Superior cervical ganglionectomy in monkeys: effects on refraction and intraocular pressure.
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Animals↗
Biomedical subjects
K Schmidt
Publications and source records attributed to K Schmidt.
Quantification of intracellular metabolic fluxes from fractional enrichment and 13C-13C coupling constraints on the isotopomer distribution in labeled biomass components.
A method for the quantification of intracellular metabolic flux distributions from steady-state mass balance constraints and from the constraints posed by the measured 13C labeling state of biomass components is presented. Two-dimensional NMR spectroscopy is used to analyze the labeling state of cell protein hydrolysate and cell wall components. No separation of the biomass hydrolysate is required to measure the degree of 13C-13C coupling and the fractional 13C enrichment in various carbon atom positions. A mixture of [1-13C]glucose and uniformly labeled [13C6]glucose is applied to make fractional 13C enrichment data and measurements of the degree of 13C-13C coupling informative with respect to the intracellular flux distribution. Simulation models that calculate the complete isotopomer distribution in biomass components on the basis of isotopomer mapping matrices are used for the estimation of intracellular fluxes by least-squares minimization. The statistical quality of the estimated intracellular flux distributions is assessed by Monte Carlo methods. Principal component analysis is performed on the outcome of the Monte Carlo procedure to identify groups of fluxes that contribute major parts to the total variance in the multiple flux estimations. The methods described are applied to a steady-state culture of a glucoamylase-producing recombinant Aspergillus niger strain.
Aspergillus niger↗
[Outcome of a four-week ambulatory cardiac rehabilitation (phase II) on cardiovascular risk factors, physical fitness and occupational reintegration in patients after myocardial infarct, dilatation treatment and heart operation].
From October 1994 to July 1996, 128 patients (30 women, 98 men) participated in an outpatient cardiac rehabilitation program (phase II). Our objectives were to demonstrate risk-factor modification and increased workload capacity resulting directly from the rehabilitation in terms of primary results and long-term effects 6 and 12 months (n = 118, Figure 1) respectively 1.5 and 2 years (n = 87) after termination of the program (Tables 9 to 12). We observed how many of the patients were able to be occupationally reintegrated after completion of phase-II rehabilitation. Workload capacity significantly increased from 1.2 W/kg upon entry to 1.5 W/kg (p < or = 0.05) upon completion of 4 weeks cardiac rehabilitation. Workload capacity remained consistently high at 6 months and 1 year (1.5 W/kg) and at 1.5 and 2 years (1.7 W/kg). Total cholesterol decreased significantly from 247 to 201 mg/dl (p < or = 0.05) during the 4-week program. Significant cholesterol (p < or = 0.01) reductions persisted at 6 months (216 mg/dl) and 1 year (215 mg/dl). After 1.5 and 2 years, the total cholesterol was less than 14% and 17% below the mean of cholesterol at the beginning of the program. Similarly, LDL cholesterol was 185 mg/dl before entering the program, 146 mg/dl after 4 weeks, 151 mg/dl after 6 months and 149 mg/dl after 1 year. Triglyceride levels showed a significant reduction (p < or = 0.01) with levels 189 mg/dl before entering the program, 148 mg/dl after 4 weeks, 151 mg/dl after 6 months and 154 mg/dl after 1 year. LDL cholesterol and triglyceride levels did not significantly increase after 1.5 and 2 years. The HDL cholesterol increased slightly as a long-term effect (from 51 mg/dl before entering the program to 55, 56 and 54 mg/dl after 1, 1.5 and 2 years, respectively). Seventy-three percent of the patients questioned (n = 73) found the program very good, 27% said it was good and no patient was dissatisfied. Fifty-one (81%) of the 63 patients who were actively employed before becoming ill and later entering our program were immediately able to be reintegrated into their previous occupation. In several cases reintegration took 7 weeks. Seven (11%) patients applied for pension, 5 (8%) patients remained unemployed on sick-leave.
Adult↗
Childhood medulloblastoma in Denmark 1960-1984. A population-based retrospective study.
