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Biomedical subjects

K Marien

Publications and source records attributed to K Marien.

13 recordsLinked to original sources

Contact allergy to isothiazolinone derivatives: unusual clinical presentations.

Contact allergic reactions to the mixture of 5-chloro-2-methyl-4-isothiazoline-3-one and 2-methyl-4-isothiazoline-3-one are most frequently associated with intolerance to cosmetics. The present article points out that such reactions, particularly on the face, can have unusual clinical presentations that are very similar to seborrheic eczema, lupus erythematosus, lymphocytic infiltrate or photodermatitis. Atopic dermatitis is also often erroneously suspected.

Adult

Expression of ras genes in rainbow trout liver.

Members of the ras gene family have been studied in a variety of species. Two ras genes expressed in the normal liver of rainbow trout, ras-1 and ras-2, as well as a portion of a genomic ras-1 allele, are described for the first time in this report. Over 500 bp of trout ras-1 and at least 300 bp of trout ras-2 genes expressed in normal liver have been sequenced; DNA homology to the human ras genes ranges from 76.8% to 87.1%. The base changes resulting from over 400 million years of evolutionary divergence between the species were primarily silent, with few changes in protein sequence. The partial DNA sequence of the genomic ras-1 allele has 86.8% homology to the first two exons of human c-Ha-ras, and its intron has several conserved sequences characteristic of vertebrate intron-exon junctions. However, the predicted amino acid sequence of trout ras-1 differs at only one of the first 172 amino acid residues from human c-Ki-ras with the alternate exon 4b. Since trout ras-1 differs at 17 and 18 residues from the human c-N-ras and c-Ha-ras proteins, respectively, over this region, we conclude that trout ras-1 is a c-Ki-ras gene. The highly conserved nature of this gene suggests that the ras p21 protein has identical functions in normal and neoplastic cells among higher and lower vertebrates.

Animals

Analysis of ras gene mutations in rainbow trout liver tumors initiated by aflatoxin B1.

The suspect human hepatocarcinogen aflatoxin B1 (AFB1) is a well-known potent initiator of hepatic tumors in rainbow trout (Oncorhynchus mykiss). Both hepatocellular carcinomas and mixed hepatocellular/cholangiocellular carcinomas are induced by AFB1 in trout, with the mixed form predominating. We previously isolated two c-ras genes from trout liver cDNA, and in the present study we analyzed DNA from 14 AFB1-induced trout liver tumors for point mutations in exon 1 of both genes. Using the polymerase chain reaction (PCR) and oligonucleotide hybridization methods, a high proportion (10/14) of the AFB1-initiated tumor DNAs showed evidence of activating point mutations in the trout c-Ki-ras gene. Of the 10 mutant ras genotypes, seven were codon 12 GGA----GTA transversions, two were codon 13 GGT----GTT transversions, and one was codon 12 GGA----AGA transition. Nucleotide sequence analysis of cloned PCR products from four of these tumor DNAs provided definitive evidence for two codon 12 GGA----GTA mutations, one codon 12 GGA----AGA mutation, and one codon 13 GGT----GTT mutation, in complete agreement with the oligonucleotide hybridization results. No mutations were detected in exon 1 of a second trout ras gene also expressed in liver, nor in DNA from control livers. This is the first report of experimentally induced ras gene point mutations in a lower vertebrate fish model. The results indicate that the hepatocarcinogen AFB1 induces c-Ki-ras gene mutations in trout similar to those in rat liver tumors.

Adenoma, Bile Duct

Alterations of hepatic acetyl-CoA carboxylase by 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on acetyl-CoA carboxylase (ACC) activity and synthesis was examined. Male Wistar rats received a single i.p. injection of TCDD (53 micrograms/kg), and nine days later body weight, liver weight, hepatic lipid, ACC activity and mass were determined and compared to pair-fed controls. Body weights of TCDD-treated animals decreased, while liver weights increased resulting in an increase in liver to body weight ratios. ACC activity was decreased by 65%, however sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Western analysis using a biotin specific probe revealed that ACC protein levels were not appreciably changed. In addition, there was a large increase in exogenous lipid material in TCDD-treated livers as determined by osmium tetroxide staining. These data suggest that the decrease in ACC activity may be due to direct inhibition of the enzyme by negative allosteric interactions with free fatty acids released from adipose tissue that subsequently accumulate in liver.

Acetyl-CoA Carboxylase

Isolation and identification of acetyl-CoA carboxylase from rainbow trout (Salmo gairdneri) liver.

Acetyl-CoA carboxylase is the pivotal enzyme in the de novo synthesis of fatty acids and is the only carboxylase with a biotin-containing subunit greater than 200,000 daltons. The biotin moiety is covalently linked to the active site and has a high affinity (Kd = 10(-15) M) for the protein avidin. This relationship has been used in previous studies to identify acetyl-CoA carboxylase isolated from mammalian species. However, acetyl-CoA carboxylase has not been isolated and characterized in a poikilothermic species such as the rainbow trout. The present study describes the isolation and identification of acetyl-CoA carboxylase in the cytosol of rainbow trout (Salmo gairdneri) liver. The enzyme was isolated using two distinct procedures--polyethylene glycol precipitation and avidin-Sepharose affinity chromatography. Identification of the isolated protein as acetyl-CoA carboxylase was made by the following: (1) sodium dodecyl sulfate-polyacrylamide gel electrophoresis; (2) avidin binding; (3) in vivo labeling with [14C]biotin; and (4) acetyl-CoA carboxylase-specific activity. The subunit molecular weight of the major protein was 230,000 daltons +/- 3.3%. This protein was shown to bind avidin (Mr = 16,600) prior to sodium dodecyl sulfate-polyacrylamide gel electrophoresis, indicating the presence of biotin. In addition, protein isolated from fish that had previously received intraperitoneal injections of [14C]biotin, showed the majority of radioactivity associated with the 230,000 dalton protein.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl-CoA Carboxylase

Characteristics of site variation among clones of the 340-base pair, tandemly repeated EcoR1 family of human DNA.

