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Biomedical subjects

A Anders

Publications and source records attributed to A Anders.

At least 37 records · Page 2Linked to original sources

Melanoma-associated gangliosides in the fish genus Xiphophorus.

Gangliosides from benign and malignant melanomas and from normal skin of the fish genus Xiphophorus were isolated and analyzed by thin-layer chromatography. Individual ganglioside components were characterized by mapping according to their sialic acid content and by cleavage with neuraminidases. In all three tissues examined, sulfatide and the gangliosides NeuAc-GalCer (GM4), II3NeuAc-LacCer (GM3), II3NeuAc-GgOse3Cer (GM2), and II3(NeuAc)2-LacCer (GD3) were found. Ganglioside GD3 yielded a positive reaction, following immunoadsorption with mouse monoclonal antibody R24 on thin-layer plates. Two alkali-labile disialoganglioside species were specifically recognized by mouse monoclonal antibody D1.1, thus indicating the presence of O-acetyl-neuraminic acid residues. One of them, a major ganglioside component of the malignant melanoma, was identified as O-acetyl-GD3, since it could be converted to the R24-positive GD3 ganglioside after alkaline saponification. The other one appears to be restricted to the malignant tumor and represents a novel melanoma-associated ganglioside derivative. It was characterized as O-acetyl(NeuAc)2-nLc4Cer by exoglycosidase cleavage, by proving its neutral carbohydrate backbone as type II-chain lacto-series oligosaccharide using mouse monoclonal antibody 1B2, and by its cross-reaction with antibody R24 following alkaline treatment. Using antibody R24 and cryopreserved tissue sections of both benign and malignant amelanotic melanomas from albino fishes, it was demonstrated that one of the main melanoma-associated gangliosides, GD3, was exposed predominantly in the malignant tumor. Thus, the chemical nature and even the immunohistochemical localization of the gangliosides in fish melanomas proved to be very similar to those of the known gangliosides in the phylogenetically distant human melanomas.

Animals↗

v-erbB related sequences in Xiphophorus that map to melanoma determining Mendelian loci and overexpress in a melanoma cell line.

Certain genotypes of Xiphophorus harbour an accessory Mendelian gene which following loss, impairment, or insufficiency of its regulatory genes in the germ line, mediates the hereditary capacity to develop neoplasia spontaneously or following induction with initiating and promoting carcinogens. Together with its linked regulatory genes it forms a 'tumor gene-complex' (Tu-complex). We concentrated on accessory sex chromosomal Tu-complexes that are responsible for sex chromosome-linked melanoma formation. Southern analyses of the xiphophorine genome with 15 authentic oncogene probes revealed so far that only three v-erbB related EcoRI fragments comprising 4.9 kb of a certain X-, 11.5 kb of another X-, and 6.7 kb of both a Y- and Z-chromosome are inherited in parallel with the Tu-complex and melanoma formation. They are accessory in the genome, and are highly homologous with each other. The sequence of the X-chromosomal 4.9 kb fragment shows minor but significant differences to that of the invariably present autosomal xiphophorine erbB (x-erbB) fragment of 5.5 kb, indicating that at least two different x-erbB genes coding for different EGF receptors can exist in the fish. Northern analyses showed expression of both genes in a fibroblast cell line, and overexpression of the sex chromosomal x-erbB in a melanoma cell line. The co-segregation of the hereditary trait of melanoma with the sex chromosomal x-erbB fragments, suggests that the accessory x-erbB gene may be responsible for the switch from the normal to the neoplastic state of the pigment cells.

Amino Acid Sequence↗

Biochemical indicators of disordered vitamin D and calcium homeostasis in sarcoidosis.

