Biomedical subjects

J Frank

Publications and source records attributed to J Frank.

At least 19 recordsLinked to original sources

PubMed1992

[Monotherapy with the ACE-inhibitor ramipril or the calcium antagonist nitrendipine in essential hypertension].

Angiotensin-converting enzyme (ACE) inhibitors and calcium antagonists have, by reason of their potentially favourable pharmacological profile, become increasingly established in the treatment of hypertension in recent years. In a double-blind randomized study with an initial placebo phase, carried out by practising physicians and thus aimed at the "usual" practice patients with essential hypertension, we assessed (1) the antihypertensive effect and tolerability of an ACE inhibitor (ramipril, 5 mg/d) or a calcium antagonist (nitrendipine, 20 mg/d) given in a single daily dose, and (2) a possible age-dependent blood pressure (BP) effect of these therapies. In the 4 weeks' placebo phase, the two treatment groups were comparable as regards average age (49.6 and 49.4 years), age-range (27-67 and 25-64 years) and BP. Fifty-two patients completed the following 6 weeks' phase with active drug therapy. On ramipril (n = 26), the BP measured 24-25 hours after the last drug administration was reduced in the supine position from an average of 155/102 to 142/91 mmHg (mean reduction -10.1%) and in the upright position from 156/106 to 141/96 mmHg (-9.3%). Nitrendipine (n = 26) reduced the average BP from 155/102 to 147/94 mmHg (-6.8%) and from 155/106 to 146/99 mmHg (-6.6%) respectively. BP-lowering effects of both treatments were largely independent of age. Including the patients who discontinued the study prematurely because of side effects (1 on ramipril, 4 on nitrendipine), the "intention to treat analysis" shows BP normalization rates (diastolic < or = 90 mm Hg) of 55% (ramipril) and 30% (nitrendipine) respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Purification and partial characterization of a thermostable trithionate hydrolase from the acidophilic sulphur oxidizer Thiobacillus acidophilus.

Cell-free extracts of Thiobacillus acidophilus catalysed the quantitative conversion of trithionate (S3O6(2-) to thiosulphate and sulphate. A continuous assay for quantification of experimental results was based on the difference in absorbance between trithionate and thiosulphate at 220 nm. Trithionate hydrolase was purified to near homogeneity from cell-free extracts of T. acidophilus. The molecular masses of the native enzyme and the subunit were 99 kDa (gel filtration) and 34 kDa (SDS/PAGE). The purified enzyme has a pH optimum of 3.5-4.5 and a temperature optimum of 70 degrees C. Enzyme activity was stimulated by sulphate. The stimulation of the enzyme activity by sulphate was half maximal at a concentration of 0.23 M. The Km for trithionate is 70 microM at 30 degrees C and 270 microM at 70 degrees C. Enzyme activity was lost after 36 days at 0 degrees C, 27 days at 70 degrees C; but after 97 days at 30 degrees C, 40% of the initial activity was still present: The enzyme activity was inhibited by mercury chloride, N-ethylmaleimide, thiosulphate and tetrathionate. Tetrathionate S4O6(2-) was not hydrolysed by trithionate hydrolase.

Ammonium Sulfate↗

PubMed1992

Eukaryotic initiation factor 3 does not prevent association through physical blockage of the ribosomal subunit-subunit interface.

The "native" 40 S ribosomal subunit, in which the protein eukaryotic initiation factor 3 is bound to the 40 S small ribosomal subunit, has been reconstructed to 48 A resolution. Comparison with a previous three-dimensional reconstruction of the "derived" 40 S subunit lacking any non-ribosomal components reveals the attachment site and morphology of the factor. It is a large (approximately 165 to 170 A long), bilobed, elongate structure, attached to the back lobes of the 40 S subunit by two strand-like features. Significantly, the factor is oriented away from the 60 S-subunit-40 S-subunit interface surface of the 40 S particle, suggesting that its anti-association activity is not accomplished via simple physical blockage of that surface.

Animals↗

PubMed1992

The archaebacterial hypusine-containing protein. Structural features suggest common ancestry with eukaryotic translation initiation factor 5A.

