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Biomedical subjects

H Weber

Publications and source records attributed to H Weber.

At least 19 recordsLinked to original sources

Cardiac involvement in systemic sclerosis.

OBJECTIVE: To assess the incidence and extent of cardiac involvement in systemic sclerosis (SSc) patients with no apparent cardiac symptoms. METHODS: Surface electrocardiography, ambulatory electrocardiography, radionuclide ventriculography, myocardial scintigraphy, and echocardiography were performed in 18 patients. RESULTS: These studies demonstrated ventricular tachycardia in 1 patient, nonsustained ventricular tachycardia in 5, supraventricular tachycardia in 6, decreased left ventricular ejection fraction in 2, decreased right ventricular ejection fraction in 8, and stress-induced reversible myocardial perfusion abnormalities in 6. CONCLUSION: These observations demonstrate a high rate of cardiac abnormalities in SSc patients without cardiac symptoms.

Aged

Characterization of mutants of the yeast Yarrowia lipolytica defective in acetyl-coenzyme A synthetase.

The expression of the glyoxylate cycle enzymes is required for growth of the yeast Yarrowia lipolytica on acetate or fatty acids as sole carbon source. Acetyl-coenzyme A, which is produced by acetyl-coenzyme A synthetase (ACS) from acetate, is needed for induction of this expression. Acetate-non-utilizing mutants of this yeast were investigated in order to identify mutants which express no or strongly reduced activity of this enzyme. Mutations in gene ICL2 exhibited the strongest effects on the activity. In icl2 mutants, lack of ACS activity resulted in a non-induced glyoxylate cycle on acetate; however, induction on fatty acids was not affected. Gene ICL2 was identified as the structural gene encoding the monomer of ACS. It is shown that a high level of ACS activity is necessary for full expression of the glyoxylate cycle enzymes. Mutations in gene ICL1, which encodes isocitrate lyase, resulted in overproduction of ACS without any growth on acetate. A new gene (GPR1 = glyoxylate pathway regulation) was detected in which trans-dominant mutations inhibit expression of ACS and the glyoxylate cycle on acetate as carbon source.

Acetate-CoA Ligase

Characteristics of "anti" saccades in man.

Four subjects - all made large numbers of Express saccades in the normal gap task - were instructed to make saccades in the direction opposite to the side where a visual stimulus appeared ("anti" task). Gap and overlap trials were used. Saccadic reaction time (SRT), velocity and amplitude of the corresponding eye movements were analysed and compared to those of saccades made in the normal task. The velocity of "anti saccades" was found to be slightly (up to 15%) but significantly slower in two subjects. The distributions of SRTs in normal gap tasks show a small group of anticipatory saccades (with SRT below 80 ms and slower velocities) followed by a group of saccades with fast reaction times between 80 ms and 120 ms (Express saccades) followed by another large group ranging up to 180 ms (regular saccades). In the gap anti task there are anticipatory saccades and saccades with SRTs above 100 ms; Express saccades are missing. The distribution of SRTs obtained in the overlap anti task was unimodal with a mean value of 231 ms as compared to 216 ms in the normal task. The introduction of the gap therefore clearly decreases the reaction times of the anti saccades. Control experiments show that the delay of anti saccades is not due to an interhemispheric transfer time but must be attributed to the saccade generating system taking more time to program a saccade to a position where no visual stimulus appears. These data are discussed as providing further evidence for the existence of a reflex-like pathway connecting the retina to the oculomotor nuclei mediating the Express saccade.

Humans

Dead zone for express saccades.

The saccadic eye movements of three humans and one non-human primate (a male rhesus monkey) have been measured for target eccentricities between 0.3 and 15 deg. With a gap task (fixation point offset precedes target onset by 200 ms) and a target at 4 deg, all subjects produced reasonable amounts of express saccades as indicated by a clear peak in the distribution of their saccadic reaction times (SRT): about 100 ms in human subjects and 70 ms in the monkey. This peak disappeared with decreasing target eccentricity below 2 deg, but saccades of longer (regular) reaction times were still present. Thus it was found that there exists a dead zone for express saccades. In addition, small saccades have a much stronger tendency to overshoot the target and their velocity falls above the main sequence as defined by the least square fit of an exponential v = vo(1-exp(-a/ao)) to the maximal velocity (v) versus amplitude (a) relationship (vo and ao are constants fitted). It is concluded that for small saccades the express way is blocked functionally or does not exist anatomically.

