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Biomedical subjects

K Meyer

Publications and source records attributed to K Meyer.

At least 145 records · Page 8Linked to original sources
PubMed1996

Effects of short-term exercise training and activity restriction on functional capacity in patients with severe chronic congestive heart failure.

Previous exercise training studies in patients with chronic congestive heart failure (CHF) were performed for periods lasting > 2 months, and effects of activity restriction on exercise induced-benefits were not systematically assessed. With one exception study, patients were not reported to be transplant candidates. In this random-order crossover study, effects of 3 weeks of exercise training and 3 weeks of activity restriction on functional capacity in 18 hospitalized patients with severe CHF [(mean +/- SEM) age 52 +/- 2 years; ejection fraction 21 +/- 1%; half of them on a transplant waiting list] were assessed. The training program consisted of interval exercise with bicycle ergometer (15 minutes) 5 times weekly, interval treadmill walking (10 minutes), and exercises (20 minutes), each 3 times weekly. With training, the onset of ventilatory threshold was delayed (p < 0.001), with increased work rate by 57% (p < 0.001) and oxygen uptake by 23.7% (p < 0.001). On average, there was a 14.6% decrease in slope of ventilation/carbon dioxide production before the onset of ventilatory threshold (p < 0.05), and ventilatory equivalent of carbon dioxide production by 10.3% (p < 0.01). At the highest comparable work rate (56 +/- 5 W) the following variables were decreased: heart rate (7.3%; p < 0.05), lactate (26.6%; p < 0.001), and ratings of perceived leg fatigue and dyspnea (14.5% and 16.5%; p < 0.001 each). At peak exercise, oxygen uptake was increased by 19.7% (p < 0.01) and oxygen pulse by 14.2% (p < 0.01). There was a correlation of baseline peak oxygen uptake and increase of peak oxygen uptake due to training (r = -0.75; p < 0.004). Independently of the random order, data after activity restriction did not differ significantly from data measured at baseline. Patients with stable, severe CHF can achieve significant improvements in aerobic and ventilatory capacity and symptomology by short-term exercise training using interval exercise methods. Impairments due to activity restriction suggest the need for long-term exercise training.

Chronic Disease↗
PubMed1996

Mutagenicity and mutational spectra of 1,3-butadiene in the bone marrow of B6C3F1 lacI transgenic mice.

We are using B6C3F1 lacI transgenic mice to investigate the in vivo mutagenicity and mutational spectra of 1,3-butadiene (BD). Male B6C3F1 lacI transgenic mice were exposed by inhalation to 0, 62.5, 625, or 1250 ppm BD for 4 weeks (6 h/day, 5 days/week). Tissues were collected 2 weeks after the final exposure for mutant frequency analysis. The lacI- mutant frequency in bone marrow from BD-exposed mice was increased 2- to 3.5-fold over air control mice. Analysis of the mutational spectrum of lacI mutants isolated from the bone marrow of lacI mice exposed to 625 ppm BD indicated a shift in the mutational spectrum at A:T base pairs relative to air controls: 2/41 point mutations occurred at A:T base pairs in air controls versus 6/24 in BD-exposed animals; 10/40 mutations occurred at A:T base pairs in lacI mice exposed to 1250 ppm BD. A-->T transversions were found only in BD-exposed animals. Although there was a reduction in the proportion of GC-->AT transitions at 5'-CpG-3' sites recovered from the bone marrow of BD-exposed mice (25%) relative to air controls (50%), there was no difference in the contribution of GC-->AT transitions at 5'-CpG-3' sites to the mutation frequency in BD-exposed mice compared to air controls. Since the bioactivation of BD by B6C3F1 mice produces at least two mutagenic metabolites epoxybutene (EB) and diepoxybutane (DEB), studies on the in vivo mutational spectra begin to provide the framework for the ultimate identification of the BD metabolite(s) responsible for the specific mutations observed.

Animals↗
PubMed1996

Ferulate-5-hydroxylase from Arabidopsis thaliana defines a new family of cytochrome P450-dependent monooxygenases.

The fah1 mutant of Arabidopsis is defective in the accumulation of sinapic acid-derived metabolites, including the guaiacyl-syringyl lignin typical of angiosperms. Earlier results indicated that the FAH1 locus encodes ferulate-5-hydroxylase (F5H), a cytochrome P450-dependent monooxygenase (P450) of the general phenylpropanoid pathway. We have cloned the gene encoding this P450 by T-DNA tagging and have confirmed the identity of the cloned gene by complementation of the mutant phenotype. F5H shows 34% amino acid sequence identity with the avocado ripening-induced P450 CYP71A1 and 32% identity with the flavonoid-3',5'-hydroxylases of Petunia hybrida. In contrast, it shares much less homology with cinnamate-4-hydroxylase, a P450 that catalyzes the hydroxylation of cinnamic acid three steps earlier in the general phenylpropanoid pathway. Since the highest degree of identity between F5H and previously sequenced P450s is only 34%, F5H identifies a new P450 subfamily that has been designated CYP84.