The amino acid hypusine is formed by post-translational modification of a lysine residue in eukaryotes and archaebacteria but up to now only the eukaryotic translation initiation factor eIF-5A has been known to contain this unique component. We isolated and purified a hypusine-containing protein from the thermophilic archaebacterium Sulfolobus acidocaldarius. The mainly cytosolic protein comprised about 0.03% of the post-ribosomal supernatant protein. No other hypusine-containing protein could be detected in S. acidocaldarius. The molar ratio of hypusine/hypusine-containing protein was 1:1. SDS/PAGE showed a molecular mass of 16.8 kDa; a pI of 7.8 for the native protein resulted from IEF. The N-terminus was blocked. Four cyanogen bromide fragments were partially sequenced and used to derive two 17-base oligonucleotide probes. A 3-kb HindIII fragment of genomic DNA hybridizing with both probes was cloned. By sequencing of exonuclease III deletion clones an open reading frame of 405 nucleotides was found coding for a protein of 135 amino acids with a molecular mass of 15 kDa. It contained all cyanogen bromide sequences analysed. Sequence alignment revealed that seven of eight residues around Lys40 in the Sulfolobus hypusine-containing protein were identical to the nonapeptides centered by hypusine in the three eIF-5A proteins sequenced so far. The Edman procedure gave no phenylthiohydantoin derivative for this position. For a central region of 44 residues a sequence similarity of 54% between the archaebacterial and eukaryotic proteins was calculated; for the total sequence about 33% similarity resulted. In addition, there were a number of conservative changes. The unique lysine modification surrounded by a conserved sequence strongly suggests a common ancestry of archaebacterial hypusine-containing protein and eIF-5A. Together with similarities in molecular mass and intracellular localization, it may point to an analogous biochemical function.

Amino Acid Sequence↗

PubMed1992

Three-dimensional reconstruction of single particles negatively stained or in vitreous ice.

The random-conical reconstruction method has been highly successful in three-dimensional imaging of macromolecules under low-dose conditions. This article summarizes the different steps of this technique as applied to molecules prepared with negative staining or vitreous ice, and sketches out the current directions of development. We anticipate that by using new instrumental developments, transfer function correction and computational refinement techniques, a resolution in the range of 7-10 A could ultimately be achieved.

Calcium Channels↗

PubMed1992

Do coronary heart disease risk factors measured in the elderly have the same predictive roles as in the middle aged. Comparisons of relative and attributable risks.

Risk factors for the 12-year incidence of definite coronary heart disease (CHD) among 3440 men who were middle-aged (51 to 59 years old) and 1419 men who were elderly (65 to 74 years old) at baseline examination were examined for differences in predictive values in terms of both relative risk and attributable (excess) risk of the highest versus the lowest quartile or appropriate categories. In multivariate models using Cox life-table regression procedures, serum cholesterol level, cigarette smoking, systolic blood pressure, and history of treatment for diabetes were significant predictors of incident CHD for both age groups. Alcohol consumption when modeled as drinker versus nondrinker showed a protective effect in both younger and older men. There was no dose relationship, however, among elderly drinkers. While the relative risks for the variables studied were similar between the two age groups, the excess risk was typically between 1.5 to 2.0 times higher for the older than the middle-aged men. In contrast, the detrimental effect of adiposity as measured by body mass index appeared to decline after age 65 for both measures of risk. This may partly be attributed to diminished adiposity overall in the older age group. The implications of these results are that serum cholesterol level, smoking, hypertension, diabetes, and possibly alcohol consumption continue to be important predictors for CHD when measured after age 65, and that the public health impact of these risk factors, in terms of excess risk, may be more important in the elderly.

Age Factors↗

PubMed1992

Cryo-EM of the native structure of the calcium release channel/ryanodine receptor from sarcoplasmic reticulum.

The native structure of the calcium release channel (ryanodine receptor) from rabbit skeletal muscle has been analyzed in two dimensions from electron micrographs of frozen hydrated specimens. Within a resolution of 3.0 nm there is excellent agreement between the structure as seen in vitreous water and in negative stained specimens. Features seen in the three-dimensional reconstruction of the negatively stained channel can be identified in the projection of the unstained receptor.

Animals↗

PubMed1992

Standardized noninvasive assessment of myocardial free fatty acid kinetics by means of 15-(p-iodo-phenyl) pentadecanoic acid (123I-pPPA) scintigraphy: II. Clinical results.

Our results establish that myocardial regions supplied by a significantly stenosed coronary vessel can be distinguished with high statistical significance from healthy regions on account of changes in the myocardium/background ratio, i.e. a reduction of regional uptake of 15-(p-iodo-phenyl) pentadecanoic acid (pPPA). The statistical significance applies to patients with coronary artery disease (CAD), to all examined CAD areas without areas of infarction as well as to infarcted regions. Our results also confirm the suitability of labelled fatty acids, such as pPPA, for the visualization of damaged myocardial regions. The results further indicate that pPPA practically is of comparable value to 201Tl with regard to their respective qualities as 'static' imaging agents for the heart muscle. This study, with the help of a simultaneous analysis of regional myocardial perfusion rates (rMBF) and of a parameter for the metabolism of fatty acids, practised here for the first time, could demonstrate interindividual differences between patients and groups of patients with a correlation between perfusion and the utilization of pPPA in patients with CAD. The reciprocal of the rMBF, the mean transit time (MTT), was significantly prolonged after stress in patients with CAD (P less than 0.05), suggesting impaired 'microcirculation' in the patient group. The determination of elimination half-lives (T1/2) contributes little if any information towards delineation of cardiac disease entities. The wide overlap of T1/2 values between various clinical syndromes and entities with extreme standard deviations remained an annoying problem in our studies. Nevertheless, certain trends in T1/2 behaviour could be recorded, but they did not yield any statistical significances, because of the high degree of individual variability. A considerable variability of T1/2 values among healthy controls was recorded as well as intra-individually in different regions of the heart muscle. The wide range of 'normal' values rendered statistical evaluation almost, if not entirely, impossible. It appears that the high degree of variability results amongst others, from technical shortcomings in the external recording instruments, i.e. gamma cameras, as well as from the presence of interfering alternate substrates such as glucose and lactate. Nevertheless, the wide range of measured results in healthy control subjects suggests the presence of a considerable regional intra-individual heterogeneity of cardiac substrate metabolism. One must therefore accept, at least in our opinion, that T1/2 values are not sufficiently reliable as an indicator of myocardial metabolism and are of little value with respect to clinical diagnostic considerations and to prognosis as well. Possible explanations for this finding are offered and discussed in this paper.

Adult↗

PubMed1992

A 360 degrees single-axis tilt stage for the high-voltage electron microscope.

A new type of specimen stage that permits more than 180 degrees of tilting about the axis of a side-entry rod has been developed for a high-voltage electron microscope (HVEM). Roughly cylindrical specimens, with radial dimensions of less than a few micrometers, that can be mounted on the tip of a microneedle or micropipette are applicable. For glass micropipettes, the energy of the 1-MeV beam of the HVEM is sufficient to image specimens through both walls. The stage employs a spindle mechanism that holds these needles or micropipettes coaxial with the tilt axis, allowing the specimen to be rotated without restriction. This arrangement, along with the cylindrical form of the specimen, is an important development for single-axis tomography, because it permits a complete 180 degrees set of projections to be recorded. The angular accuracy of the stage was demonstrated to be within +/- 0.20 degrees, with a cumulative error of less than 1.0 degrees over a 180 degrees span. The new stage was tested using puffball spores mounted on a micropipette. A 180 degrees tilt series was recorded and processed to yield a tomographic three-dimensional reconstruction which was displayed both as a cross-sectional view perpendicular to the tilt axis, and as a shaded surface viewed from different directions. The same computations were repeated using subsets of the tilt series to assess the effect of various amounts of missing information. Visual inspection of a selected cross-section from these reconstructions indicated that limiting the angular range to 160 degrees produced results nearly as good as the full data set. Limiting the range to 140 degrees, however, produced a noticeable geometric distortion, which became increasingly severe with ranges of 120 degrees and 100 degrees.

Image Interpretation, Computer-Assisted↗

PubMed1992

The role of interstitial cells in the progression of renal diseases.

