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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 469 records · Page 26Linked to original sources

Cardiogenic oscillations of He and SF6 in expired gas in dogs.

Quantitative analysis of cardiogenic oscillations of He and SF6 during airway and venous loading demonstrated that both VA/Q and VA/VA inequalities were involved in the lung gas inhomogeneity producing cardiac oscillations in the expirogram. Both inequalities were coupled in such a manner that low VA/Q units had high VA/VA. The oscillations were modified in conducting airways where SF6 oscillations were attenuated more than He oscillations, probably by laminar Taylor dispersion.

Animals↗

Significance of cardiogenic mixing in dog lungs.

Single-breath washout of two inert gases (He and SF6) in anesthetized mechanically ventilated dogs in normal conditions with the heart beating and during reversible heart arrest revealed no effects attributable to the action of the beating heart. It is concluded that in the conditions of the experiments convective mixing by the cardiac action played an insignificant role in promoting intrapulmonary mixing and transport.

Animals↗

Gas mixing in dog lungs during high frequency ventilation studied by partial washout-single exhalation technique.

Gas mixing was studied in 10 anesthetized paralyzed dogs during high-frequency low tidal ventilation (HFV). After simultaneous washin of ethane (1%) and washout of resident argon (0.9%) the gas inflow was switched to atmospheric air for varied time intervals leading to varied levels of C2H6 washout and Ar washin. After the stop of HFV at predetermined test gas washout/washin levels, a constant-flow exhalation by a servo ventilator was performed and expirograms of C2H6 and Ar were recorded. Measurements were performed at varied ventilation frequencies (10-40 Hz), stroke volumes (20-40 ml), lung volumes (730-830 ml), expiratory flow rates (0.1-0.01 L/sec), breath-holding prior to exhalation (0-12 sec) and test gas washout levels achieved by varying the washout time (1 to 65 sec) before onset of exhalation. The expirograms showed a close to linearly rising alveolar plateau. They were analyzed for series dead space and alveolar slope which was normalized to the initial-to-final partial pressure difference. The normalized slopes of C2H6 washout and Ar washin were averaged, whereby the effect of shrinking lung volume due to continuing CO2/O2 exchange at low R was assumed to be suppressed. The slope was little affected by changes of stroke volume, decreased slightly with increasing frequency, and decreased considerably with breath-holding or increasing lung volume. As washout progressed, the alveolar slope first increased, attained a maximum at about half-washout and thereafter decreased. The finite values of the alveolar slope indicated that intrapulmonary gas mixing during HFV was incomplete. The slopes were larger than expected from diffusion calculations on symmetrically branching lung models. The behavior of the slope at varied washout levels suggested involvement of parallel ventilation/volume inhomogeneity coupled with sequential emptying.

Animals↗

Multiple breath washout of He and SF6 in panting dogs.

Pulmonary gas transport mechanisms in panting were studied by multiple breath washout of two poorly soluble inert gases of similar solubility but different diffusivity (He and SF6). The experiments were performed in 6 chronically tracheotomized conscious dogs (mean body weight 31.0 kg) which, upon exposure to elevated room temperature, were enforced to thermal panting (mean breathing frequency 288/min). After equilibration of lung gas with 1% He and 1% SF6 followed by changeover to test gas-free air, end-tidal gas concentrations during multiple breath washout were recorded by mass spectrometry. The washout time course was analyzed into 3 exponential components. The initial fast component was considered to be in part determined by the transient response of the measuring system, whereas the intermediate and the slow component could be attributed to lung washout. The mean He/SF6 ratio of medium and slow rate constants was 1.06 and 1.13, respectively (both values differing from 1.0 at P less than 0.001). It is concluded that gas transport in dog lungs during panting was mainly determined by convection, diffusion-dependent processes being discernible but playing a minor role.

Animals↗

Sloping alveolar plateaus of CO2, O2, and intravenously infused C2H2 and CHClF2 in the dog.