Animals

Cloning of the mating-type gene MATA of the yeast Yarrowia lipolytica.

The mating type gene MATA of the dimorphic yeast Yarrowia lipolytica was cloned. The strategy used was based on the presumed function of this gene in the induction of sporulation. A diploid strain homozygous for the mating type B was transformed with an integrative gene bank from an A wild-type strain. A sporulating transformant was isolated, which contained a plasmid with an 11.6 kb insert. This sequence was rescued from the chromosomal DNA of the transformant and deletion mapping was performed to localize the MAT insert. The MAT gene conferred both sporulating and non-mating phenotypes on a B/B diploid. A LEU2 sequence targeted to this locus segregated like a mating type-linked gene. The A strain did not contain silent copies of the MAT gene.

Chromosome Deletion

Neuroendocrine effects of ipsapirone on the hypothalamic-pituitary adrenal axis: CRF, ACTH and cortisol in healthy volunteers.

The neuroendocrine effects (changes in plasma CRF, ACTH and cortisol) of single and multiple (t.d.s. for 2 days) doses of ipsapirone (BAY Q 7821) 5 and 10 mg have been investigated in 6 healthy male volunteers. The study followed a balanced complete block, placebo-controlled and double blind design with two baseline phases (pre and post-treatment). Volunteers were investigated on identical days during 5 successive weeks. The results do not show a specific effect of ipsapirone on the hypothalamic-pituitary-adrenal axis when doses in the range of 5-30 mg per day were given.

Adrenocorticotropic Hormone

Technique and results of vascular endoscopy in arterial and venous reconstructions.

In an effort to maximize results, vascular endoscopy was used in our institution to monitor arterial and venous reconstructions. Since 1982, angioscopy was applied as a control method in 182 venous thrombectomies to treat iliofemoral thrombosis and 114 aortoiliac thromboendarterectomies. Of the cases with venous thrombectomy reviewed, 50% were incomplete by endoscopic evidence; of these, in 80% the remaining clots could be partly or completely removed. Additionally, in six patients a venous spur was found. Of 114 attempted aortoiliac thromboendarterectomies, only 91 could be completed. In the remainder, endoscopic evidence of persistent intimal flaps forced us to bypass the affected segments. With further miniaturization of the angioscopes, the method was also applied to check vessel repair on small-caliber arteries. In an initial study with 220 femorodistal bypasses we were unable to find a statistically significant difference of primary patency in grafts that were endoscopically controlled or not. In the learning phase with the in situ technique, we identified competent valve remnants in 40%, but this rate could be reduced to 12.7% with growing experience in valvulotomy. We conclude from our data that angioscopy is very helpful in assessing the morphological integrity of aortoiliac thromboendarterectomies and venous thrombectomies. The actual value in infrainguinal arterial reconstructions still remains to be proven.

Angioscopy

Joint replacement components made of hot-forged and surface-treated Ti-6Al-7Nb alloy.

We have developed a titanium-aluminium alloy with the inert alloying element niobium. The optimal composition was found to be Ti-6Al-7Nb (Protasul-100). This custom-made alloy designed for implants shows the same alpha/beta structure as Ti-6Al-4V and exhibits equally good mechanical properties. The corrosion resistance of Ti-6Al-7Nb in sodium chloride solution is equivalent to that of pure titanium and Ti-6Al-4V. This is due to a very dense and stable passive layer. Highly stressed anchorage stems of different hip prosthesis designs have been made from hot-forged Ti-6Al-7Nb. The polished surfaces of hip, knee and wrist joints made of Ti-6Al-7Nb and articulating against polyethylene are surface-treated by means of a very hard and 3-5 microns thick titanium nitride coating (Tribosul-TiN) or by oxygen diffusion hardening (Tribosul-ODH) to a depth of 30 microns.

Humans

Saccadic reaction times in patients with frontal and parietal lesions.