Medulloblastoma is a common paediatric brain tumour, located in the cerebellum and in the IV ventricle, surpassed in frequency only by astrocytomas. 180 children below the age of 15 with a medulloblastoma of the posterior fossa were treated in Denmark in the 25-year period from 1960 to 1984 and followed up until the end of 1996, or until death. During the 25 years they accounted for 20% of all intracranial tumours in children in Denmark. All tumours were histologically verified. The mean annual incidence was 6.4x10(-6), decreasing slightly with a factor of 0.12x10(-6) per year. The male/female ratio was 2.1 - twice that of the background population of children (1.05). The 5-year survival rate following diagnosis, surgery and radiotherapy was 23%, and the 25-year survival rate was 16%. The 5-year survival rate was 8% in the first 5-year period of 1960-1964, increasing to 36% in the last period 1980-1984. Presumably the increase in survival depends on many factors, e.g. improved diagnostic methods and neuroanaesthesia, better operative technique (microscope), improvements in radiotherapy and the introduction of chemotherapy. The best predictive factors of a good prognosis were preoperative CSF shunting, radical tumour removal and complete radiotherapy, i.e. irradiation of the brain, tumour bed and spinal cord. The survival rate in the last five-year period was seven times higher than the survival rate found in a comparable Danish study from the years 1935-1959. Most of the children followed Collins law of risk index. The results of treatment in children with medulloblastoma remain unsatisfactory. Accordingly, participation in international prospective studies of multimodal treatment should be encouraged, possibly using chemotherapy prior to surgery.
Adolescent↗
Genetic analysis of large-sized RNA 2 species of a TCM-like tobacco rattle virus source from spinach.
RNA 2 of a tobacco rattle virus isolate from spinach (TRV SP) resembles that of a recently described isolate from onion (TRV ON), but its ORF 3 is much larger. Naturally infected spinach apparently contains a second TRV SP RNA 2 species with a partially deleted ORF 3 and an RNA 1-like 3'-end which consists of c. 1500 nts and thus is much longer than in any other tobravirus RNA 2 sequenced so far. RNAs 2 of TRV SP and ON are closely related to that of TRV TCM from tulip, but besides the additional ORF 3 they have longer 5'-UTRs with two GCAUA motifs and different coat protein C-termini. The high percentage of amino acid sequence identity in the coat proteins of the TCM-like tobraviruses suggests that they may be considered as strains of a distinct virus species. Possible pitfalls in the use of serology in tobravirus classification are discussed.
5' Untranslated Regions↗
Selective stimulation of L-arginine uptake contributes to shear stress-induced formation of nitric oxide.
The aim of this study was to investigate the kinetics of L-arginine transport mechanisms and the role of extracellular L-arginine in nitric oxide formation during shear stress activation of endothelial cells. Porcine aortic endothelial cells were grown to confluence and were exposed to various amounts of shear stress for 40 min. Formation of nitric oxide was monitored by measuring elevation of endothelial cGMP. Activity of amino acid transport systems was determined by measuring the uptake of L-[3H]leucine (L system) and L-[3H]arginine (y+) under resting and shear stress condition. Shear stress-mediated nitric oxide formation critically depended on the presence of extracellular L-arginine, which increased shear stress-induced cGMP increases in a concentration dependent manner (EC50=123 microM). In addition, shear stress increased L-arginine uptake, while the transport capacity for neutral amino acids (L system) remained unchanged under shear stress conditions. Analysis of the kinetics of the uptake of L-arginine under resting and shear stress conditions indicate that shear stress increased velocity of the high affinity, low capacity transport (y+) without affecting affinity of this system. These data suggest that shear stress selectively activates uptake of L-arginine in endothelial cells and that the uptake of L-arginine might be important for shear stress-mediated nitric oxide formation.
Adenosine Diphosphate↗
A simple and rapid method for preparation of viral DNA from cell associated cytomegalovirus.
