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Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 559 records · Page 31Linked to original sources
PubMed1988

Plasma membrane transglutaminase and cytosolic transglutaminase form distinct envelope-like structures in transformed human keratinocytes.

Cross-linked envelope formation in the transformed human keratinocyte line SV-K14 requires treatment of the cells with a Ca2+ ionophore. Depending on the culture conditions, different extracellular Ca2+ concentrations are necessary to trigger the process which is catalyzed by the enzyme transglutaminase. Confluent cells grown in the presence of serum express only the cytosoluble form of the enzyme and need 5 mM Ca2+ for optimum protein cross-linking, whereas serum-starved cells which additionally contain the plasma membrane associated form of the enzyme require only 1 mM Ca2+. The envelope-like structures thus synthesized are morphologically and biochemically distinct.

Cell Line↗
PubMed1988

Inhibition of long-term memory formation by anti-ependymin antisera after active shock-avoidance learning in goldfish.

Ependymins are acidic glycoprotein constituents of goldfish brain cytoplasm and extracellular fluid which are known to participate in biochemical reactions of long-term memory formation. In earlier experiments, anti-ependymin antisera were found to cause amnesia when injected into goldfish brain ventricles after the acquisition of a vestibulomotoric training task. To investigate whether they also inhibit memory consolidation after other learning events the anti-ependymin antisera were injected after an active shock-avoidance learning paradigm, as follows: goldfish were trained in a shuttle-box to cross a barrier in order to avoid electric shocks (unconditioned stimulus) applied shortly after a light signal (conditioned stimulus). Anti-ependymin antisera blocked retention of the learned avoidance when injected 0.5, 4.5 or 24 h after acquisition of the new behavior. They had no effect, however, when injected 72 h after learning. Apparently, long-term memory was already consolidated at this point. Antisera injected 0.5 or 72 h prior to training, also did not influence learning or memory. Thirteen percent of the goldfish fled the light stimulus spontaneously. These fish therefore did not experience the unconditioned stimulus and thus were unable to learn the task. When they were treated with the anti-ependymin antisera and tested 3 days later, the spontaneous escape reaction was not affected (active control group). The ability of anti-ependymin antisera to inhibit memory consolidation and their efficacy after administration at specific time intervals are very similar for the active shock-avoidance learning and for the vestibulomotoric training. We conclude that ependymins are not task-specific, but serve a general function in biochemical reactions essential for long-term memory formation.

Animals↗
PubMed1988

Dose-finding studies in clinical drug development.

A correct dose-finding study is of the utmost importance during clinical development of a new drug. It must define the no-effect dose and the mean effective and maximal effective doses. Then taking tolerability into account, the optimal therapeutic dose range can be selected. To define the dosage schedule the duration of action in man must be tested, if possible together with blood concentration measurements. An adequate dose-finding study shows the optimal doses for double-blind trials in Phase II and large scale trials in Phase III, thereby saving time and effort and reducing the number of patients required. The tendency of clinical experts to try to demonstrate superiority of one drug over another by using doses higher than patients really need must be resisted. The price paid in poor tolerability exceeds any potential benefits.

Clinical Trials as Topic↗
PubMed1988

[Breast reconstruction using a skin expander prostheses following modified radical mastectomy].

In the period from September 1983 to May 1986, 116 breast reconstructions were performed at Heidelberg University Gynecological Clinic with the aid of skin expander prostheses, following modified radical mastectomy (89 primary and 27 secondary reconstructions). In 18% of all cases, complications occurred due to the expanders, the most common being loss of prosthesis material. A total of 82 women have meanwhile had the expander prosthesis replaced by a definitive gel prosthesis in a "second reconstruction phase". Reconstruction of the nipple and areola has been performed in six cases in a third phase. Today, breast reconstruction in one or two stages following modified radical mastectomy represents an integral part of surgical rehabilitation of primarily operable breast cancer in cases, where a primary conservative procedure is out of the question.

Adult↗
PubMed1988

[Rate of local recurrence and survival in patients with breast reconstruction following mastectomy].

A retrospective study was conducted covering 100 patients who underwent breast reconstruction with plastic prostheses following mastectomy during the period from 1975 to May 1986. They were compared with 100 patients (matched pairs) who had not undergone breast reconstruction. No significant difference between the two groups could be found as regards locoregional recurrences or the overall survival rate. The mean observation period was 86.5 months. Surgical removal of local recurrences did not necessarily involve removal of the prosthesis. Therefore, given adequate operability, and experience on the part of the surgeon, a breast reconstruction following mastectomy can now be performed on any patient desiring it to alleviate mental suffering.