Renal interstitial fibrosis (RIF) is frequently associated with distinct inflammatory and noninflammatory glomerular diseases. RIF is mainly responsible for a decline of excretory renal function and therefore influences the prognosis of several renal diseases. The resident interstitial cells of the kidney, which play a major role in causing RIF, are different renal fibroblasts, which respond to a variety of cytokines released by various cell types. Immunohistochemical analysis of human renal biopsies with different glomerulopathies revealed that CD2+ T lymphocytes are the major cells infiltrating the renal interstitium. In most forms of glomerulonephritis accompanied by interstitial inflammation, an abnormal expression of HLA-DQ/HLA-DP antigens, often associated with an aberrant expression of the intercellular adhesion molecule 1, was observed on proximal tubular epithelial cells, indicating that these cells may play an important role in local immune responses and probably function as antigen-presenting cells. Furthermore, it has been shown by Northern blot analysis that renal epithelial cells in culture express interleukin 6, platelet-derived growth factor and granulocyte-macrophage colony stimulating factor. Cell cultures established from renal biopsies revealed the presence of the three mitotic fibroblast types (MF I through MF III) and the three postmitotic types (PMF IV through PMF VI). The frequencies of the various progenitor fibroblasts MF I, MF II, and MF III differed significantly in cultures established from kidneys with (FKIF cells) and without RIF (NKF cells). In comparison to NKF cells, FKIF cells are characterized by the expression of a "new" protein, called "FIBROSIN," which seems to be specific for FKIF cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Division↗

PubMed1992

Acidic fibroblast growth factor accelerates dermal wound healing.

Acidic fibroblast growth factor (aFGF) is a potent mitogen in vitro for many cells of ectodermal and mesodermal embryonic origin including skin-derived epidermal keratinocytes, dermal fibroblasts and vascular endothelial cells. Based on the mitogenic activity for these skin-derived cells, we tested the ability of topically applied aFGF to promote healing of full-thickness dermal wounds in healthy rodents. Low doses of aFGF can produce almost a two-fold maximum acceleration in the rate of closure of full-thickness dermal punch biopsy wounds in young healthy mice and rats. The mitogen also produces a 3 to 4 day acceleration in the time to complete closure in rats. Quantitative histomorphometric analysis of wound tissue shows that aFGF induces a marked stimulation of angiogenesis, granulation tissue formation and the growth of new epithelium, but does not promote dermal contraction. Application of aFGF to linear incisions in rat skin produces a transient increase in wound tensile strength accompanied by enhanced cellularity and deposition of collagen. Therefore, aFGF functions as a pharmacological agent that can accelerate dermal wound healing in rodents and could act therapeutically to promote dermal tissue repair in humans.

3T3 Cells↗

PubMed1992

Alignment, classification, and three-dimensional reconstruction of single particles embedded in ice.

Cryo-electron microscopy of single biological particles poses new challenges to digital image processing due to the low signal-to-noise ratio of the data. New tools have been devised to deal with important aspects of 3-D reconstruction following the random-conical data collection scheme: (a) a new shift-invariant function has been derived, which promises to facilitate alignment and classification of single particle projections; (b) a new method of orientation search is proposed, which makes it possible to relate random-conical data sets to one another prior to reconstruction; and (c) the foundation is laid for a 3-D variance estimation which utilizes the oversampling of 3-D angular space by projections in the random-conical reconstruction scheme.

Algorithms↗

PubMed1992

[Measuring model for intraoperative determination of vascular resistance in crural vascular surgery].

The measurement of the vascular outflow resistance during reconstructive vascular operations was applied since 1989 on 45 subjects with reliable results. This measurement is an aid for decision of additional treatment increasing the outflow, like a jump- or sequential bypass or a pharmacological therapy. The principle of measurement is based on the injection of a known volume of saline in the vessel and the integration of the intravascular pressure during this injection. In the prototype used, the pressure integration was performed by means of a modified analog/digital conversion method, hereby the results could be achieved directly as numerical values. Further an automatic, microcomputer based implementation of the outflow resistance measurement, showed remarkable improvements of accuracy in laboratory tests.

Foot↗

PubMed1992

[Effect of vascular resistance on results in crural artery surgery].

Between February 1989 and June 1991 the peripheral outflow resistance was measured at 45 patients during infragenual bypass surgery. In order to find out whether there is a correlation between successful bypass grafting and measured outflow resistance, all patients were controlled regularly. There was a significant difference in mean resistance between those grafts remaining patent and those that failed. 8 out of 11 bypasses, that failed up to one month after operation, had measured peripheral resistance higher than 1.1 mmHg x min/ml. 12 out of 15 bypass grafts remained patent for more than one month and had an outflow resistance less than 0.55 mmHg x min/ml. There is no definite correlation between a measured outflow resistance from 0.55 to 1.1 mmHg x min/ml because of the low number of patients in this group. The purpose of resistance measurement during peripheral vascular surgery was to determine a final value for a decision, if additional surgical or non surgical treatment for a better runoff is necessary. In our study this value is 1.1 mmHg x min/ml. Additional treatments are the peripheral AV-fistula and a jump- or sequential-graft. Another possibility is the intra- and postoperative application of Prostaglandin, which is in an experimental study in our clinic.