The effect of unilateral circumscribed lesions in different areas of the frontal and parietal cortex on the distributions of saccadic reaction times (SRTs) was investigated in 32 patients under four stimulus conditions: (i) gap-random: a target light appeared 200 ms after extinction of a central fixation light randomly at 8 degrees either left or right; (ii) overlap-random: like (i), but the fixation light remained on ('overlap'); (iii) gap-simultaneous: two peripheral lights appeared simultaneously left and right 200 ms after the extinction of the fixation light, one predesignated by instruction as saccadic target; (iv) overlap-simultaneous: like (iii), but the fixation light remained on. Depending on SRT and condition and based on the data of control subjects, we evaluated the percentages of anticipatory (SRT: 0-90 ms), express (91-157 ms) and regular (158-400 ms) saccades, of time (> 400 ms) and direction errors as well as the mean latencies and the standard deviations. These data were compared across control subjects, frontal lobe patients with a lesion in the region of the frontal eye field (FEF), and frontal patients with a lesion outside the FEF, as well as across control subjects, parietal lobe patients with a lesion in the dorsolateral region, and parietal patients with a lesion outside the dorsolateral region. (i) Frontal patients with a lesion in the FEF region showed an increased percentage of express saccades (gap-random condition), especially with saccades directed towards the side of the lesion (ipsilateral). If fixation was not interrupted prior to target appearance (overlap-random), express saccades were largely suppressed, similar to normals. All patients with a frontal lesion, whether in the region of the FEF or not, showed a decreased percentage of contralateral anticipatory saccades (gap-simultaneous), whereas the percentages of direction and time errors were in the normal range, even if more than one stimulus was presented (e.g. overlap-simultaneous condition). (ii) Patients with dorsolateral parietal lesions showed decomposed SRT patterns (high SRT variability, increased percentages of time and direction errors, decreased percentages of express and anticipatory saccades). The decomposition had a contralateral preponderance and increased if more than one stimulus was visible beside the saccadic target. Our results suggest that FEF lesions impair mainly the volitional control over visually triggered express or reflex-like saccades if fixation is disrupted, whereas dorsolateral parietal lesions impair mainly the selection of the visual targets.

Adult

Prognostic value of heart rate variability in patients awaiting cardiac transplantation.

Time and frequency domain parameters of heart rate variability (HRV) were determined in patients with severe endstage heart failure awaiting cardiac transplantation (HTX). These parameters were then correlated with mortality to investigate the performance of HRV in discriminating between groups with high and low risk of death. The standard deviation of five consecutive RR intervals (SDANN) was found to be the parameter with the greatest sensitivity (90%) and specificity (91%). Patients with SDANN values of < 55 msec had a twenty-fold increased risk of death (90% confidence limits: 4-118, P < 0.001). The results furthermore suggest that measurements of HRV are superior to other prognostic markers such as left ventricular ejection fraction, pulmonary artery wedge pressure, cardiac index, and serum sodium levels. We conclude that HRV is a powerful, noninvasive tool to assess the risk of death in candidates for HTX. HRV measurements can therefore be used as a supplement to other markers of risk to determine the optimal therapeutic strategy in patients with severe congestive heart failure.

Adult

A cDNA clone of tomato mosaic virus is infectious in plants.

A cDNA clone of tomato mosaic virus (ToMV) genomic RNA was fused to the cauliflower mosaic virus 35S RNA promoter and the nopaline synthase gene polyadenylation signal. The transcriptional initiation site of the 35S RNA promoter was altered by in vitro mutagenesis so that the resulting transcripts start at the first nucleotide of the ToMV sequence. In addition, 12 nucleotides were inserted in the 5' untranslated region of the ToMV genome. This plasmid, pSLN, was used to inoculate several host plants of ToMV. Among five plant species tested, only Chenopodium quinoa accumulated large amounts of viral particles. The infectivities and systemic movements of the resulting viruses were the same as those of virus preparations obtained from a ToMV infection of C. quinoa. Primer extension analyses revealed that the 5' end of the viral genomic RNA was identical to those of RNAs isolated from virus progeny of an infection with T7 transcripts analogous to pSLN. Moreover, the insertion in the 5' untranslated region of the viral genome was stably maintained through several systemic passages of the virus. Thus, inoculation of plants with a plasmid containing a cDNA clone of an RNA virus under the control of a eukaryotic promoter seems to be a convenient alternative to the generation of in vitro transcripts and should facilitate the analysis of viral mutants generated at the DNA level.