Adult↗
PubMed1988

[Amniocentesis following premature rupture of fetal membranes and suspected premature rupture of fetal membranes in late pregnancy].

Amniocentesis during the third pregnancy trimenon in case of suspected premature rupture is performed for two reasons: on the one hand, the maturity parameters can be determined as usual from the amniotic fluid, and on the other hand it serves to determine the presence of germs that may have caused the premature rupture. At the same time, it is possible to confirm the suspicion of premature hydrorrhoea gravidarum by instillation of dyestuff into the amniotic cavity. Premature rupture was confirmed in 21 of 65 cases where clinical findings had not supplied safe evidence; in the remaining 44 cases this method permitted the exclusion of premature hydrorrhoea. An evaluation was performed by means of a retrospective study of parturitions between 1975 and 1985 with regard to late amniocenteses in cases of suspected premature rupture, the investigated parameters being the course of pregnancy and of birth, postpartal state of well-being, bacteriological findings in the amniotic fluid, and results of instillation of blue dyestuff.

Amniocentesis↗
PubMed1988

[Abdominal real-time sonography in patients with vascular prostheses].

100 sonograms were performed in 71 patients up to 13 years (average 21.8 months) after various surgical interventions of the abdominal aorta. Patients were examined e.g. for complications in the early postoperative stage or abnormal local findings and during clinical follow-ups. Ultrasound showed e.g. 13 aneurysms of grafts and anastomoses, 19 haematomas, 4 lymphoceles, 3 graft occlusions and 2 graft infections. Beyond the implantation site in 45 sonograms additional pathological findings were demonstrated, which were unknown in 13 patients (e.g. renal carcinoma, liver metastases, hydronephrosis). In patients with aortic grafts real-time sonography of the abdomen can be regarded as a relatively easily performed, valuable method.

Adult↗
PubMed1988

Spin-labeled phorbol esters and their interactions with cellular membranes. III. Skin irritant and tumor-promoting activities of spin-labeled phorbol-12,13-diesters and relationships to their particular structures.

Sixteen 'doxyl' spin-labeled 12,13-(acetate, acylates) of phorbol were assayed in NMRI mice for irritant and for tumor-promoting activity. The spin-labeled positionally isomeric (n,m)PA- and AP(n,m)-type esters carry straight aliphatic acyl chains of different overall lengths N (number of C atoms). Within the chains the 'doxyl' label is located in different positions (n,m). The potency of some of the esters as irritants and as promoters is comparable to or even higher than that of the prototype diterpene ester promoter 12-O-tetradecanoylphorbol-13-acetate and its positional isomer 12-O-acetylphorbol-13-tetradecanoate. Their irritancies on the ear and their promoting activities on the back skin depend strongly on the structural features of the acyl chain carrying the spin label. Based upon the bioactivities of individual esters biologically meaningful probes were defined for investigations of the molecular interaction of phorbol-ester-type promoters with cellular targets for electron paramagnetic resonance.

Animals↗
PubMed1988

Neuropharmacologic effects of vibration on the dorsal root ganglion. An animal model.

The neuropharmacologic effects of low frequency vibration on the dorsal root ganglion, a reported epidemiological cause of low-back pain, have only recently been described. This investigation was undertaken to validate the hypothesis that substance P and VIP, known to be produced in the dorsal root ganglion cell bodies, will be affected by low frequency vibration. Three New Zealand white rabbits were vibrated at discrete frequencies (2-10 Hz) to determine the resonant frequency of the rabbit spine. The resonating frequency was in the (3.5-5.0 Hz) range. The peak amplitude was at 4.5 Hz. Ten female New Zealand white rabbits were then paired into two groups of five. One group served as a control and had exactly the same procedures performed as the experimental group except for the vibration. The L4-5 and L5-6 dorsal root ganglia were removed bilaterally and prepared for substance P and VIP extraction by radioimmunoassay technique. The control rabbits mean immunoreactive substance P was 14.06 pg/ml tissue, whereas the experimental or vibrated rabbits had a mean of 8.40 pg/ml (P less than 0.003). The control rabbits mean immunoreactive vasoactive intestinal peptide was 9.58 pg/ml whereas the experimental or vibrated rabbits had a mean of 20.9 pg/ml, P less than 0.07. Substance P is only one of several dorsal root ganglion neuropeptides that may play a role in nociceptor transmission. VIP is a neuropeptide that plays a role in reorganization of the nervous system following injury. The effects of low frequency vibration on dorsal root ganglion transmitters are essential to the understanding of vibration as a cause of back pain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Transglutaminases in normal and transformed human keratinocytes in culture.

The transglutaminases of cultured normal and transformed human keratinocytes (line SV-K14) are characterized. Both cell types display two forms of the enzyme, one of which is cytosoluble (TGc) and the other which is associated with the plasma membrane (TGm). Normal keratinocytes contain predominantly TGm, and SV-K14 cells mainly TGc. The ratio of TGm to TGc can be modulated by the culture conditions and correlates with the competence of the cells to form a cornified envelope. TGm and TGc differ in their biochemical and immunological properties. SDS electrophoresis reveals apparent molecular weights of 92 and 85 kD, respectively. Only the activity of TGc is inhibited in the presence of guanosine 5'-triphosphate. Their response to Ca2+ is different: TGc exhibits a sigmoidal activation kinetics with an A50 value of about 200 microM, whereas the kinetics for TGm is hyperbolic with an A50 value of 75 microM. TGm reacts with a monoclonal antibody raised against epidermal "particulate" transglutaminase, and TGc with a polyclonal antibody raised against guinea pig liver transglutaminase. These reactions are very specific and no cross-reaction occurs. The coappearance of TGm with a proteolytic fragment (Mr 82,000) in the cytosol and intracellular particulate fraction of normal human keratinocytes is probably a preparation artifact.

Cell Line, Transformed↗
PubMed1988

Morphological and biochemical characterization of the cornified envelopes from human epidermal keratinocytes of different origin.

The formation of a cornified envelope (CE) is a major event in the terminal differentiation of epidermal cells. Nomarski contrast microscopy of the envelopes purified from different sources reveals the existence of two major, but morphologically distinct classes: the very irregularily shaped fragile type CEf, and the polygonal rigid type CEr. Human keratinocytes in submerged culture are only able to produce type CEf. Specimens from healthy human epidermis contain largely type CEr. Psoriatic scales from different patients show both types in varying proportions. Tape stripping of normal epidermis reveals that type CEf is present in the lowermost layers of the stratum corneum and type CEr is present in the upper layers, indicating that the two types represent a different stage of maturation. Cyanogen bromide peptide mapping of electrophoretically purified envelopes reveals striking differences between cultured keratinocytes, normal epidermis, and psoriatic scales but also slight interindividual variations. This variability supports the view that the molecular CE composition is not strictly determined. On the other hand, no difference could be detected in the peptide maps of CEf and CEr obtained after tape stripping from the same healthy volunteer indicating that CE maturation within the stratum corneum does not involve the provision of qualitatively new proteins.

Cell Differentiation↗
PubMed1988

White matter signal abnormalities in normal individuals: correlation with carotid ultrasonography, cerebral blood flow measurements, and cerebrovascular risk factors.

We studied 52 asymptomatic subjects using magnetic resonance imaging, and we compared age-matched groups (51-70 years old) with and without white matter lesions with respect to carotid ultrasonography, cerebral blood flow (xenon-133 injection), and cerebrovascular risk factors. In the group with white matter signal abnormalities, we noted a higher frequency of extracranial carotid artery disease, a lower mean gray matter blood flow (F1), and a significant reduction (p less than 0.05) in blood flow of the slow-flowing (F2) compartment. Hypertension, diabetes mellitus, and cardiac diseases (p less than 0.002) were found more often in this group. Our results indicate that a higher incidence of changes known to be associated with an increased risk for stroke exists in the presence of white matter lesions in normal elderly individuals.

Adult↗
PubMed1988

Nuclear magnetic resonance image white matter lesions and risk factors for stroke in normal individuals.