Twenty-four clones of EcoR1-restricted, 340-base pair (bp) DNA derived from human DNA have been sequenced and compared to a published consensus sequence for this family. No two clones were found to have identical sequences; the clones studied differed from the consensus sequence in as few as 1 or as many as 41 sites. On the average in these clones, a 5.2% divergence from exact homology was found, with 1 of 10 of the site variations being "nonrandom," i.e., cases in which five or more clones had the same nucleotide substitution at that site (viz., 53, 124, 126, 138, 152, and 157). At site 157, for example, 16 of the 24 clones differed from the reference sequence. Positions and their respective changes, as compared to the consensus sequence, are summarized. Variations are discussed with relation to possible functions for these sequences.

Base Sequence

T-helper cell lymphoma involving the lymph nodes and skin. A clinical, morphologic, and immunohistochemical analysis of five cases.

The clinical, morphologic, and immunohistochemical features of 5 cases of peripheral T-cell lymphoma with lymph node and skin involvement are reported. All patients were male and presented with generalized lymphadenopathy and skin lesions. Lymph node biopsy specimens showed a diffusely growing, pleomorphic, atypical lymphoid infiltrate composed of markedly irregular small and large cells. The stroma consisted of plasma cells, eosinophils, epithelioid histiocytes, and an increased number of small blood vessels. A similar neoplastic infiltrate was observed in the cutaneous nodules that developed in three patients. Immunohistochemistry on frozen tissue sections of lymph nodes using a broad panel of monoclonal antibodies revealed that the neoplastic cells were reactive with anti-T-cell antibodies, the majority of them belonging to the helper/inducer T-cell subset. Stromal plasma cells contained polyclonal immunoglobulins. It is concluded that the malignant lymphoma of peripheral helper/inducer T-cell origin observed in these five patients represents a variant of a mixed, blastic/cell T-cell lymphoma, characterized by a peculiar stromal component and skin involvement.

Aged

The histology of eccrine poromas: a study of 14 cases.

A histological study of 14 eccrine poromas in 14 different patients was conducted and the results correlated with the clinical data. Histologically, an eccrine poroma is an easily recognizable epithelial skin tumor. Three morphological variants can be identified: a benign, a premalignant or dysplastic, and an invasive, malignant form. These tumors hardly have a typical clinical appearance. Symptoms such as bleeding, pain and itching are suggestive of a possible malignant transformation. There seems to be a predilection for localization on the limbs and the head. Most of the lesions occur in patients above the age of 60. It is noteworthy that these tumors, at least those of the face, occur on actinically damaged areas.

Adenoma, Sweat Gland

A cutaneous APUDoma or Merkel cell tumor? A morphologically recognizable tumor with a biological and histological malignant aspect in contrast with its clinical behavior.

Clinical, microscopic, ultrastructural, and histochemical characteristics of a primary cutaneous tumor, identified as an APUDoma possibly arising from Merkel cells, are presented. The tumor can be diagnosed by means of routine histology. In some cases the argyrophylic staining technique can be helpful. The dermatological and histological aspects of this tumor suggest a highly malignant undifferentiated process. The biological behavior of this tumor, however seems to be of a low-grade malignancy. It is therefore important to recognize it from undifferentiated, highly malignant, mostly metastatic processes in the skin. There is also a summary of the clinical history and microscopic findings of identical tumors in 4 other patients.

Aged

Further observations on periodicities of nucleotide occurrences in natural DNA's.

There are non-random features in the occurrences of nucleotides in the DNA's of certain organisms which are detectable by statistical analyses of the entire sequence. Earlier, using the bacteriophage Phi-X 174 DNA sequence, we had reported that the self-information values for one type of dinucleotide association showed a marked periodicity when their autocorrelation coefficients were graphed. A similar, but computationally simpler, analysis has been developed which gives a comparable indication of periodicity. The difference, in average autocorrelation coefficients obtained with this analysis, between the peak values and all others has been used as an index to compare the extent of periodic non-randomness for a series of natural DNA sequences and for various artificial sequences. Calculations show that triplet periodicity, the relationship between dinucleotides separated by a single nucleotide, is characteristic only of the natural sequences of certain filamentous phages and is not found prominently in any other DNA analyzed (including sequences of similar length from plasmids, yeast, bacteria and higher animals). By shuffling nucleotides in a given sequence or by substituting selected nucleotides to alter various positions in both periodic and aperiodic sequences, we have found that an excess or deficiency of a given nucleotide at one of the three positions in a triplet reading frame can simulate the periodic characteristic. Thus, it appears that this global statistical analysis detects the tendency for single-strand phages to utilize a specific nucleotide, rather than one randomly selected, to constitute codons.

Bacteriophage phi X 174