Alleles↗
PubMed1996

Rhinovirus enters but does not replicate inside monocytes and airway macrophages.

Potential interactions between rhinovirus (RV) and both the airway macrophage and its precursor cell, the blood monocyte, were investigated in terms of direct binding, intracellular replication, cell survival, and cytokine production. When HeLa cell suspensions are inoculated with RV as a positive control, virus titer increases by 100-fold in the first 24 h, confirming intracellular replication. In contrast, RV titer in monocyte and macrophage suspensions steadily decreased. Despite a lack of productive RV replication, cell-associated RV RNA was detectable using a biotin-labeled cDNA probe as early as 6 h after inoculation. Direct binding of RV16 to macrophages was confirmed using radiolabeled virus, although preincubation with anti-ICAM-1 mAb did not block this interaction. Synthesis of RV RNA, as indicated by [3H]uridine incorporation in actinomycin D-treated cells, was detected in HeLa cells but not macrophages, suggesting that the viral RNA detected inside macrophages was from input virus and was not newly synthesized. RV inoculation did not adversely affect monocyte or macrophage viability. Finally, RV caused macrophage activation, as indicated by the induction of TNF-alpha secretion. These in vitro findings suggest that macrophages interact with major group RV in vivo, and raise the possibility that there is a second cellular receptor for these viruses. Furthermore, macrophages do not serve as permissive host cells during in vivo RV infection, but instead may be active participants in anti-RV immunity and RV-induced airway inflammation.

Antibodies, Monoclonal↗
PubMed1996

Cardiopulmonary determinants of functional capacity in patients with chronic heart failure compared with normals.

BACKGROUND: Patients with chronic heart failure (CHF) are characterized by abnormal gas exchange and ventilatory responses to exercise. HYPOTHESIS: This study compares variables obtained from cardiopulmonary exercise testing in 35 patients with CHF with 35 age- and weight-matched healthy subjects. A second goal was to obtain cardiopulmonary variables measured at ventilatory threshold to distinguish patient changes from those of healthy subjects. METHODS: Exercise testing was carried out using bicycle ergometry with ramplike protocol (work rate increments 12.5 W/min). Gas exchange and ventilation were measured breath by breath. RESULTS: Compared with healthy subjects, the VO2 in patients was lower at identical work rates (p < 0.004) and at ventilatory threshold (p < 0.0001), and the slope of the VO2 curve during incremental exercise was flatter (p < 0.05). With the exception of heart rate, the variables for VO2, VCO2, ventilation, O2 pulse, ventilatory equivalents for O2 and CO2, and VD/VT (physiologic deadspace to tidal volume ratio), as well as lactate differed significantly at identical work rates. With the exception of VD/VT, all cardiopulmonary variables showed significant differences in their slopes during exercise. By means of a discriminant analysis, VCO2 and ventilation proved to be the most distinguishing variables at ventilatory threshold between patients with CHF and healthy subjects. CONCLUSIONS: These results indicate the clinical usefulness of cardiopulmonary exercise testing when assessing functional impairment due to CHF. For treatment evaluation, not only VO2 but also VCO2 and ventilation responses to exercise should be considered.

Adult↗
PubMed1996

Ventilatory and lactate threshold determinations in healthy normals and cardiac patients: methodological problems.

In healthy normal individuals (n = 69), coronary patients with myocardial ischaemia (n = 27) and patients with chronic heart failure (CHF, n = 33), four widely applied methods to determine ventilatory threshold (VT) were analysed: V-slope, ventilatory equivalent for O2 (EqO2), gas exchange ratio (R) and end-tidal partial pressure of oxygen. Lactate threshold [LAT, log lactate vs log oxygen uptake (VO2)] was also determined. Analysis focused on rate of success of threshold determination, comparability of threshold methods, reproducibility and interobserver variability. Cycle ergometry protocols with ramp-like mode and graded steady-state mode used in exercise testing were considered separately. In healthy normal individuals and coronary patients with myocardial ischaemia, at least three VT could be determined during ramp-like mode and two VT during graded steady-state mode, 82% of the time. For CHF patients, the rate of successful determination of VT was lower. Compared to LAT, VO2 at VT was significantly higher using R and EqO2 methods of VT determination in healthy normal subjects (P < 0.01), and significantly higher when using all four methods in coronary patients (P < 0.01 or P < 0.05, respectively). No difference was observed between VO2 at VT and LAT in CHF patients. In healthy normal individuals, day-to-day reproducibility of VT and LAT was high (error of a single determination from duplicate determinations was between 3.9% and 6.2% corresponding to a VO2 of 52.2 and 89.2 ml.min-1). Interobserver variability was low (error between 0.3% and 5% corresponding to a VO2 of 9.8 and 68 ml.min-1). In CHF patients, interobserver variability was moderately greater (error between 4.6% and 8.2%, corresponding to a VO2 of 35.1 and 62.4 ml.min-1). To optimize threshold determination, standardized procedures are suggested.