To investigate the role of the various mechanisms assumed to contribute to the slope of the alveolar plateau, two test gases exhibiting identical solubility but two-fold differing diffusivity, acetylene (C2H2) and chlorodifluoromethane (Freon 22, CHClF2), dissolved in saline were intravenously infused in 10 anesthetized, paralyzed, artificially ventilated dogs (mean body mass, 18 kg). The partial pressures of C2H2, CHClF2, CO2 and O2 during a constant-flow single-breath washout maneuver were recorded by mass spectrometry and analyzed in terms of slope of the alveolar plateau (phase III) and series (Fowler) dead space. The slope of the alveolar plateau (S) was determined as the relative alveolar slope normalized to mixed-expired partial pressure and referred to expired volume (VE), S(V) = delta PE/(PE - PI)/delta VE or expiration time (tE), S(t) = delta PE/(PE - PI)/delta tE (subscripts I, E, and E refer to inspired, instantaneous expired and mixed-expired gas, respectively). The effects of expiratory flow rate (VE), and time of breath-hold (BH) were studied with reference to control conditions (VI = 0.5 L.sec-1, VE = 0.1 L.sec-1, VI = 50% and VE = 75% of volume at FRC, BH = 0 sec). In control conditions, the following significantly different S(V) values (units: L-1), grouped in ascending order, were obtained (means +/- SD): CO2, 0.83 +/- 0.26; C2H2, 0.93 +/- 0.18; CHClF2, 1.00 +/- 0.20; O2, 1.07 +/- 0.29. The mean C2H2/CHClF2 ratio for S(V), 0.94 (SD +/- 0.03), was statistically different from unity. In line with model calculations, the experimental findings suggest that three mechanisms contribute to the sloping alveolar plateaus: 1, continuing gas exchange during expiration; 2, ventilation-perfusion inequality combined with sequential emptying; 3, intrapulmonary diffusion limitation.

Acetylene↗

Base changes at position 792 of Escherichia coli 16S rRNA affect assembly of 70S ribosomes.

To investigate the function of base 792 of 16S rRNA in 30S ribosomes of Escherichia coli, the wild-type (adenine) residue was changed to guanine, cytosine, or uracil by oligonucleotide-directed mutagenesis. Each base change conferred a unique phenotype on the cells. Cells containing plasmid pKK3535 with G792 or T792 showed no difference in generation time in LB broth containing ampicillin, whereas cells with C792 exhibited a 20% increase in generation time in this medium. To study the effect on cell growth of a homogeneous population of mutant ribosomes, the mutations were cloned into the 16S rRNA gene on pKK3535 carrying a spectinomycin-resistance marker (thymine at position 1192), and the cells were grown with spectinomycin. Cells containing G792 or C792 showed 16% and 56% increases in generation time, respectively, and a concomitant decrease in 35S assimilation into proteins. Cells with T792 did not grow in spectinomycin-containing medium. Maxicell analyses indicated decreasing ability to form 70S ribosomes from 30S subunits containing guanine, cytosine, or uracil at position 792 in 16S rRNA. It appeared that C792-containing 30S ribosomes had lost the ability to bind initiation factor 3.

Base Sequence↗

A trans-activator function is generated by integration of hepatitis B virus preS/S sequences in human hepatocellular carcinoma DNA.

The X gene of wild-type hepatitis B virus or integrated DNA has recently been shown to stimulate transcription of a variety of enhancers and promoters. To further delineate the viral sequences responsible for trans-activation in hepatomas, we cloned the single hepatitis B virus insert from human hepatocellular carcinoma DNA M1. The plasmid pM1 contains 2004 base pairs of hepatitis B virus DNA subtype adr, including truncated preS/S sequences and the enhancer element. The X promoter and 422 nucleotides of the X coding region are present. The entire preC/C gene is deleted. In transient cotransfection assays using Chang liver cells (CCL 13), pM1 DNA exerts a 6- to 10-fold trans-activating effect on the expression of the pSV2CAT reporter plasmid. The trans-activation occurs by stimulation of transcription and is dependent on the simian virus 40 enhancer in the reporter plasmid. Deletion analysis of pM1 subclones reveals that the trans-activator is encoded by preS/S and not by X sequences. A frameshift mutation within the preS2 open reading frame shows that this portion is indispensable for the trans-activating function. Initiation of transcription has been mapped to the S1 promoter. A comparable trans-activating effect is also observed with cloned wild-type hepatitis B virus sequences similarly truncated. These results show that a transcriptional trans-activator function not present in the intact gene is generated by 3' truncation of integrated hepatitis B virus DNA preS/S sequences.

Carcinoma, Hepatocellular↗

A multi-level intervention approach for care of HIV-positive haemophiliac and thalassaemic patients and their families.