The incidence, average number, and localization of lesions of the white matter detected by the T2-weighted nuclear magnetic resonance images among volunteers without cerebrovascular symptoms have been correlated with the number of risk factors for stroke. Accepted risk factors were arterial hypertension, diabetes mellitus, smoking, hypercholesterolemia, and cardiac disease. The 42 subjects examined were divided into Group A (0-1 risk factor, mean age 59.36 +/- 5.73 years), Group B (2 risk factors, mean age 61.54 +/- 8.33 years), and Group C (greater than or equal to 3 risk factors, mean age 62.57 +/- 9.83 years). Multiple risk factors among the age-matched groups was accompanied by a highly significant increase (p less than 0.001, Group A versus Group B; p less than 0.01, Group A versus Group C) of the incidence of white matter lesions. The average number of white matter lesions was increased (p less than 0.001) when Group A was compared with Groups B and C. Ninety-two percent of the white matter lesions were localized in watershed zones. Only 11 of the 155 abnormalities of the white matter detected by nuclear magnetic resonance imaging could be detected by computed tomography. White matter lesions in T2-weighted images appear to be an early stage of cerebrovascular disease.

Brain↗
PubMed1988

Flunarizine vs. propranolol in the prophylaxis of migraine: two double-blind comparative studies in more than 400 patients.

In the course of a 16 weeks' interval treatment of migraine in connection with two multicenter double-blind studies, flunarizine was compared with propranolol in patients suffering predominantly from "classical migraine". Eighty-seven patients from 12 outpatient departments were admitted to the first study, while 434 patients from 99 medical practices participated in the second study. After each month of treatment, the patients were clinically evaluated, and the number, duration, and severity of attacks were documented. Concerning the frequency and intensity of attacks, additional analgesics consumption and overall evaluation, both drugs proved to be highly effective in the practice as well as in the hospital study. The percentage and severity of side-effects were comparable in the two treatment groups. Summarizing, it may be stated that the studies proved the efficacy of flunarizine to be rather similar to that of propranolol in the prophylactic treatment of migraine.

Adult↗
PubMed1988

Flunarizine i.v. in the acute treatment of the migraine attack. A double-blind placebo-controlled study.

Flunarizine, 20 mg by slow intravenous injection, was studied in the acute treatment of migraine attacks in a multicentre, double-blind, placebo-controlled study. At the end of the 60 min observation period, 23 of the 31 (74.2%) patients treated with flunarizine reported complete relief, or a pain reduction of more than 50%, vs. 8 of 29 (27.6%) placebo patients (p less than 0.017). Accompanying symptoms also improved significantly better in the flunarizine than in the placebo group. The investigators evaluated the therapy as good or excellent in 77.4% of the flunarizine and in 27.6% of the placebo patients, respectively. Tolerance of the therapy was good and comparable in the two groups. Somnolence was the only flunarizine-related adverse reaction. Blood pressure and heart rate were not affected. Flunarizine i.v. deserves further study in the acute treatment of a migraine attack.

Adult↗
PubMed1988

Criteria for an increased specificity of MRI interpretation in elderly subjects with suspected multiple sclerosis.

We reviewed the MRIs of 49 asymptomatic volunteers (age range, 31 to 77 years) and of 50 MS patients (age range, 14 to 63) for areas of increased signal (AIS) and features discriminating MS lesions from lesions seen with normal aging. We obtained optimal specificity of MRI interpretation (100%) if we required at least two of the following three AIS features--size greater than or equal to 6 mm, abutting ventricular bodies, infratentorial location--for a positive MRI diagnosis of MS. Applying these criteria to the MRIs of elderly patients with suspected MS should significantly improve specificity (p less than 0.001) over current quantitative criteria (at least three AIS greater than or equal to 3 mm) without significantly decreasing sensitivity.

Adolescent↗
PubMed1988

[Detection of fibria-like surface structures in Staphylococcus saprophyticus as a pathogen in chronic pyelonephritis].

It is reported on a 25-year-old female patient suffering from chronic pyelonephritis. Six times coagulase-negative staphylococci were bacteriological proved in a significant number. Four strains were identified as Staphylococcus saprophyticus. The in each case in the autumn occurring complaints could be correlated well with the seasonal fluctuations of urinary tract infections by S. saprophyticus as described in the literature. Chemotherapeutic measures be determined by the clinical symptoms and subjective complaints of the patient. By an antibiotic therapy only a temporary loss of complaint and normalization of urinary findings, respectively, were obtained. In the presence of a marked leukocyturia a capsula-fashioned variant of S. saprophyticus was established. By scanning electron microscopy investigations fimbria-like surface structures were detected for the first time in this germ species. Three morphological different appendage structures are described. By a hypothetical model possible functions of these structures in the adherence process are discussed.

Adult↗