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Biomedical subjects

G Fischer

Publications and source records attributed to G Fischer.

At least 451 records · Page 25Linked to original sources

Lumbo-peritoneal shunt in non-hydrocephalic patients. A review of 41 cases.

A population of 41 non-hydrocephalic patients in whom a lumbo-peritoneal shunt (LPS) was inserted for various conditions is reviewed. 19 had persistent cerebro-spinal fluid rhinorrhoea following cranial injury, basal skull surgery or of unknown origin, 3 had recalcitrant benign intra-cranial hypertension, 14 had a persistent bulging craniotomy site after operations for intra-cranial tumours or head trauma, 4 had syringomyelia and 1 had a postoperative cervical meningocele. There was no shunt-related mortality. LPS was effective in treating the initial symptomatology in 31 patients. Further revision or removal of LPS were needed on 9 occasions in 8 patients showing shunt-related mechanical or infectious complications or persistent postural headaches. This report demonstrates the safety of the LPS procedure experienced in another population of 146 patients with communicating hydrocephalus operated on in the meantime. According to the authors' experience, the versatility of the clinical applications of LPS seems well established. LPS should be considered when a CSF diversion is required in patients showing absent or minimal ventricular enlargement in the CT scan.

Adult↗

Histochemical and immunohistochemical detection of putative preneoplastic liver foci in women after long-term use of oral contraceptives.

Localized areas with altered enzyme patterns were observed in liver tissue surrounding focal nodular hyperplasia in women after long-term use of oral contraceptives. These localized lesions were of three different types. Type I lesions were characterized by glycogen storage, a reduction in ATPase and an increase in gamma-glutamyltranspeptidase (gamma-GT) and UDP-glucuronyltransferase (UDP-GT) detected immunohistochemically. Type II lesions, which were morphologically very similar to small hyperplastic nodules, showed only a decreased ATPase reaction. Type III lesions showed an increase in gamma-GT (detected histochemically) and a slight reduction in ATPase. The results indicated that in human liver from patients given oral contraceptives long-term, localized lesions with altered enzyme patterns may occur which are very similar to those observed in animal models during experimental hepatic carcinogenesis.

Adenosine Triphosphatases↗

Increased UDP-glucuronyltransferase and gamma-glutamyltranspeptidase in enzyme-altered rat liver lesions produced by low doses of aflatoxin B1.

Preneoplastic liver lesions were produced in female Wistar rats by low doses of aflatoxin B1 (Model 1: administration of 37.5 micrograms/kg 12 and 24 h after partial hepatectomy; Model 2: continuous application of 3.5 micrograms/kg in tap water daily for 28 days with partial hepatectomy after 14 days. The animals then received sodium phenobarbital, 0.1% in tap water, for 180 to 400 days). In both models numerous altered hepatic foci (AHF) and hyperplastic nodules (HN) were detected enzyme histochemically by their negative ATPase and positive gamma-glutamyltranspeptidase reactions. Immunohistochemically these lesions were also UDP-glucuronyltransferase positive. Increased UDP-glucuronyltransferase adds to permanent alterations of a number of drug metabolizing enzymes observed in a variety of different tumor models. These alterations are responsible for the toxin-resistant phenotype (Faber 1984b). Increased gamma-glutamyltranspeptidase was detected both enzyme histochemically and immunohistochemically; whereas gamma-glutamyltranspeptidase activity was present in both AHF/HN and in periportal areas by enzyme histochemistry, the immunohistochemical method selectively stained gamma-glutamyltranspeptidase in AHF and HN. Immunohistochemically detectable UDP-glucuronyltransferase and gamma-glutamyltranspeptidase are markers of putative precancerous liver lesions which may be useful in the analysis of the prestages of liver carcinogenesis.

Aflatoxin B1↗

Analysis of CD3-antibody-mediated inhibition of T-cell activation.

In this study the influence of a non-mitogenic anti-CD3 antibody on accessory cell-dependent antigen and mitogen-induced T-lymphocyte proliferation has been investigated. The antibody was found to completely inhibit PHA, Con A, PWM, and tetanus toxoid stimulation, with no effect on the proliferation induced by the calcium ionophore A23187. VIT3 completely abrogated the production of IL-2 by lectin-stimulated T cells. It had no effect, however, on the IL-2-dependent proliferation of preactivated T-cell blasts. In addition, the antibody was able to elevate free cytoplasmic Ca2+ levels within minutes after the addition to T cells. Detailed time kinetic analyses revealed that the time interval critical for inhibition was significantly dependent on the interaction between T cells and accessory cells. Under standard conditions, in the presence of 10% non-T cells as accessory cells 50% inhibition was still achieved when VIT3 was added to PHA-stimulated T cells as late as 8 hr after the onset of culture. Delayed addition or a decrease in the number of added accessory cells significantly prolonged this time period. Lectin-stimulated T cells can thus obviously be inhibited via CD3 as long as they have not received all signals including those delivered by accessory cells. Although the underlying mechanisms are not clear so far, the observation that VIT3 at the same time triggers an early cytoplasmic Ca2+ response might indicate that it thereby actively interferes with antigen and lectin-initiated activation processes.

Antibodies, Monoclonal↗

Comparison of astrocytic morphology, proliferation, marker profile and response to neurons in wild-type and weaver mutant mouse cerebella in culture.

In serum-free monolayer cultures of early postnatal weaver (wv/wv) cerebellum granule neurons show decreased attachment, survival and neurite outgrowth when compared to wild-type (+/+) littermate cultures. wv/wv Astrocytes display a more epithelioid morphology and altered proliferation. However, both morphology and proliferation of wv/wv astrocytes were reversed to a normal phenotype by addition of purified small neurons from early postnatal cerebella from +/+ animals. Attachment of +/+ neurons to wv/wv astrocytes was not significantly different from that of +/+ astrocytes and antigenic marker profiles of wv/wv and +/+ astrocytes differed only slightly. Attempts failed to revert the abnormal wv/wv phenotype in neurons by addition of gangliosides, triiodothyronine T3, prostaglandin A2, medium containing 1% horse serum, conditioned medium from +/+ cerebellar cultures, or by cocultivation with +/+ astrocytes. We would like to suggest that the primary defect of the wv/wv mutation is predominantly an abnormality in granule cell neurons, but not of the vast majority of astrocytes.

Animals↗

Immunohistochemical differentiation of gamma-glutamyltranspeptidase in focal lesions and in zone I of rat liver after treatment with chemical carcinogens.

gamma-Glutamyltranspeptidase (gamma-GT) is known to be increased in putative pre-neoplastic foci but also in the periportal zone I of rat liver under a variety of circumstances not directly related to carcinogenesis. To be able to distinguish between these two instances gamma-GT was studied by enzyme determination in micro-dissections obtained from the two locations and by both histochemical and immunohistochemical staining in serial sections. Altered hepatic foci and alterations in zone I were produced in three models of hepatocarcinogenesis: initiation by N-nitrosomorpholine and tumor promotion by phenobarbital, continuous administration of 2-acetylaminofluorene and continuous administration of methapyrilene hydrochloride. In micro-dissections gamma-GT activity was similarly increased in focal lesions and in zone I after feeding methapyrilene. Histochemically detectable gamma-GT, stained according to Rutenburg et al. (23), was observed both in zone I and in focal lesions. Focal lesions were also ATPase negative and UDP-glucuronyltransferase positive in all three models. gamma-GT in focal lesions could be selectively detected by immunohistochemical staining using antibodies to the rat kidney enzyme and an indirect peroxidase reaction. These findings suggest immunochemical differences between gamma-GT in focal lesions and in zone I.

2-Acetylaminofluorene↗

[Isolation and characterization of dipeptidylpeptidase IV from human seminal plasma].

Two forms of dipeptidylpeptidase IV with molecular weights (gel distribution chromatography) of 270 kD and about 1450 kD were isolated from human seminal plasma. The enzymes migrating differently in electrophoresis possess identical catalytic properties in regard to pH optimum, kinetic constants and the influence of effectors. The high-molecular form loses at 65 degrees C its enzymatic activity significantly more slowly. After 60 min of incubation at 68 degrees C, human seminal plasma has still about 12-32% (N = 50) dipeptidylpeptidase activity. Through the action of Triton X-100 or chymotrypsin the high-molecular form can be transferred into the low-molecular one without loss of activity. In 80 healthy human sperm donors the average proportion of the low-molecular form of peptidase was determined to be 9-22%.

Chymotrypsin↗

[Determination of dipeptidyl-peptidase IV in biological materials].

Dipeptidyl-peptidase IV (EC 3.4.14.5) can be assayed relatively specifically in crude biological material by determination of the initial rate of formation of 4-nitroaniline from aminoacyl-proline-4-nitroanilides. For clinical purposes tricine buffer, pH 7.4, is employed, because unspecific cleavage of the substrate is minimal under these conditions. Various types of chromogenic and fluorogenic leaving groups can be used to detect the enzyme on solid supports. During the enzymatic hydrolysis of the tripeptides Xaa-Pro-Yaa, there is an increase of absorbance at 228 nm, which is useful for monitoring the enzyme activity. Enzymic activity can also be measured titrimetrically in unbuffered solutions, whereby corrections must be made for the protonation of both substrate and products.

Buffers↗

[Validity of post-proline splitting dipeptidyl aminopeptidase activities in the cerebrospinal fluid for neurologic and psychiatric diagnosis].

The dipeptidyl-peptidase activity of 650 liquores cerebrospinalis was obtained by means of the substrate Gly-Pro-NHNp (Gly-Pro-4-nitroanilid) at pHs of 5.5 and 7.4. In comparison with a reference collective, the suitability of the method as a supplementary liquor parameter in neurological psychiatric diagnosis was examined. The introduction of the measurement at pH 7.4 can be particularly recommended for the distinguishing of bacterial and nonbacterial meningitis.

Dipeptidyl Peptidase 4↗

[The effect of a weak magnetic alternating field on immunobiologic reactions].

UNLABELLED: The influence of a 10 Hz, 0.5 mT (millitesla) alternating magnetic field (rectangular function) on immunologic parameters was investigated. In four chambers, each containing 15 mice, the following electroclimatic conditions existed: conventionally air conditioned laboratory (L), screening of the ambient atmospheric electric fields (F), Faradayscreening plus the above mentioned magnetic field (F + M) and the magnetic field only (M). After 14 days of acclimatizing without magnetic field influence the mice were exposed to the field in the chambers F + M and M for 1, 3, 7 and 21 days, respectively. At the end of the exposure immunological reactions were examined. METHODS: Plaquetest (hemolysis in gel) according to Jerne et al. and determination of the hemagglutination titer. The different groups (L, F, F + M and M) were compared using the Student-t test or variance analysis. RESULTS: After 7 days of field exposure the plaquecount and the hemagglutination titer (converted into the logarithm of base 2) increased significantly in comparison to the controls (L and F, respectively) in some experiments. In experiments carried out with 3 and 21 days of exposure the same tendency (increase of immunological reaction) was detected.

Analysis of Variance↗

Neurite outgrowth patterns in cerebellar microexplant cultures are affected by antibodies to the cell surface glycoprotein L1.

To probe for the role of the L1 cell surface glycoprotein during neurite outgrowth and fasciculation in the early postnatal mouse cerebellar cortex, a microexplant culture system was used. Fasciculation of neurites was reduced in the presence of antigen-binding fragments (Fab) of poly- and monoclonal L1 antibodies, as compared to untreated controls. In addition, speed of neurite outgrowth was enhanced in the presence of antibodies. Migration of cell bodies of small neurons was also significantly increased. Very similar effects on these outgrowth parameters were observed with Fab fragments from poly- and monoclonal neural cell adhesion molecule (N-CAM) antibodies. Antibodies from preimmune sera had no effect. These findings suggest that L1 antigen not only plays a role in adhesion of isolated neural cell bodies and migration of granule cell neurons in the early postnatal mouse cerebellar cortex (Lindner et al., 1983; Rathjen and Schachner, 1984), but also in neurite outgrowth and fasciculation.

Animals↗