In an attempt to identify factors that may indicate which patients with sarcoidosis are likely to manifest a clinical abnormality in calcium homeostasis, we measured serum concentrations of calcium, angiotensin converting enzyme activity (ACE), 25-hydroxyvitamin D (25-OH-D), 1,25-dihydroxyvitamin D (1,25-(OH)2-D), and immunoreactive parathyroid hormone (iPTH) in 19 patients with biopsy proven sarcoidosis, seven of whom were either frankly hypercalcemic or hypercalciuric. These data were compared to the ability of cultured pulmonary alveolar macrophages (PAM) from the same patients to metabolize [3H]25-OH-D3 to [3H]1,25-(OH)2-D in vitro. All seven hypercalcemic/hypercalciuric patients with sarcoidosis had a serum ACE level greater than 40 IU/L (normal less than 35 IU/L). All five patients with hypercalcemia (Ca greater than or equal to 10.5 mg/dl) had a serum 1,25-(OH)2-D concentration above the normal range (greater than 60 pg/ml), and in all 19 patients the serum calcium was positively correlated to the serum 1,25-(OH)2-D concentration (r = 0.55, p less than 0.01). The capacity of PAM to synthesize [3H]1,25-(OH)2-D3 in vitro was. with one exception, greater in cells from patients with diffuse infiltrative pulmonary disease (roentgenographic stage II or III) and positively correlated to the serum calcium concentration (r = 0.72, p less than 0.001) and serum ACE (r = 0.43, p less than 0.05). Cultured PAM from the five hypercalcemic patients, all of whom demonstrated diffuse pulmonary disease on chest x-ray, showed a [3H]1,25-(OH)2-D3 synthetic capacity in vitro 2.5-fold greater than that for group as a whole and 6-fold greater than in cells from nonhypercalcemic patients with sarcoidosis.

Calcifediol↗

NMR study of the drug-base overlap geometry in the dark complex of 8-methoxypsoralen and d(pApT)4.

The dark binding of 8-methoxypsoralen (MOP) to d(pApT)4 was investigated by 270-MHz 1H nuclear magnetic resonance (NMR) spectra. The continuous high-field shifts of the MOP resonances by d(pApT)4 at low temperatures indicate fast exchange between free and bound drug. The limiting complexation shifts of the various MOP protons between 0.36 (CH3) and 1.20 ppm (H5) are in the range expected for an intercalation complex. The NMR line widths of the MOP ring protons vary with the square of the observed complexation shifts (maximum at H5), indicating a dominant effect of the fast exchange between free and bound drug. The corresponding kinetic parameters agree with the values previously reported for a variety of other intercalators. The observed exchange broadenings were also used as a criterion to limit the uncertainty connected with fast averaging of the signals of the drug in potential multiple binding modes: A qualitatively different pattern of broadenings (minimum at H5) is expected from fast exchange between the two binding modes related by the short 2-fold quasi-symmetry axis of MOP. The measured complexation shifts were compared to theoretical values calculated on the basis of coplanar intercalation with base pair arrangements derived from typical published intercalation site geometries. The standard deviation between observed and calculated shifts was considerably smaller for asymmetrical intercalation between the bases of the same strand (less than or equal to 0.11 ppm) than for symmetrical intercalation between the base pairs (greater than or equal to 0.28 ppm).(ABSTRACT TRUNCATED AT 250 WORDS)

Darkness↗

Elevated expression of the cellular src gene in tumors of differing etiologies in Xiphophorus.

In the fish Xiphophorus we have detected elevated levels of pp60c-src kinase activity in a variety of tumors (n = 34) of neurogenic, epithelial, and mesenchymal origin either of hereditary etiology or induced by carcinogens. This elevation ranged from 2-fold up to 50-fold compared to the corresponding non-tumorous tissue and up to 6-fold compared to the highest activities found in any of the normal organs. The level of elevation parallels the degree of malignancy in melanoma and in tumors of mesenchymal origin. In fish bearing tumors of hereditary etiology kinase activity was also elevated in the non-tumorous brain, while in fish bearing induced tumors, kinase activity was elevated only in the cells of the neoplasia.

Animals↗

Neurosarcoidosis. A report of ten patients illustrating some usual and unusual manifestations.

The common and not so common neurologic lesions due to sarcoidosis include cranial nerve palsies, meningitis, hypothalamic and pituitary lesions, basilar meningitis, polyneuropathy, space occupying lesions and spinal cord involvement. The diagnosis of neurosarcoidosis requires a compatible clinical or radiologic picture of sarcoidosis and histological confirmation of noncaseating granulomas. Serum ACE, Gallium-67 lung scan and bronchoalveolar lavage are of help in supporting the diagnosis and establishing activity of the disease. A CT scan with enhancement is the diagnostic procedure of choice. Corticosteroids are the cornerstone of therapy.

Adolescent↗

[Prevention of infections in surgery of the colon].

The value of perioperative antibiotic prophylaxis in colorectal surgery is undisputed, since for the first time the rate of wound healing disorders could be reduced from 30 to 50% previously to less than 10%. In 3 prospectively randomized studies different kinds of prophylaxis were tested: short-time prophylaxis over 48 hours, ultra-short time prophylaxis over 24 hours, "one-shot" administration during surgery. The effective spectrum of the used cephalosporines should affect aerobic as well as anaerobic pathogens, as septic complications are caused by intraoperative bacterial dissemination. Cephalosporines such as Cefoxitin, Lamoxactam and Cefotaxime having sufficiently high serum and tissue levels at the time of enterotomy, may be used successfully as a perioperative antibiotic prophylaxis. "One-shot" administration in 100 patients has led to a drastic reduction of wound healing disorders to 4% (four mild wound healing disorders, four anastomotic leaks (9.4%). We prefer the perioperative antibiotic "one-shot" administration not only for this reason, but also because of the lowered possibility for the development of resistances and bacterial selection.

