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Biomedical subjects

R Schmidt

Publications and source records attributed to R Schmidt.

At least 469 records · Page 26Linked to original sources

Short-term effects of oral enoximone on hemodynamics, exercise capacity, anaerobic threshold, and arrhythmias in congestive heart failure.

Enoximone, a phosphodiesterase-inhibitor, is a potent inotropic vasodilator agent that causes a marked improvement in hemodynamics in patients with congestive heart failure. The acute effects of oral enoximone on rest and exercise hemodynamics, ejection fraction, aerobic metabolism, exercise capacity, and arrhythmias were studied in 11 patients with moderate to moderately severe dilative cardiomyopathy after 8 days of enoximone (100 mg tid) in addition to baseline therapy (diuretics and digitalis). The cardiac index increased from 2.44 +/- 0.45 to 2.72 +/- 0.50 l/min/m2 (p less than 0.01) at rest and from 4.00 +/- 0.96 to 4.75 +/- 0.95 l/min/m2 (p less than 0.005) during exercise. Pulmonary wedge pressure decreased from 16.8 +/- 7.3 to 12.5 +/- 6.5 mmHg (p less than 0.005) at rest and from 28.2 +/- 8.0 to 24.5 +/- 10.3 mmHg (p less than 0.05) during exercise. Systemic vascular resistance decreased from 1608 +/- 243 to 1495 +/- 300 dynes*sec*cm-5 (p less than 0.05) at rest and from 1152 +/- 155 to 1027 +/- 236 dynes*sec*cm-5 (ns) during exercise. The anaerobic threshold, which was recorded simultaneously, increased from 13.2 +/- 2.7 to 15.5 +/- 2.5 ml/kg/min VO2 (p less than 0.02). The radionuclide ventriculography ejection fraction improved from 21.7 +/- 5.0 to 28.1 +/- 9.1% (p less than 0.01) during exercise; the changes at rest were not significant (20.8 +/- 6.2 vs 25.8 +/- 8.4%). Exercise tolerance showed an increase of 16% (492 +/- 133 to 573 +/- 135 sec, p less than 0.005). The resting heart rate remained unchanged (81.8 +/- 13.4 vs 81.8 +/- 11.9). Interestingly, 24-h Holter monitoring revealed more or new repetitive arrhythmias in 9/11 patients.

Adult↗

Magnetic resonance imaging white matter lesions and cognitive impairment in hypertensive individuals.

To search for a morphologic basis of cognitive impairment possibly associated with essential hypertension, we studied 35 otherwise asymptomatic hypertensive individuals (mean age, 38.7 years; range, 22 to 49 years) and 20 normotensive control subjects (mean age, 37.9 years; range, 26 to 49 years) using neuropsychologic tests and magnetic resonance imaging. Irrespective of drug treatment, hypertensive individuals performed significantly worse than did control subjects when assessed for verbal memory and total learning and memory capacity, while there were no differences in test results of visual memory, attention, vigilance, and reaction time. The hypertensive individuals also described themselves as less active but ranked similar on five other mood subscales. Punctate high-signal intensities of the white matter were found almost twice as often in the hypertensive group (38%) as in the control group (20%). There was no difference in test performance between hypertensive individuals with and those without white matter lesions, however. Our results confirm the presence of subtle neuropsychologic deficits and indicate a higher frequency of white matter signal abnormalities in essential hypertension, as shown on magnetic resonance imaging, but do not indicate a correlation of these findings with each other.

Adult↗

Ependymin as a substrate for outgrowth of axons from cultured explants of goldfish retina.