The experience gained from the application of an on-going multilevel intervention programme through an interdisciplinary team approach to the management of 30 HIV-positive children, adolescents and young people aged from 7 to 21 years (20 haemophiliac and 10 thalassaemic patients) and their families is described. The objective of the intervention was to assess the family's needs, to help parents and other family members to contain the anxiety of seropositive children and to improve their interraction with the family as well as with others in their social environment. The intervention was also designed to help family members to cope with their grief. Work with the medical and nursing staff, on the other hand, was intended to increase their understanding of the emotions caused in them by occupational stress, such as fear, anxiety, prejudice and feelings of guilt related to the iatrogenous nature of the infection. The need for follow-up studies is stressed to allow assessment of the effectiveness of the intervention and to search for protective factors, successful coping skills, strategies and adaptational resources.

Adaptation, Psychological↗

Regional and cellular codistribution of interleukin 1 beta and nerve growth factor mRNA in the adult rat brain: possible relationship to the regulation of nerve growth factor synthesis.

We have found a regional distribution of IL 1 beta mRNA and IL 1 activity in the normal adult rat brain, which reveals at least partially a colocalization with nerve growth factor (NGF). The predominantly neuronal signal patterns were found over the granule cells of the dentate gyrus, the pyramidal cells of the hippocampus, the granule cells of the cerebellum, the granule and periglomerular cells of the olfactory bulb, and over dispersed cells of the ventromedial hypothalamus and of the frontal cortex. In these areas also the highest levels of IL 1 activity were observed. In the striatum and septum much lower levels of IL 1 beta mRNA and IL 1 activity (shown for the striatum), most likely synthesized by glial cells, could be determined. IL 1 beta-expressing cells were mainly found in brain regions that also synthesize NGF mRNA as shown by in situ hybridization. NGF mRNA could be demonstrated over pyramidal cells of the hippocampus, granule cells of the dentate gyrus, periglomerular cells of the olfactory bulb and over prefrontal cortex neurons. These data indicate that IL 1 beta, among other factors, might also play a regulatory role in the synthesis of NGF in the CNS, as has been demonstrated in the peripheral nervous system (Lindholm, D., R. Heumann, M. Meyer, and H. Thoenen. 1987. Nature (Lond.). 330:658-659).

Animals↗

The use of duplex Doppler ultrasonography to evaluate renal allograft dysfunction.

This study evaluated the utility of duplex Doppler sonograms (DS) and the resistive index (RI) in the identification and differential diagnosis of various causes of renal allograft dysfunction. The efficacy of DS and RI was studied either during acute episodes of allograft dysfunction or during periodic posttransplantation longitudinal analyses. The unique features of each renal allograft results in poor correlative value for single isolated measurements of RI. We observed that the highest RIs were in ATN and that an RI of 0.9 was not specific for acute vascular rejection. Also, an RI of 0.9 was rare in acute cellular rejection. RI could not distinguish acute rejection, chronic rejection, CsA toxicity, or obstruction, although the mean RI was significantly different from normal in these groups. Serial studies of RI did document a change at the time of a clinical event compared to baseline. It is concluded that RI is not specific to any one clinical entity.

Cyclosporins↗

Cryopreservation of human embryos as a useful tool for infertile couples.

In order to improve the pregnancy rate per oocyte retrieval while reducing the chance of multiple-gestations, a technique of cryopreservation of human embryos was used for our initial study consisting of 100 infertile patients undergoing in vitro fertilization (IVF) procedure. These patients combined a "fresh" embryo transfer with cryopreservation. The embryos were cryopreserved with 1,2-propanediol. Twenty-nine (29%) patients achieved ongoing pregnancies from the fresh embryo transfer. Thirty patients received a transfer of thawed embryos in a natural cycle. Nine of these patients achieved ongoing pregnancies. Combining these 2 transfers results in a 38% ongoing pregnancy rate. Forty-one patients have yet to receive their frozen embryos. The current success rate in this study indicates that over 50% of the patients in this group can expect to become pregnant by the time all the cryopreserved embryos have been transferred.

Cryopreservation↗

Purification of NADPH-dependent electron-transferring flavoproteins and N-terminal protein sequence data of dihydrolipoamide dehydrogenases from anaerobic, glycine-utilizing bacteria.