Anti-Bacterial Agents↗

Investigation of the erythema effectiveness curve with tunable lasers.

The erythema effectiveness curve (EEC) has been remeasured with frequency-doubled tunable dye lasers in the wavelength range from 250 to 320 nm. The EEC has been determined from the response of the skin of adult white males after application of a 5 mJ/cm2 radiant exposure. Additionally, minimal erythema doses have been measured. The results confirm earlier observations but give curves with a smaller half bandwidth. In the range from 290 to 310 nm, the EEC has been measured after application of 8-methoxypsoralen and of 3-carbethoxypsoralen.

Adult↗

Investigations on the mechanism of photodynamic action of different psoralens with DNA.

Investigations on the photodynamic action of psoralens with DNA were performed, using experimental techniques of fluorescence lifetime and NMR-CIDNP, as well as SCF-MO and CNDO molecular orbital calculations. It has been shown that the formation of a biradical through the triplet state is the decisive step for psoralen dimer formation, as well as for cyclobutane addition with thymine, while singlet oxygen production is responsible for enzyme inactivation (e.g., lysozyme and trypsin). The molecular orbital calculations, in agreement with experimental results, indicate that the differences in biological effectivity of different psoralens are based on variations in triplet formation probability.

Animals↗

Cytogenetics of neoplasia of Xiphophorus.

Certain laboratory hybrid Xiphophorus fish develop heritable neoplasia. Neoplasia can also be induced in some hybrids by treatment with carcinogens. In either case the neoplasms are mediated by a "'tumor gene," that is normally controlled by linked or nonlinked "regulating genes" or both. Light and electron microscopic studies on these two types of tumors reveal important differences. The heritable tumor is a compact mass of tissue formed of densely packed melanized melanocytes often with nuclear pockets and projections. A large number of cells undergoing a process of nuclear fragmentation has been observed. The induced tumors, on the other hand, contain fewer melanized melanocytes and show a comparative increase in the amount of connective tissue. The nuclear pockets and projections commonly found in the melanocytes of the heritable tumors are not present in the melanocytes of the induced melanoma. The most important difference observed was the presence of different types of structural chromosome aberrations in the induced tumor and a total absence in the heritable ones. These anomalies seem to be epiphenomenal, and the real genetic change is subchromosomal.

Animals↗

[Indwelling venous catheters. Results of a clinical and experimental study].

Six venous indwelling cannulas were observed under constant frame conditions (low osmolar solutions, constant infusion solution, prospective randomized study). There is a close correlation between the complication rate in the vein and quality of the material and puncture. The best results were achieved with Teflon cannulas. Here the condition of the transitional zone between mandrin and synthetic material was of special importance as well as the fact that the form stability also had to be guaranteed after application. The thrombotic dry weights of these cannulas, determined in animal experiments, yielded low values for polytetrafluorethylene (PTFE) or polyethylene (PE), but PTFE and PE cannulas have led to an increase of the thrombotic dry weight in 24 and 48 h of indwelling time.

Animals↗

[On the role of CEA-monotoring in the diagnosis of colorectal carcinomas and recidivations (author's transl)].

The CEA-radioimmune-test is not a specific tumour-detection test, but will rather serve as an indicator of the therapeutic result, the formation of recurrent tumours and/or metastases. The CEA titer increase precedes the occurrence of clinical symptoms by up to 12 months, so that a symptomatic look can take place earlier. 150 patients with colorectal carcinomas were observed over a period of 3 years. This yielded the following findings in dealing with the CEA test: 1. Radical tumour surgery results in a decrease of CEA level to normal values. -- 2. A postoperative reduction of CEA titer and subsequent re-increase signalize the formation of a local recidivation. -- 3. A rapid increase in the CEA level after postoperatively decreased or constant values indicates the formation of metastases. -- 4. The CEA test will only possess its full informational value for postoperative treatment when the titer has been increased preoperatively. -- 5. A pathological CEA titer is no proof of a malignant disease. -- 6. A normal CEA titer never rules out a malignant disease.

Adult↗