Ependymin, a prominent protein of the brain's extracellular fluid (ECF) was previously implicated in the consolidation of memory and in the activity-driven sharpening of the retinotectal projection. Because both these phenomena probably involve the growth and elaboration of appropriate synapses, we have tested whether ependymin can serve as a substrate for the growth of axons from goldfish retinal ganglion cells in a culture assay. Ependymin (Ep), laminin (LAM), polylysine (PL), and Concanavalin A (Con A) were plated on glass coverslips either uniformly or in striped patterns. Ep alone, either soluble or partly polymerized (by dropping calcium concentration and pH), was a good substrate for axonal outgrowth, as good or better than PL and Con A, but not as good as LAM. Neurites grew faster on LAM (71 microns/h) than on Ep (32 microns/h) or on PL (22 microns/h). Fasciculation was low on LAM, intermediate on Ep, and highest on PL. In exclusive side-by-side stripe assays, axons preferred LAM over Ep, but gave weak or no preference for Ep over Con A or PL. With stripes of LAM + Ep alongside pure LAM, the axons preferred the mixture of LAM + Ep. When antibodies to Ep were plated in stripes over continuous Ep substrate, the axons avoided the antibody-blocked stripes and grew on the Ep stripes. Antibodies to Ep did not, however, block growth on laminin substrates, nor did antibodies to LAM block growth on Ep. Dot blots and western blots showed very little cross recognition between the antibodies. Ependymin is a good substrate for neurite outgrowth, which is normally present in ECF, and adhesion to Ep is independent of LAM and possibly additive to it.

Animals↗

MRI in tuberculous meningoencephalitis: report of four cases and review of the neuroimaging literature.

The contribution of MRI is reported in four adult patients with tuberculous meningoencephalitis (TbM) and with autopsy correlation in one. Contrast-enhanced T1-weighted MRI revealed the characteristic basal meningeal inflammation of TbM and its focal spreading into adjacent brain. Mixed and T2-weighted pulse sequences delineated a plethora of parenchymal abnormalities. Their relation to TbM was established by a close matching of the patient's neurological findings, contrast enhancement or a change in lesion size. The latter accurately reflected the clinical course in all patients. It remained difficult, however, to distinguish between ischaemic and inflammatory changes, which in some locations were intermixed even histologically. From our experience and that of other groups, MRI provides more diagnostic information in TbM than CT. Moreover, MRI promises to be a useful tool for monitoring treatment response.

Adolescent↗

The pharmaceutical physician--requirements for the position.

Physicians looking for a position as pharmaceutical physician are usually uncertain whether they are suitable for this activity by training and personal abilities. The main requirements are a major interest in therapeutics and research as well as the ability to treat a disease as an entity instead of the individual patient. The pharmaceutical physician is a specialist in the area of drug development. Even by treating populations and diseases his ultimate goal is to contribute to better care for the individual patient. Requirements for training and the personal abilities necessary for the position of a pharmaceutical physician are described and recommendations given for applicants.

Drug Industry↗

Biological assays for irritant, tumor-initiating and -promoting activities. III. Computer-assisted management and validation of biodata generated by standardized initiation/promotion protocols in skin of mice.

The initiation/promotion standard protocol 28 (protocol 28), developed and used previously as an experimental model to verify the cancerogenic process of initiation/promotion in mouse skin, was revised in three aspects: (a) statistically it was shown sufficient to use, per promoter dose group, 16 colony-outbred female NMRI mice: (b) by weekly individual records of tumor response (and health status) of each mouse in a dose group, cumulative tumor incidences (and mean and extreme body weights) are determined; from these data the collective records (tumor response, health status), the only data accessible from protocol 28, may be generated in addition; (c) the details of dose groups and all data on tumor response and health status are processed by computer using the program package PAPILLOM. The latter was developed specifically for this purpose, is written in the programming language APL and designed for easy handling by staff of animal laboratories. The program package calculates, from the individual records per promoter dose group, cumulative tumor incidences (and survival data) with confidence limits for any one exposure time, and the package may be linked to programs for statistical validations. In addition, from the collective records it calculates the tumor rates, tumor yields and survival rates for any one exposure time. These data, obtained by either of the standard protocols (16 or 28), are fully comparable. For pure compounds they may be used to calculate semiquantitative tumor-promoting potencies. These values for more than 80 polyfunctional diterpenes of the tigliane, ingenane and daphnane type, scattered in or calculated from previous papers, together with their irritancies, were compiled. Within recent years, computer-assisted standard protocol 16 has been used to handle and evaluate about 1000 promoter dose groups. Protocol 16 allows one to extract and utilize more and better toxicological information on tumor response and health status from any one dose group, utilizing significantly fewer experimental animals than required by protocol 28. Thus, the computer-assisted standard protocol 16 optimizes the utility of the experimental model of mouse skin for the amount, quality and management of experimental data as well as for the requirements of animal protection.