Aged↗

PubMed1992

Three-dimensional reconstruction of single particles embedded in ice.

Single particles embedded in ice pose new challenges for image processing because of the intrinsically low signal-to-noise ratio of such particles in electron micrographs. We have developed new techniques that address some of these problems and have applied these techniques to electron micrographs of the Escherichia coli ribosome. Data collection and reconstruction follow the protocol of the random-conical technique of Radermacher et al. [J. Microscopy 146 (1987) 113]. A reference-free alignment algorithm has been developed to overcome the propensity of reference-based algorithms to reinforce the reference motif in very noisy situations. In addition, an iterative 3D reconstruction method based on a chi-square minimization constraint has been developed and tested. This algorithm tends to reduce the effects of the missing angular range on the reconstruction, thereby facilitating the merging of random-conical data sets obtained from differently oriented particles.

Algorithms↗

PubMed1992

Ofloxacin in human serum, urine, and tear film after topical application.

We evaluated the systemic absorption of ofloxacin eyedrops in humans and their availability in the tear film. Serum, urine, and tear film concentrations of ofloxacin were measured in 30 healthy women topically treated with 0.3% ofloxacin, in both eyes, four times daily for 10 1/2 days. Serum was collected before the first daily dose on days 1 and 11 and at 18 time points before the second dose. Maximum serum ofloxacin concentrations (1.89 +/- 1.13 ng/ml) after 10 1/2 days of topical dosing were more than 1,000 times lower than those reported after standard oral doses of 300 mg ofloxacin. Urine was collected for the 24-h period after the first daily dose on days 1 and 10. Topical ofloxacin was excreted in the urine primarily in unmodified form and recovery rates were significantly higher on day 10 (76.1 +/- 41.5%) than on day 1 (56.6 +/- 31.6%) (p less than 0.05). Both serum and urine data give evidence to accumulations of ofloxacin over a 10 1/2-day period. The low serum concentration at steady state suggests an extremely low potential for producing systemic effects. No systemic side effects attributable to topical ofloxacin were observed. Mild ocular irritation was reported by two patients while under treatment. Tears were collected 4 h after the first treatment on day 11 and at 5, 10, 20, 30, and 40 min after the second treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗

PubMed1991

Echo-planar time course MRI of cat brain oxygenation changes.

When deoxygenated, blood behaves as an effective susceptibility contrast agent. Changes in brain oxygenation can be monitored using gradient-echo echo-planar imaging. With this technique, difference images also demonstrate that blood oxygenation is increased during periods of recovery from respiratory challenge.

Animals↗

PubMed1991

Psychosocial impacts in populations exposed to solid waste facilities.

This interdisciplinary study uses a parallel case study design to investigate psychosocial impacts in populations exposed to three solid waste facilities in Southern Ontario. Impacts are examined at three social scales: individual, social network and community levels. The objectives and design derive from a feasibility study recently completed by the same research team. A two stage approach is adopted. The first is an epidemiologic survey to determine the prevalence of psychosocial impacts in the populations within a prescribed area around each site. A disproportionate stratified (by distance) random sample of 250 households is surveyed at each site. Data on awareness, knowledge, concern and action regarding the site are also obtained. Scores on pre-validated health measurement scales will be compared with population norms to determine the frequency distribution above, within and below the range of normal. The second stage involves the use of qualitative methodologies to provide an in-depth analysis of the individual, social network and community level factors affecting psychosocial impacts and reactions to the situation. Depth interviews with a sub-sample of survey respondents explore individual perceptions, attitudes and actions. Focus groups composed of members of relevant organizations and discussion groups comprising non-members uncover social network and community perspectives in an interactional setting. Interviews and group sessions are taped and transcribed for content analysis of salient themes. Textual analysis of media reports and other relevant documentation provide insights regarding the informational environment and the community context of the issues.

Adaptation, Psychological↗