Three electron-transferring flavoproteins were purified to homogeneity from anaerobic, amino acid-utilizing bacteria (bacterium W6, Clostridium sporogenes, and Clostridium sticklandii), characterized, and compared with the dihydrolipoamide dehydrogenase of Eubacterium acidaminophilum. All the proteins were found to be dimers consisting of two identical subunits with a subunit Mr of about 35,000 and to contain about 1 mol of flavin adenine dinucleotide per subunit. Spectra of the oxidized proteins exhibited characteristic absorption of flavoproteins, and the reduced proteins showed an A580 indicating a neutral semiquinone. Many artificial electron acceptors, including methyl viologen, could be used with NADPH as the electron donor but not with NADH. Unlike the enzyme of E. acidaminophilum, which exhibited by itself a dihydrolipoamide dehydrogenase activity (W. Freudenberg, D. Dietrichs, H. Lebertz, and J. R. Andreesen, J. Bacteriol. 171:1346-1354, 1989), the electron-transferring flavoprotein purified from bacterium W6 reacted with lipoamide only under certain assay conditions, whereas the proteins of C. sporogenes and C. sticklandii exhibited no dihydrolipoamide dehydrogenase activity. The three homogeneous electron-transferring flavoproteins were very similar in their structural and biochemical properties to the dihydrolipoamide dehydrogenase of E. acidaminophilum and exhibited cross-reaction with antibodies raised against the latter enzyme. N-terminal sequence analysis demonstrated a high degree of homology between the dihydrolipoamide dehydrogenase of E. acidaminophilum and the electron-transferring flavoprotein of C. sporogenes to the thioredoxin reductase of Escherichia coli. Unlike these proteins, the dihydrolipoamide dehydrogenases purified from the anaerobic, glycine-utilizing bacteria Peptostreptococcus glycinophilus, Clostridium cylindrosporum, and C. sporogenes exhibited a high homology to dihydrolipoamide dehydrogenases known from other organisms.

Amino Acid Sequence↗

Serum enhancement of human immunodeficiency virus (HIV) infection correlates with disease in HIV-infected individuals.

The sera from 16 individuals infected with the human immunodeficiency virus (HIV) at different clinical stages were evaluated for antibody-dependent neutralization and/or enhancement of infectivity by HIV. The HIV isolate from each individual (homotypic) and established laboratory strains showing broad cellular host range and cytopathicity were used. All sera could neutralize one of the laboratory-passaged isolates, whereas only two could neutralize the corresponding homotypic strain. Seven homotypic isolates were enhanced by serum from the respective individual. This activity was primarily observed in patients with acquired immune deficiency syndrome. Moreover, the tropism for macrophages of four of these seven viral isolates was found to be enhanced by the homotypic sera. Finally, sequential pairs of HIV and sera obtained from five HIV-infected individuals with different clinical progression were studied over time. The enhancing activity of three of the five sera appeared to increase over time, indicating changes in both the host virus population and the type of antibodies produced. These results suggest that enhancing antibodies contribute to the spread and pathogenesis of HIV in vivo. They emphasize the necessity of studying further the association of enhancing antibodies and disease progression in infected individuals.

AIDS-Related Complex↗

Interaction of the Bacillus sphaericus mosquito larvicidal proteins.

Genes for 51.4- and 41.9-kDa insecticidal proteins of Bacillus sphaericus were separately cloned and expressed in Escherichia coli. Both proteins were required for toxicity. Approximately equal numbers of cells containing the 51.4- and 41.9-kDa proteins produced the greatest toxicity; excess 41.9-kDa protein did not affect toxicity, whereas excess 51.4-kDa protein reduced activity. Larvae were killed when 41.9-kDa protein was fed up to 24 h after the 51.4-kDa protein, but not when the order of feeding was reversed. Radiolabelled toxins bound in approximately equal amounts to the gastric caecum and posterior midgut of Culex quinquefasciatus larvae. Radiolabelled 51.4-kDa protein was rapidly degraded by ca. 12-13 kDa in the larval gut, while 41.9-kDa protein was degraded by 1-2 kDa. Nonreduced toxin extracted from B. sphaericus produced a band on SDS-PAGE of ca. 68-74 kDa that contained both 51.4- and 41.9-kDa proteins based on sequence analysis, and a band of ca. 51 kDa that contained primarily 41.9-kDa protein. Escherichia coli containing 51.4-kDa protein enhanced toxicity of the latter eluted SDS-PAGE band. These proteins may associate very strongly, and trace amounts of 51.4-kDa protein in preparations of 41.9-kDa protein from B. sphaericus may be responsible for the previously reported toxicity of the latter.

Amino Acid Sequence↗