Animals↗

[Integrated and frequency spectra of the electromyograms in patients with temporomandibular symptoms].

With the aid of bipolar surface electrodes, the electromyographic activity of the anterior temporal and the superficial masseter muscles were recorded bilaterally and evaluated by counting the integrated potentials and mean power frequency using Fourier's analysis. A comparison between 17 patients with myofacial pain dysfunction (average age 21.3 years) and a group of 20 controls (average age 20.5 years) revealed a significantly greater activity in patients with pain syndrome, while no significant inter-group difference in mean power frequency was seen. The differences in the level of activity between the right and left sides in the control group were significantly smaller than in patients with pain dysfunction. An investigation of measures aimed at reducing the right/left asymmetry in a further 14 patients with pain dysfunction revealed the practice of "maximum occlusion with feedback" to be the most effective measure.

Adolescent↗

Determination of retinoid activity by an enzyme-linked immunosorbent assay.

In normal human keratinocytes, retinoic acid suppresses the expression of the plasma membrane associated enzyme transglutaminase (TGm) at the pretranslational level. This finding led us to develop an enzyme-linked immunosorbent assay (ELISA) for the evaluation of the biological activity of retinoids, i.e., natural and synthetic derivatives of vitamin A. In this assay, keratinocytes are cultured in a 96-well cluster in the presence of different retinoid concentrations. The expression of TGm is then quantified, without any extraction or purification step, using a TGm-specific monoclonal antibody and a peroxidase-conjugated secondary antibody. The dose-response curves obtained show this ELISA to be a sensitive and reproducible assay to determine the potency of retinoids.

Animals↗

Hepatic uptake of fluorescein, investigated by video fluorescence microscopy and digital image analysis.

We evaluated fluorescence microscopy combined with digitized image analysis for the investigation of fluorescein transport in the intact rat liver. The images of the surface of isolated rat livers which were perfused directly under a microscope were projected onto a silicone-intensified target camera, stored on a video tape and analyzed with a microcomputer equipped with an image digitizer. It was shown that, after correction of the day-to-day variability of the optical and electronical system, the increase in fluorescence intensity of the liver surface following fluorescein infusion depended linearly on the fluorescein concentration in the perfusion medium up to 1 mM. Since, under the conditions used, biliary secretion and metabolic influences were found to be insignificant the uptake mechanism is probably predominantly simple diffusion.

Animals↗

Potential photosensitizers for photodynamic therapy. III. Photophysical properties of a lipophilic chlorin and its zinc and tin chelates.

Photophysical properties of a lipophilic chlorin derivative and its zinc and tin chelates were investigated in chloroform. The quantum yields of the fluorescence phi F, of the S1----T1 intersystem crossing phi T and of singlet oxygen (1 delta g) formation phi delta, as well as the Stern-Volmer constants for the quenching of the S1 states by oxygen and the rate constants of quenching of O2(1 delta g) by the chlorins were measured. In comparison to the metal-free chlorin an increase of phi T and a decrease of phi F have been observed for the metal-containing derivatives, whereas the phi delta values remain constant.

Chelating Agents↗

Identification and map position of YAC clones comprising one-third of the Arabidopsis genome.

YAC clones corresponding to 125 Arabidopsis thaliana RFLP markers have been identified. At least one YAC clone has been isolated for each of the RFLP markers tested. Based on CHEF gel analysis of 196 clones, the mean insert size of the available Arabidopsis YAC libraries is approximately 160 kb. The YACs of known genetic map location encompass about 30% of the Arabidopsis genome. The results presented here represent a first step towards assembly of an overlapping YAC library of the A. thaliana genome.

Arabidopsis↗

[Conventional and cine-MRT in patients with aneurysms of the abdominal aorta].

We studied 40 patients with aneurysms of the abdominal aorta by MRI. These results were compared with those obtained by real-time sonography (n = 40), angiography (n = 32) and CT (n = 16). In 30 patients the imaging results were compared--as far as possible--with the operative findings. MRI proved more reliable, especially if compared with sonography, in evaluating renal or iliac artery involvement. Mural thrombi were detected more often (93%) by MRI than by CT (85%) or sonography (83%). Cine-MRI showed strong turbulences in 33%. Turbulences did not correlate with the size of the aneurysm.

Adult↗

Mycoplasma phocarhinis sp. nov. and Mycoplasma phocacerebrale sp. nov., two new species from harbor seals (Phoca vitulina L.).

A total of 120 mycoplasma strains were recovered from 97 of 265 diseased seals investigated during the seal epidemic in the North Sea and in the Baltic Sea in 1988. Mycoplasmas were isolated from the respiratory tracts (including lungs), hearts, brains, and eyes of the seals. Thirty strains were filter cloned and investigated for their morphological, biochemical, and serological characteristics compared with the characteristics of previously described species. The results of an indirect immunofluorescence test, a growth inhibition test, and an immunobinding assay showed that these strains belong to two new species, for which the names Mycoplasma phocarhinis and Mycoplasma phocacerebrale are proposed. M. phocarhinis (17 strains) did not ferment glucose or hydrolyze arginine but did reduce tetrazolium chloride and potassium tellurite and produced films and spots. M. phocacerebrale (13 strains) metabolized arginine but not glucose and produced phosphatase but did not reduce tetrazolium chloride and potassium tellurite. Both species lysed sheep erythrocytes but did not absorb sheep or guinea pig erythrocytes. The type strain of M. phocarhinis is strain 852 (= ATCC 49639), and the type strain of M. phocacerebrale is strain 1049 (= ATCC 49640).

Animals↗

Forespore-specific transcription of a gene in the signal transduction pathway that governs Pro-sigma K processing in Bacillus subtilis.

We present studies on the regulation of a developmental gene (spoIVB) whose product is required at a late stage of morphogenesis during the process of sporulation in Bacillus subtilis. Earlier work implicated the spoIVB gene product in a signal-transduction pathway that governs the conversion of pro-sigma K to the mature and active form of the mother cell sigma factor, sigma K, in response to a signal generated within the forespore chamber of the sporangium. We now show that (1) spoIVB is induced at the engulfment stage of sporulation, (2) this transcription is restricted to the forespore, and (3) spoIVB is under the direct control of the forespore sigma factor sigma G. The discovery that spoIVB is a forespore-expressed gene suggests that the spoIVB gene product, or a developmental event under its control, triggers the processing of pro-sigma K and thereby mediates the coupling of sigma K-directed gene expression in the mother cell to sigma G-directed gene expression in the forespore. We also show that spoIVB transcription is partially dependent on the action of the mother cell regulatory gene spoIIID, a finding that suggests that the transcription of certain forespore-expressed genes is influenced by events in the mother cell.

Bacillus subtilis↗

Modulation of cellular cholesterol and its effect on cornified envelope formation in cultured human epidermal keratinocytes.

When cultured human epidermal keratinocytes (NHK) reach confluence they start to differentiate and an increase in the total cellular cholesterol content is observed. This increase parallels the appearance of a characteristic feature of terminal keratinocyte differentiation, the spontaneous formation of cornified envelopes (CE). Synthesis of CE is catalyzed by the plasma membrane-associated transglutaminase (TGm). Supplementation of the medium with inhibitors of cholesterologenesis suppressed increase in cholesterol levels and CE formation but did not interfere with TGm expression or TGm activity. Modulation of the plasma membrane cholesterol-phospholipid ratio of confluent NHK cultures using either pure phospholipid liposomes or liposomes enriched in cholesterol strongly affected spontaneous CE formation. Pure phospholipid liposomes completely inhibited CE formation, whereas cholesterol-enriched liposomes ensured envelope formation, even in the presence of inhibitors of cholesterol synthesis. From these results we conclude that in differentiating NHK an increase in the cellular cholesterol level is part of the differentiation program and is essential for the spontaneous CE formation.

Cell Aggregation↗