Base Sequence

[In vitro proliferation of human bone marrow cells--inhibition by components of Candida albicans].

Candida albicans (CA) components influence the proliferation of human bone marrow cells in vitro (colony-forming assay). Number of colonies per 10(5) bone marrow cells after cultivation with rHuGM-CSF (maximal plateau colony formation): 46.2 +/- 9.1 (n = 6); after cultivation with rHuGM-CSF in combination with CA proteins: 0.05 mg protein/ml: 33.4 +/- 4.6 (n = 3); 0.10 mg protein/ml: 20.8 +/- 3.6 (n = 3).

Bone Marrow Cells

Implant and prosthetic treatment of the edentulous maxilla using a bar-supported prosthesis.

Functional and anatomical considerations led to a new concept of an implant-supported bar prosthesis in the edentulous maxilla. The cantilever situation is avoided by the placement of endosseous cylindrical implants (type IMZ) in the maxillary tuberosities distal to the maxillary sinus. Full arch support is provided by the symmetrical insertion of six IMZ implants in the tuberosity, canine, and incisor regions. After 4 months of healing, a milled precision bar and removable prosthesis are fabricated and supported by the implants.

Aged

Influence of leukemia P388 on plasma concentration-time profiles of bendamustine in B6D2F1 mice.

It was the aim of this study to investigate whether leukemia P388 being an important murine transplantation tumor may alter the plasma concentration-time profiles of the alkylating antineoplastic agent bendamustine (1) in mice. In an advanced tumor stage the rapid decline of 1 plasma levels was found to be retarded in tumor-bearing in comparison to tumor-free animals both after i.v. and p.o. drug administration. These changes cannot be explained by the neoplasia-related depression of drug metabolism whereas the 1-containing ascitic fluid may be a possible reason for the prolonged drug levels in plasma. After p.o. administration of 1, the bioavailability of the drug was found to be increased in the leukemia-bearing animals.

Administration, Oral

[The mobile rheumatoid health unit--an ambulatory consultation from the viewpoint of the physician and patient].

The acceptance of a university-based outpatient department (Department of Rheumatology, Hannover Medical School, FRG) has been investigated. Ninety-five former patients with RA, previously treated in the department were interviewed by phone. 312 general practitioners from the city of Hannover received a mailed questionnaire. Patients were asked why they had left outpatient department care; questions for general practitioners dealt with types of referral. Despite high satisfaction with the outpatient unit in both groups, we found several shortcomings which possibly might influence discontinuation of treatment and non-utilization of the department: patients and physicians criticized the scheduling system and waiting times. Both groups complained of frequently changing doctors. The general practitioners wanted more contact with the department and more information about the unit. A small group of patients and referring physicians expressed resignation.

Ambulatory Care Facilities

Factors determining the frequency of plasmid cointegrate formation mediated by insertion sequence IS3 from Escherichia coli.

Transposition events mediated by plasmidborne copies of the insertion sequence IS3 of Escherichia coli are difficult to detect because of a low frequency of cointegrate formation. We found that cointegration activity could be strongly enhanced by using plasmid constructions in which a second IS3 element, disabled by a large deletion, was placed adjacent to an intact IS3 copy. Attempts to construct plasmids containing two adjacent intact IS3 copies were unsuccessful, probably because of instability. Transpositional hyperactivity of tandemly duplicated IS sequences was previously described for spontaneous duplications of IS21 and IS30 and may well be a more general phenomenon. The frequency of cointegration events was also strongly increased in an E. coli strain deficient in Dam methylation, suggesting that IS3, like some other Dam site-containing IS elements, is regulated by the Dam methylation system. Insertion sites were strongly clustered within the target lambda repressor gene: however no sequence specificity determinants could be identified. All insertions analyzed carried the IS element in the same orientation; target sequence duplications were mostly 3 bp, but in some cases 4 bp long. To obtain information about the roles of the open reading frames (ORFs) in IS3, we constructed plasmid-borne mutant elements in which potentially functional reading frames were inactivated by site-directed mutations; the mutants were introduced into partial tandem constructions and tested in cointegration assays. Mutations inactivating the putative initiation condons of ORF I and II in the intact element reduced insertion activity to less than 4% of the wild type, whereas the introduction of a termination codon into ORF IV had no effect on cointegration frequency.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence