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Biomedical subjects

E Schäffer

Publications and source records attributed to E Schäffer.

At least 19 recordsLinked to original sources

Capillary instabilities by fluctuation induced forces.

The spontaneous break-up of thin films is commonly attributed to the destabilizing effect of van der Waals forces. Dispersion forces can be considered in terms of the confinement of the electromagnetic fluctuation spectrum. The principle of confinement is more general than the usual argument of interacting dipole fluctuations. It includes also disjoining pressures that are caused by thermal fluctuations. In this context, we review recent publications on the dewetting of thin polymer films, and argue that the presence of an acoustic disjoining pressure is necessary to adequately describe some of these experimental results.

Journal Article↗

Dynamic domain formation in membranes: thickness-modulation-induced phase separation.

A simple model investigates the amplification of fluctuations on membranes constituted of two lipids having different lengths. Van der Waals and electrostatic interactions across the lipid bilayer result in a destabilization favoring thickness variations of the membrane. Close to spontaneous demixing of the two components, the additional gain in free energy due to thickness undulations shifts the stability boundary which promotes phase separation into domains. Interestingly, this effect can be induced by an applied electric field or membrane potential. In biological systems, the dynamic model presented here indicates that electric fields might be important for controlling phase separation and the formation of domains called "rafts".

Cell Membrane↗

Acoustic instabilities in thin polymer films.

The spatial confinement of a fluctuation spectrum leads to forces at the confining boundaries. While electromagnetic (EM) fluctuations lead to the well-known dispersion forces, the acoustic analogy has widely been neglected. We show that the strength of the forces resulting from confined acoustic modes may be of the same order of magnitude as van der Waals forces. Additionally, the predicted scaling behavior is identical to the non-retarded case of the EM fluctuations. Our results suggest that dewetting experiments using polymer films are strongly influenced by the acoustic dispersion forces.

Journal Article↗

Effect of oral ZnDTPA on late effects of injected plutonium in rat.

PURPOSE: To reduce the long-term toxicity of 239Pu in rats by lifetime drinking of ZnDTPA solution and to investigate possible side-effects of the drug. MATERIALS AND METHODS: Male Sprague-Dawley rats received a single injection of 239Pu citrate, alone or plus oral ZnDTPA. Additional groups were administered only ZnDTPA. Late tissue changes were evaluated by post-mortem examination, X-rays and histologically. RESULTS: The incidence of rat bearing osteosarcoma decreased after treatment to 35% as compared with 53% in untreated controls. The proportional incidence of osteosarcomas was reduced after ZnDTPA by more than the corresponding removal of 239Pu. Unexpectedly in the male rat, mammary tumours, mostly malignant, developed in 20% of rats that received 239Pu as compared with 0.5% in the untreated controls. After a lifetime drinking solely 3 x 10(-3) M ZnDTPA the incidence of diffuse glomerulosclerosis reached 29% as compared with 10% in controls. CONCLUSIONS: In rat, protracted oral administration of ZnDTPA reduced the incidence of osteosarcomas after injection of 239Pu, even if treatment started with a delay of 1 month. In the latter case, however, more soft tissue damage was found than after treatment beginning at 4 days post-239Pu. An increased incidence of diffuse glomerulosclerosis was observed as a side effect of oral ZnDTPA only when given continuously, alone and in high amounts.

Administration, Oral↗

Dosimetry and pathology of 237Np in female rats.

Female Sprague-Dawley rats, 10-12-week old and weighing about 240 g, were injected intravenously with 237Np-nitrate. In the toxicological study 77 rats served as controls and 28 rats per group received single doses of 5.2 and 26 kBq, respectively, per kg body weight. In addition, 12 rats of each injection level, sacrificed at defined points in time, were used for dosimetric studies. During the whole life-span the body weight and 237Np whole body-content of each animal were recorded. After death a detailed pathological examination was made of each animal in the cronical study. One day after injection 48% of the injected activity was in the skeleton, 9.3% in the liver, 3% in the kidneys and 4.4% in the rest of the organs. Whereas in all organs the activity decreased very fast, the half-life in the skeleton was about 1400 days. The bodyweights were comparable in the three groups, but the life span decreased from 800 days (control group) to 644 days after injection (26 kBq kg-1 body weight group). The main lesions in the female rats were mammary tumors (73%) and pituitary gland tumors (52%). With increasing activity the incidence of pituary gland tumors decreased and that of osteosarcomas increased from 1.3% (control group) to 32% (26 kBq kg-1 body weight group), whereas the remaining lesions showed no influence on the activity.

Animals↗

[Pholedrine for determining the site of Horner syndrome].

BACKGROUND: Pharmacologic testing by indirect acting sympathomimetics like hydroxyamphetamine may determine the site of the lesion in Horner's syndrome. Pholedrine is chemically similar to hydroxyamphetamine. Therefore we examined if it shows the same effects in normal subjects and in patients with Horner's syndrome. METHODS: Pupil diameter was measured by means of standardized photography before and after single and with different intervals repeated administration of pholedrine eye drops in normal subjects. In 18 patients with Horner's syndrome and known hydroxyamphetamine test results, a pholedrine test was carried out analogous to the hydroxyamphetamine test. RESULTS: Pholedrine dilates the normal pupil by 2.2 mm (mean). It acts at the longest 8-10 hours with maximal effect between 20 and 90 minutes. After this period its effect decreases rapidly. It acts independently from age and from baseline pupil diameter. Given repeatedly the second administration reaches the same mydriatic effect as the first only if the interval between both applications is 72 hours or more. This is because it needs some time to refill the noradrenaline stores in the sympathetic neuron innervating the dilator muscle of the pupil. In Horner's syndrome pholedrine dilates the involved pupil only minimally in case of a postganglionic lesion, and in case of a preganglionic lesion it dilates the pupil even slightly more than the normal fellow pupil. It shows the same effect as hydroxyamphetamine. There are only few side effects. CONCLUSION: Pholedrine is a substitute for hydroxyamphetamine to localize the site of the lesion in patients with Horner's syndrome.

Adolescent↗

Histological and biochemical characterization of the murine cataract mutant Nop.

Nop, a spontaneous murine dominant cataract mutation, was detected by slit lamp investigations and preliminary characterized as a nuclear opacity. Histological investigations confirmed these findings and revealed additionally polar cataracts with vacuolization. In contrast to wild-type lenses, the nuclei of the cortical cells could also be detected in the area of the lens nucleus in Nop lenses. No other pathological alterations were found in the eyes. Lens wet and dry weights, as well as the content of water-soluble lens proteins, were reduced in heterozygous and homozygous mutants. The body weight was only slightly altered, indicating a rather lens-specific growth retardation. Some parameters concerning the osmotic state of the lens were changed, however, only in the homozygous mutants. Electrophoresis of the water-soluble lens proteins of the mutants revealed either additional bands, not present in the wild types, or bands of overrepresented proteins only slightly present in wild-type lenses. The changes might be related to the reduced amount of gamma-crystallins, which alters the composition of lenticular proteins in the mutants. Northern blots probed with cDNA specific for alpha-, beta- or gamma-crystallin genes suggested a reduced transcription of the gamma-crystallin genes. In contrast, the transcription of alpha- and beta-crystallins appeared to be similar in wild type and the mutants. The selective reduced amount of gamma-crystallin specific RNA can be discussed as a biochemical indicator for the histologically observed changes of differentiation in the cataractous Nop lenses.

Animals↗

Dose rate and fractionation of total body irradiation in dogs: short and long term effects.

Variations of regimens of total body irradiation (TBI) were investigated in the dog as a preclinical model for bone marrow transplantation. Inactivation of hemopoietic precursor cells (CFU-GM) was studied following irradiation of marrow in vitro, following TBI at sublethal doses in vivo and following autologous transplantation of marrow obtained after sublethal TBI. Inactivation and recovery of CFU-GM as well as restoration of hemopoiesis following autologous transplantation was independent of the dose rate, but nadirs of blood counts were lower following sublethal TBI with the higher dose rate. Acute non-hemopoietic toxicity of TBI depended on the dose, the dose rate and the total treatment time and not on the fractionation regimen. At a total dose of 25 Gy acute mortality was prevented by prophylactic administration of oral, non-absorbable antibiotics. Late mortality was due to degenerative and autoimmune-like disorders with or without infections and to malignant tumors. Evaluation of long-term survival is still preliminary, since surviving dogs of two groups (10 Gy as single dose, 25 Gy as hyperfractionated TBI) have not yet reached the median survival time of their group. So far, long-term survival depended on the total dose (p = 0.05) and, possibly, the fractionation regimen (p = 0.12). The latency period until development of malignant tumors was influenced by the total doses given in the same treatment time (p = 0.05) and by the total treatment time for equal doses (p = 0.04). It was concluded that TBI at a low dose rate may give the best therapeutic ratio of inactivation of hemopoietic precursor cells to acute toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Characterization of Cat-2t, a radiation-induced dominant cataract mutation in mice.

A dominant cataract mutation was detected recently among the offspring of x-ray-irradiated male mice. The mutation, which causes total lens opacity, has provisionally been designated by the gene symbol Cat-2t. In the lenses of heterozygous and homozygous Cat-2t mutants, the epithelial and fiber cells were swollen and the lens capsule was ruptured. The histologic analysis demonstrated a complete destruction of the cellular organization of the lens, which might be caused by its altered developmental processes. The data derived from biochemical investigations indicate that biochemistry of the cataractous Cat-2t lenses is affected: the osmotic state as indicated by the increased water content and increased Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity; the energy state as indicated by the decreased adenosine triphosphate (ATP) concentration; and the redox state as indicated by the enhanced content of oxidized glutathione. Additionally, the lenticular protein composition is altered because of the presence of vimentin in the water-soluble fraction. This cannot be explained by the enhanced crosslinking activity of transglutaminase. The changes of the osmotic, energy, and redox states are considered to be secondary in relation to the altered lenticular development. In contrast, the variations concerning vimentin and transglutaminase might be a biochemical indication of the changed development. Possible similarities to other dominantly expressed murine cataract mutants are discussed.

Adenosine Triphosphate↗

Characterization of Scat (suture cataract), a dominant cataract mutation in mice.

The autosomal, dominant mutation Scat (suture-cataract) was found in (101/El x C3H/El)F1-hybrid mice. The severity of the cataract is dependent on the gene dose. The mutation causes an anterior suture opacity in heterozygotes amd microphthalmia with vacuolated lenses in homozygotes. In histological sections of lenses the heterozygotes exhibit a hydropic swelling of lens epithelium, whereas in homozygotes interruption and degeneration of lens fibers as well as clefts and folds of the capsule were observed. The mutation has a complete penetrance and constant expressivity. The body weight of the mutants is not altered; the mutation has no effects on fertility or viability. The lens wet and dry weights are diminished (more pronounced in the homozygotes). The water content of the lens is enhanced only in the homozygous Scat mutants. Biochemically, the lenticular content of water-soluble proteins is decreased in the homozygous Scat mutants. By electrophoresis, in the lenses of homozygous Scat mutants a different pattern of water-soluble proteins could be observed. The lenses of both, heterozygous and homozygous Scat mutants exhibit enhanced Na+,K+-ATPase activity and a decreased ATP concentration. The genetical, morphological or biochemical data suggest that the effect of the Scat mutation is distinct from other described cataract mutations in mice.

Animals↗

[Multiple ocular coloboma (MOC) with persistent pupillary membrane in the snow leopard (Panthera uncia)].

In a litter of three snow leopards, bilateral colobomata of the upper temporal eyelids, bilateral persistent pupillary membranes and a unilateral coloboma of the optic nerve entrance are described as "Multiple Ocular Colobomata" (MOC). The causal pathogenesis of each of the colobomata is discussed comparatively. The colobomata of the eyelids, essential feature of the MOC syndrome in snow leopards, are most probably not of hereditary, but rather of intrauterine infectious viral origin.

Animals↗

Incidence, morphology, and ultrastructure of spontaneous thymoma--the most common neoplasm in W/Nhg rats.

Spontaneous thymoma was observed with an incidence of 97 and 36% in female and male rats, respectively, from an inbred Wistar/Neuherberg strain (W/Nhg). The thymomas often caused dyspnea and were occasionally the direct cause of death. The neoplasms resembled human thymomas and showed a variable cell composition, ranging from mainly lymphocytic to mainly epithelial. The detailed ultrastructural findings are described and compared with those in other rat thymomas and in human thymomas. A characteristic feature of all dividing lymphocytes was the presence of often multilayered, confronting cisternae. As in more than 50% of human thymomas, W/Nhg rat thymomas were not associated with myopathies or any other possibly autoimmune diseases. They may thus offer a useful model for the study of thymoma without associated parathymic syndromes.

Age Factors↗

Short-term studies with the cryptating agent hexaoxa-diaza-bicyclo-hexacosane in rats.

In short-term experiments rats received single doses of 50, 100, and 500 mumoles/kg of the cryptating agent A 222. A dose-related increase in the activities of GOT and GPT in the serum was observed 6 h after treatment, reaching values up to eleven and three times that of the controls, respectively. However, the enzyme activities returned to the control levels within 3 days. The activity of alkaline phosphatase and the levels of protein and cholesterol in serum were not altered during the observation period of 7 days. Histopathological examinations did not show any changes in the liver, kidney, heart, lung, thymus, spleen, or intestine. The elevations of GOT and GPT seem to be due to a transient liver lesion, since no histopathological alterations of the liver became apparent. These results show, that after single applications of A 222 at all doses used, no severe lesions occur in the observed organs.

Alanine Transaminase↗

Fractionated total body irradiation and autologous bone marrow transplantation in dogs: hemopoietic recovery after various marrow cell doses.

Hemopoietic recovery was studied in dogs given 2400 R fractionated total body irradiation within one week and graded doses of cryopreserved autologous bone marrow. Complete hemopoietic recovery including histology was observed after this dose and sufficient doses of marrow cells. Doses of more than 5.5 X 10(7) mononuclear marrow cells/kg body weight were sufficient for complete recovery in all dogs, 1.5 to 5.5 X 10(7) cells/kg were effective in some of the dogs and less than 1.5 X 10(7) cells/kg were insufficient for complete recovery. Similarly, more than 30,000 CFUc/kg body weight were required for hemopoietic recovery. The optimal marrow cells dose which has been defined as the minimal dose required for the earliest possible recovery of leukocyte and platelet counts was 7-8 X 10(7) mononuclear marrow cells/kg body weight. It has been concluded that fractionated total body irradiation with 2400 R does not require greater doses of marrow cells for hemopoietic reconstitution than lower single doses and that the hemopoietic microenvironment is not persistently disturbed after this dose.

Animals↗