Adolescent↗
PubMed1996

Congenital muscular dystrophy with laminin alpha 2 chain deficiency: identification of a new intermediate phenotype and correlation of clinical findings to muscle immunohistochemistry.

UNLABELLED: The laminins comprise of a family of heterotrimeric proteins of the extracellular matrix. The crossshaped proteins consist of a heavy alpha-chain and two light chains, called beta and gamma. Each group of chains, classified on their sequence identity and domain organization, include different isoforms. A deficiency of the alpha 2 chain of laminin-2, previously termed merosin or M component, was shown to be responsible for one form of congenital muscular dystrophy (CMD). We investigated muscle biopsies of 20 patients with the clinical diagnosis of CMD and histological evidence of muscular dystrophy for the expression of different laminin chains. Patients with evidence of pachygyria/lissencephaly of the CNS were excluded from this series. The immunohistochemical analysis was correlated to clinical findings and MRI data of the brain. Of 20 patients, 11 (55%) revealed complete or near-complete deficiency of the alpha 2 chain in their skeletal muscle specimens. So far none of these patients became ambulant. Of 20 patients 2 showed partial but clear-cut alpha 2 chain-deficiency. These two patients became ambulant at 18 months and 3 years. All 13 patients with complete or partial alpha 2 chain-deficiency demonstrated cerebral white matter changes on MRI. In contrast, 6/7 CMD patients with normal alpha 2 chain expression became ambulant and none of the 6/7 tested showed evidence of cerebral abnormal T2 sequence signal of the myelin on MRI. CONCLUSION: Our findings emphasize the use of immunohistochemistry for laminin alpha 2 as a diagnostic tool in defining CMD and characterize a milder phenotype with partial alpha 2 chain-deficiency.

Adolescent↗
PubMed1996

Induction of SIV capsid-specific CTL and mucosal sIgA in mice immunized with a recombinant S. typhimurium aroA mutant.

We have developed a new expression system based on the E. coli groEL promoter. The suicide vector constructed (called APC vector) allows simultaneous attenuation of a Salmonella strain by disruption of the coding sequence for aroA and stable integration of a gene into the bacterial chromosome. High-level expression of antigen is achieved after Salmonella is taken up by macrophages, a major antigen processing cell of the host. The chloramphenicol acetyltransferase (CAT) and the simian immunodeficiency virus capsid (p27gag) genes were cloned downstream of the groEL promoter and expressed within S. typhimurium. By measuring CAT activity, we showed that the groEL promoter was up-regulated during infection of the J774 macrophage line. The immune response to SIV capsid was assessed in Balb/c mice given one oral dose of vaccine. A local mucosal secretory IgA response against SIV capsid was detected but no systemic antibody response to the same antigen. A systemic CTL response was detected as early as 28 days to as late as 70 days post-immunization. CTL activity was MHC restricted (H-2d) and was mediated by CD3+, CD8+, CD4- T-lymphocytes. These results indicate that with only one oral dose of recombinant Salmonella using the APC vector, a systemic CTL response and a mucosal secretory response against the SIV capsid antigen are elicited in a mouse model.

Animals↗
PubMed1996

Hepatitis C virus core protein inhibits human immunodeficiency virus type 1 replication.

We previously demonstrated that hepatitis C virus (HCV) core protein is a strong repressor of human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) basal transcription. In this study, we have localized the HCV core protein-response domain to a region between nucleotides -65 and +3 within the HIV-LTR. Thus, neither the upstream negative regulatory elements, or binding sites for various transcription factors (e.g. NF-kappa B, USF-1, IL2/IL-2R) nor the downstream TAR regions were involved in HCV core-mediated repression. HCV core protein mediated repression of the basal transcriptional activity of HIV-1 LTR was abrogated by the Tat protein. Furthermore, HeLa-T4 cells expressing HCV core protein showed inhibition of HIV-1 replication after acute infection with cell-free HIV. A similar observation was also noted in CD4+ and CD4-lymphocytic cell lines cotransfected with an infectious molecular clone of HIV-1 and the HCV core protein expression vector. Thus, a repression of basal transcription prior to the accumulation of threshold levels of Tat protein appears to restrict HIV-1 transcription and modulate viral replication.

Anti-HIV Agents↗
PubMed1996

Cell swelling activates ATP-dependent voltage-gated chloride channels in M-1 mouse cortical collecting duct cells.

In the present study we used whole-cell patch clamp recordings to investigate swelling-activated Cl-currents (ICl-swell) in M-1 mouse cortical collecting duct (CCD) cells. Hypotonic cell swelling reversibly increased the whole-cell Cl- conductance by about 30-fold. The I-V relationship was outwardly-rectifying and ICl-swell displayed a characteristic voltage-dependence with relatively fast inactivation upon large depolarizing and slow activation upon hyperpolarizing voltage steps. Reversal potential measurements revealed a selectivity sequence SCN- > I- > Br- > Cl- > > gluconate. ICl-swell was inhibited by tamoxifen, NPPB (5-nitro-2(3-phenylpropylamino)-benzoate), DIDS (4,4'-diisothiocyanostilbene-2,2'-disulphonic acid), flufenamic acid, niflumic acid, and glibenclamide, in descending order of potency. Extracellular cAMP had no significant effect. ICl-swell was Ca2+ independent, but current activation depended on the presence of a high-energy gamma-phosphate group from intracellular ATP or ATP gamma S. Moreover, it depended on the presence of intracellular Mg2+ and was inhibited by staurosporine, which indicates that a phosphorylation step is involved in channel activation. Increasing the cytosolic Ca2+ concentration by using ionomycin stimulated Cl- currents with a voltage dependence different from that of ICl-swell. Analysis of whole-cell current records during early onset of ICl-swell and during final recovery revealed discontinuous step-like changes of the whole-cell current level which were not observed under nonswelling conditions. A single-channel I-V curve constructed using the smallest resolvable current transitions detected at various holding potentials and revealed a slope conductance of 55, 15, and 8 pS at +120, 0, and -120 mV, respectively. The larger current steps observed in these recordings had about 2, 3, or 4 times the size of the putative single-channel current amplitude, suggesting a coordinated gating of several individual channels or channel subunits. In conclusion we have functionally characterized ICl-swell in M-1 CCD cells and have identified the underlying single channels in whole-cell current recordings.

Adenosine Triphosphate↗
PubMed1996

Distinct circulation patterns in peripheral blood of leukocyte subpopulations during the first 24 hours following autologous bone marrow transplantation.

We have studied the recirculation patterns of leukocyte subpopulations during the first 24 h at 5 min before and 5, 15, 180, and 1440 min after autologous bone marrow transplantation (ABMT) in 14 patients with cancer (6 with AML, 5 with malignant lymphomas, 2 with ALL, and 1 with Ewing's sarcoma) using multiparameter flow cytometry and measurements of myeloid progenitors (CFU-GM). Although the great majority of the injected cell populations were undetectable 5 min after graft infusion, the number of CD3+ T lymphocytes increased at 5 and 15 min and again at 24 h post-ABMT. In contrast, the number of CD56+ natural killer (NK) cells decreased rapidly after ABMT to remain low throughout the observation period. Mature myeloid and monocytic cells (identified by their expression of CD66 and CD14, respectively) were present before, as well as after ABMT in numbers indicating that they were probably of endogenous origin. Immature myeloid cells were identified in a three-color flow cytometric assay as CD13+ CD14- CD66- and tended to increase during the first 15 min after ABMT. Finally, when CFU-GM were followed longitudinally, they were found to be practically absent before ABMT but were clearly detectable in 12 of 14 patients throughout the observation period. We conclude that leukocyte subsets exhibit different recirculation patterns after ABMT, and in light of the increased knowledge about leukocyte-endothelial interactions, these data could provide a platform for attempts to control leukocyte recirculation during stem cell infusion.

Adolescent↗
PubMed1996

Physical responses to different modes of interval exercise in patients with chronic heart failure--application to exercise training.

METHOD: In exercise training with chronic heart failure patients, working muscles should be stressed with high intensity stimuli without causing cardiac overstraining. This is possible using interval method exercise. In this study, three interval exercise modes with different ratios of work/ recovery phases (30/60 s, 15/60 s and 10/60 s) and different work rates were compared during cycle ergometer exercise in heart failure patients. Work rate for the three interval modes was 50% (30/60 s), 70% (15/60 s) and 80% (10/60 s) of the maximum achieved during a steep ramp test (increments of 25 w/10 s) corresponding to 71, 98 and 111 watts on average. Metabolic and cardiac responses to the three interval exercises were then examined including catecholamine levels and perceived exertion. Parameters measured during interval exercise were compared with an intensity level of 75% peak VO2, determined during an ordinary ramp exercise test (increments of 12.5 W.min-1). RESULTS: (mean +/- SEM) (1) In all three interval modes, VO2, ventilation and lactate did not increase significantly during the course of exercise. Mean values during the last work phase were between 754 +/- 30 and 803 +/- 46 ml.min-1 for VO2, between 26 +/- 3 and 28 +/- 1 l.min-1 for ventilation and between 1.24 +/- 0.14 and 1.29 +/- 0.10 mmol.l-1 for lactate. (2) In mode 10/60 s, heart rate and systolic blood pressure increased significantly (82 +/- 4 --> 85 +/- 4 beats.min-1; 124 +/- 5 --> 134 +/- 5 mmHg; P < 0.05 each), while in mode 15/60 s catecholamines increased significantly (norepinephrine 0.804 +/- 0.089 --> 1.135 +/- 0.094 nmol.l-1; P < 0.008; epinephrine 0.136 +/- 0.012 --> 0.193 +/- 0.019 nmol.l-1; P < 0.005). (3) In all three modes, rating of leg fatigue and dyspnoea increased significantly during exercise but remained within the range of values considered 'very light to fairly light' on the Borg scale. (4) Compared to an intensity level of 75% peak VO2, work rate during interval work phases was between 143 and 221%, while cardiac stress (rate-pressure product) was significantly lower (83-88%). CONCLUSION: All three interval modes resulted in physical response in an acceptable range of values, and thus can be recommended.

Chronic Disease↗
PubMed1996

Influence of different exercise protocols on functional capacity and symptoms in patients with chronic heart failure.

This study compares hemodynamic, metabolic, and gas exchange responses, catecholamine levels, and symptoms in 35 male patients with chronic heart failure (CHF) ([mean +/- SD] age 53 +/- 11 yr; ejection fraction 24 +/- 11%) during three differently graded exercise test protocols. On three consecutive days patients performed cycle ergometry supine, with prolonged steps (prol BE) and right heart catheterization, ramplike cycle ergometry sitting (ramp BE), and ramplike treadmill walking (TMW). As in routine clinical practice, the prol BE was terminated when pathologic central hemodynamics and/or increased symptomology occurred, and ramp BE and TMW due to increased symptomology and/or physician's decision. During prol BE at ventilatory threshold (VT) the VO2 (8.6 +/- 1.8 ml.kg-1.min-1) was lower than during ramp BE (9.3 +/- 2.1 ml.kg-1.min-1) (P < 0.017) and TMW (11.8 +/- 2.3 ml.kg-1.min-1) (P < 0.0001). Prol BE, ramp BE, and TMW also differed significantly with respect to ventilation (22 +/- 7 l.min-1; 26 +/- 6 l/min-1; 29 +/- 7 l.min-1; P < 0.01) and heart rate (100 +/- 15 beats.min-1; 103 +/- 18 beats.min-1; 110 +/- 16 beats.min-1; P < 0.017). No differences were found in lactate levels, catecholamine levels, and ratings of leg fatigue and dyspnea. At test termination, the peak VO2 during prol BE (100.8 +/- 3.3 ml.kg-1.min-1) was lower than during ramp BE (13.3 +/- 4.1 ml.kg-1.min-1) (P < 0.0001) and TMW (14.7 +/- 3.4 ml.kg-1.min-1) (P < 0.0001). Peak norepinephrine value during ramp BE (4.531 +/- 2.788 nmol.l-1) was higher than during prol BE (3.707 +/- 2.262 nmol.l-1) (P < 0.001). Among the three tests, no significant differences were found for peak values of heart rate, lactate, and ratings of dyspnea. Although the VO2.kg-1 at VT was significantly higher during ramp BE and TMW compared to prol BE (P < 0.001), the values expressed as a percent of peak VO2.kg-1 were significantly lower (70 +/- 4%; 72 +/- 6%; 79 +/- 3%; P < 0.017). A systematic effect on aerobic capacity with reduced peak values during ramp BE and TMW was demonstrated when test termination was based primarily on pathological findings of central hemodynamics from prol BE.

Adolescent↗