In the field of human cytomegalovirus pathogenesis there is growing interest in analyzing recent clinical isolates rather than cell culture adapted laboratory strains. However, true low passage isolates are strictly cell associated prior to cell culture adaptation and only a minor fraction of cells are infected at low passage number. Both conditions hinder the preparation of pure viral DNA. To date, genetic analyses had been carried out mostly with supernatant associated cytomegalovirus. A rapid and simple method is described for preparation of viral DNA from low passage cell associated isolates with little cytopathogenic effect. The protocol is based on a combination of Triton X-100 lysis, nuclease treatment, and subsequent phenol chloroform extraction. Cellular background was reduced significantly to enable clear detection of all viral DNA fragments in restriction fragment length analysis. The method yielded DNA which was suitable for downstream applications like cloning of viral DNA fragments or transfection of genomic viral DNA. This method may facilitate genomic analyses of pathogenic cell associated recent cytomegalovirus isolates.
Cells, Cultured↗
Physiology and pathophysiology of senescence.
Average life-span and maximum life-span are the two basic parameters by which the processes of ageing and senescence of individuals of a species are characterized. Although each individual of a species if affected by both parameters can only be studied in populations of individuals. The survival curve of a cohort of individuals reflects the different influences of constitutional and environmental factors on life expectancy. The intrinsic molecular and cellular mechanisms by which the physiological process of ageing and senescence is controlled and regulated are far from being understood although a large number of hypotheses have emerged over the decades. Stochastic and deterministic models of the ageing process have been developed but a theory unifying the large body of experimental, epidemiological and clinical findings is still lacking. In this contribution a brief review is presented on the different hypotheses aiming at explaining the physiology and pathophysiology of ageing and senescence.
Adult↗
Preferential inhibition of inducible nitric oxide synthase in intact cells by the 4-amino analogue of tetrahydrobiopterin.
In the present study we demonstrate that the 4-amino analogue of tetrahydrobiopterin, 2,4-diamino-5,6,7,8-tetrahydro-6-(l-erythro-1, 2-dihydroxypropyl)pteridine (4-amino-H4biopterin) binds with high affinity to recombinant endothelial NO synthase and concomitantly inhibits enzyme activity [IC50 = 14.8 +/- 7.5 microm in the presence of added 5,6,7,8-tetrahydro-l-erythrobiopterin (H4biopterin) 10 microm] as efficiently as previously shown for inducible NO synthase [Mayer, B., Wu, C.Q., Gorren, A.C.F., Pfeiffer, S., Schmidt, K., Clark, P., Stuehr, D.J. & Werner, E.R. (1997) Biochemistry 36, 8422-8427]. In cultured porcine endothelial cells, however, 4-amino-H4biopterin was less effective in inhibiting NO formation (IC50 = 420 +/- 36 microm) as compared with inhibition of the inducible isoform in murine fibroblasts (IC50 = 15 +/- 4.9 microm) and in human DLD-1 adenocarcinoma cells (IC50 = 55 +/- 10.3 microm). In all cells investigated, the inhibitory effect of 4-amino-H4biopterin was markedly enhanced by depletion of intracellular H4biopterin and could be overcome by increasing intracellular H4biopterin concentrations. Endothelial cells contained lower amounts of H4biopterin [5.2 +/- 0.3 pmol.(mg protein)-1] than fibroblasts [19.4 +/- 2.7 pmol.(mg protein)-1] and DLD-1 cells [8.3 +/- 1.1 pmol.(mg protein)-1], so that the selectivity of 4-amino-H4biopterin towards inducible NO synthase was not explained by differences in the H4biopterin levels. Because 4-amino-H4biopterin did not suppress expression of NO synthase in cytokine-treated cells, we suggest that high-affinity binding of the inhibitor during protein expression may be responsible for the preferential inhibition of the inducible isozyme in intact cells.
Animals↗
The effect of the additional use of grommets in silicone implant arthroplasty of the metacarpophalangeal joints.
