with VA mycorrhizal fungi can significantly improve the plant growth and uptake of P and S, and influence the absorption of K, Na, Fe, Mo, Mn, Zn, Co, Ba, Ni and Pb. It is interesting to note that VA mycorrhiza can also increase the synthesis of volatile oil in the shoots of S. tenuifolia. The efficiency of VA mycorrhiza varies with the fungal species.