After silicone arthroplasty of the metacarpophalangeal (MP) joint there is increasing osteolysis, subsidence and fracture of the implants in the longer postoperative term. In 44 patients with rheumatoid arthritis (54 hands) 151 arthroplasties of the metacarpophalangeal joint were assessed at a mean of 3.9 years postoperatively. In 57 arthroplasties titanium protectors (grommets) were used. There were no significant differences in the clinical outcomes with respect to swelling, correction of ulnar deviation, range of active movement and grip strength. The additional use of grommets in MP joint arthroplasty slightly reduced reactive osteolysis, protected the spacers from breakage and slightly reduced the amount of pain with only a few additional complications in the midterm follow-up.
Activities of Daily Living↗
Ten-year follow-up of silicone arthroplasty of the metacarpophalangeal joints in rheumatoid hands.
In resection arthroplasty of destroyed metacarpophalangeal joints stabilisation with a silicone spacer is regarded as the gold standard. In 28 patients with rheumatoid arthritis (34 hands) 102 arthroplasties of the metacarpophalangeal joint were assessed a median of 10 years postoperatively (range 8.7-12.5). All patients reported pronounced subjective relief of pain, and in three quarters function of the hand had improved. The median active range of movement decreased from 40 degrees (range 10 degrees-90 degrees) preoperatively to 35 degrees (range 5 degrees-85 degrees) postoperatively. Ulnar deviation was corrected from a median of 35 degrees (range 0 degrees-60 degrees) preoperatively to 10 degrees (range 0 degrees-40 degrees) postoperatively. The extension deficit was improved from a median of 35 degrees (range 10 degrees-80 degrees) before surgery to a median of 10 degrees (range 0 degrees-30 degrees) at follow up. Grip strength remained unchanged. Radiological examination showed surrounding osteolysis in 89% of the implants and 28% had broken. The well-known discrepancy between fair clinical and good subjective results with distinct radiological findings such as osteolysis was therefore confirmed. Material fatigue and sharp bony edges that result from osteolysis may be the cause of the relatively common implant fractures and ulnar deviation in this long-term follow-up.
Arthritis, Rheumatoid↗
Which linear compartmental systems can be analyzed by spectral analysis of PET output data summed over all compartments?
General linear time-invariant compartmental systems were examined to determine which systems meet the conditions necessary for application of the spectral analysis technique to the sum of the concentrations in all compartments. Spectral analysis can be used to characterize the reversible and irreversible components of the system and to estimate the minimum number of compartments, but it applies only to systems in which the measured data can be expressed as a positively weighted sum of convolution integrals of the input function with an exponential function that has real-valued nonpositive decay constants. The conditions are met by compartmental systems that are strongly connected, have exchange of material with the environment confined to a single compartment, and do not contain cycles, i.e., there is no possibility for material to pass from one compartment through two or more compartments back to the initial compartment. Certain noncyclic systems with traps, systems with cycles that obey a specified loop condition, and noninterconnected collections of such systems also meet the conditions. Dynamic positron emission tomographic data obtained after injection of a radiotracer, the kinetics of which can be described by any model in the class of models identified here, can be appropriately analyzed with the spectral analysis technique.
Algorithms↗
Mentoring. Sharing our wisdom.
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Adaptation, Psychological↗
Modification of human cytomegalovirus tropism through propagation in vitro is associated with changes in the viral genome.
Following extensive propagation in fibroblasts, human cytomegalovirus (HCMV) loses tropism for a number of otherwise natural host cells, in particular, endothelial cells. In this study, the hypothesis was tested that loss of endothelial tropism is associated with the appearance of genomic variants. Initial quantitative focus expansion assays on endothelial monolayers demonstrated that, while the laboratory strains AD169 and Towne failed to form detectable foci, 29 out of 30 recent clinical HCMV isolates had the potential to expand in endothelial cell culture. By long-term adaptation in fibroblast cultures, nonendotheliotropic strains could be selected from clinical HCMV isolates, while long-term endothelial-adapted strains of the same isolates retained both fibroblast tropism and endothelial tropism. Such differentially adapted isolate pairs always displayed genomic differences in restriction fragment length analyses. Coinfection of endothelial cells by two nonendotheliotropic HCMV strains yielded an endotheliotropic recombinant HCMV variant combining portions of the genomes of both parental viruses. When DNA purified from various isolates was transfected into fibroblasts, progeny virus retained the specific tropism of parental virus from which the DNA was isolated. These findings demonstrate that endothelial tropism is an inherent property of most clinical HCMV isolates and is determined by the viral genome. Although the specific determinants of HCMV cell tropism are still unknown, this study provides the first evidence for a genetic contribution.
Cells, Cultured↗
M protein of a Streptococcus dysgalactiae human wound isolate shows multiple binding to different plasma proteins and shares epitopes with keratin and human cartilage.
Besides group A (GAS), Lancefield group C beta-haemolytic streptococci (GCS) have been implicated as a causative agent in outbreaks of purulent pharyngitis. In this study we have investigated a class CI M protein of a Streptococcus dysgalactiae1:256, revealed that 26% of these sera showed serological cross-reactivity between a 68-kDa cartilage protein and the N-terminal part of MC. Only 8% of the sera of healthy patients showed this property. In additional, MC also cross-reacted with antibodies recognising epidermal keratins. The cross-reacting 68-kDa protein from cartilage was different from human serum albumin, but was recognised with anti-vimentin immune serum. The MC was cloned and the gene sequenced. By using PCR, recombinant gene fragments encoding characteristic peptide fragments of MC were expressed in Escherichia coli. The peptides were used to map the binding sites for plasma proteins and to locate the cross-reacting epitopes on the MC molecule. In consequence, sequence alignments revealed that MC shared homologous regions with vimentin and different keratins. Our data, obtained with MC, suggest that not only infections with GAS but also infections with GCS and possibly GGS (the latter species can also produce class CI M-like proteins) may be responsible for the formation of streptococcal-associated sequel diseases.
Amino Acid Sequence↗
[Detection of quadratic phase coupling between EEG signal components by nonparamatric and parametric methods of bispectral analysis].
Recently the assumption of the independence of individual frequency components in a signal has been rejected, for example, for the EEG during defined physiological states such as sleep or sedation [9, 10]. Thus, the use of higher-order spectral analysis capable of detecting interrelations between individual signal components has proved useful. The aim of the present study was to investigate the quality of various non-parametric and parametric estimation algorithms using simulated as well as true physiological data. We employed standard algorithms available for the MATLAB. The results clearly show that parametric bispectral estimation is superior to non-parametric estimation in terms of the quality of peak localisation and the discrimination from other peaks.
Algorithms↗
Risk of low birthweight in social districts of Copenhagen.
The purpose of this survey was to investigate the small-area variations in low birthweight within social services districts in Copenhagen and the relation of such variations to the socioeconomic characteristics of the district. The study was based on register data and included all live-born single on births to women living in the city of Copenhagen from 1987-90. We found a statistically significant association between district and risk of newborns being small-for-gestational age (SGA). This association was independent of adjustment for maternal age and parity. Only part of the association was explained, though this was still significant, using an index summarizing the socioeconomic living conditions in the district. Splitting up the index into its four constituent components, however, showed that the association between SGA and district was primarily due to housing conditions in the districts. Mapping the districts demonstrated a clear tendency of clustering of the high-risk areas with poor socioeconomic conditions.
Cluster Analysis↗
[Arterial reconstruction in arteriopathic diabetic perforating ulcer--is it effective? Revascularization in diabetes mellitus and peripheral arterial occlusive disease].
OBJECTIVE: In the present study long-term patency and limb-salvage rates of femoro-distal bypasses were compared for patients suffering from PAOD stage III and IV with and without DM. METHODS: Between 1990 and 1994, some 192 femoro-crural bypass procedures were performed; 132 reconstructions were carried out on patients with PAOD, 60 bypasses on patients with PAOD and DM. The two groups did not differ significantly regarding age, gender and risk pattern. RESULTS: The comparison of the two groups showed a significant advantage for the diabetic patients regarding the limb-salvage rate. In both groups there was also a significant difference regarding patency in favour of the diabetics. CONCLUSION: Patients suffering from DM and PAOD profit from femoro-distal bypasses. An aggressive vasosurgical reconstructive therapy is indicated for these patients.
Aged↗