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K Worm

Publications and source records attributed to K Worm.

At least 19 recordsLinked to original sources
PubMed2007

Activation of extracellular regulated kinases (ERK1/2) but not AKT predicts poor prognosis in colorectal carcinoma and is associated with k-ras mutations.

Signal transduction and modulation represent central mechanisms in cellular processes such as cell-cycle regulation, oncogenesis, and apoptosis. The aim of this study was to determine the prognostic relevance of two kinases important in the regulation of cell proliferation and apoptosis in 135 colorectal cancer cases: AKT and extracellular regulated kinases (ERK1/2). We investigated the relationship of phospho-ERK1/2 (pERK1/2) and phospho-AKT (pAKT) with associated parameters (EGFR, COX-2, cyclin-D1), proliferative activity (Ki-67), and apoptosis (TUNEL) using immunohistochemistry. Additionally, the k-ras gene was screened for mutations to determine its putative association with ERK1/2 activation. Activation of ERK1/2 but not AKT correlated statistically with the presence of k-ras mutations (P = 0.015). Survival analysis of phospho-ERK1/2 immunoexpression showed a significant correlation with decreased overall survival (OS). The multivariate Cox regression analysis identified pERK1/2 as an independent prognostic parameter (P = 0.005). Activation of ERK1/2 in colorectal cancer may indicate aggressive tumor behavior and may constitute an independent prognostic factor. Furthermore, our data suggest that mutations of the k-ras oncogene may induce activation of ERK1/2. We propose immunohistochemical determination of pERK1/2 status as a promising candidate for the identification of high-risk patients who would benefit from new anticancer drugs targeting the ERK pathway.

Colorectal Neoplasms↗
PubMed2005

ETV6-NTRK3 gene fusion in a secretory carcinoma of the breast of a male-to-female transsexual.

Secretory carcinomas of the breast were first described as "juvenile carcinoma" by McDivitt and Stewart in a cohort of children. This term has been replaced by the term "secretory breast carcinoma", because the entity can occur at any time of life. Carcinoma of the male breast is uncommon and accounts for approximately 1% of all cancers in men. Recently, it has been reported that human secretory breast carcinoma expresses the ETV6-NTRK3 gene fusion that was previously cloned in pediatric mesenchymal cancers. We present the case of a 46-year-old male-to-female transsexual in whom a secretory breast carcinoma was an incidental finding. As confirmation of the histopathological diagnosis we detected the novel ETV6-NTRK3 gene fusion in this tumor.

Breast Neoplasms, Male↗
PubMed2000

[Substances other than alcohol found in the blood among Danish road-users during a week in 1996].

INTRODUCTION: This investigation is the Danish contribution to a Nordic comparative study of other drugs than alcohol found in road users. MATERIAL AND METHODS: 255 blood samples received from the police for alcohol and/or drug determination during one week in 1996 were investigated for drugs. RESULTS: 56 (22%) of the 255 blood samples were positive for other drugs than alcohol. Cannabis was detected in 11%, benzodiazepines, mainly diazepam and flunitrazepam, in 9% and amphetamine in 5% of the blood samples. DISCUSSION: The police suspected other drugs than alcohol in 3% of the 255 blood samples, but drugs were detected in 22%. This investigation showed that the frequency of other drugs than alcohol was similar in Denmark and Norway for the blood samples with an alcohol concentration above the statutory limit. This contrasts with the fact that the number of blood samples from road users investigated for substances other than alcohol is about 200/year in Denmark and 4000/year in Norway.

Accidents, Traffic↗
PubMed2000

[Fatal intoxications among drug addicts in Denmark in 1997].

INTRODUCTION: The purpose of this study was to investigate fatal poisonings among drug addicts in 1997 and to compare the results to similar investigations from 1985 and 1991. MATERIAL AND METHODS: All fatal intoxications among drug addicts in Denmark in 1997, investigated at the three Institutes of Forensic Medicine in Denmark. RESULTS: The number of fatal intoxications increased by 32% from 1991 to 1997, mainly outside the metropolitan area, The average age increased from 32 to 36 years. The proportion of heroin/morphine intoxications increased from 57% to 71%. The most commonly used drugs were as in 1991 heroin/morphine, diazepam and methadone. The frequency of cocaine increased from one positive case in 1991 to 14% positive cases in 1997. DISCUSSION: This study showed an increasing number of fatal intoxications and changes in drug abuse pattern and place of death since 1991.

Adolescent↗
PubMed1999

[Fatal poisonings during a 5-year period in Eastern Denmark].

In the period 1992-1996, both years included, 1079 cases of deaths from poisoning by drugs or poisons were found by forensic-chemical analyses at The Institute of Forensic Medicine, Dept. of Forensic Chemistry, in Copenhagen, covering a population of 2.4 million. Morphine was by far the most frequently occurring compound accounting for 421 deaths, followed by methadone with 185 deaths. Then alcohol, ketobemidone, and carbon monoxide were represented with 80, 74 and 66 deaths, respectively. Drug addicts dominated in the survey with 549 cases. According to Danish law, autopsy with following chemical analyses must be performed on all dead drug addicts, whereas many other deaths by poisoning are defined only from the medicine found in the vicinity of the dead body.

Adolescent↗
PubMed1999

[Citalopram in forensic samples. Citalopram concentrations in samples from legal autopsies and from living persons in connection with traffic accidents or cases of violence in Denmark 1989-1996].

Citalopram was found in 92 autopsy cases and 27 cases from living persons and the concentrations are described. A range of 6.2-19 mumol/kg whole blood was found in cases where citalopram alone was the cause of death and a range of 1.9-16 mumol/kg whole blood in cases, where citalopram together with other compounds were considered to be the cause of death. In autopsy cases toxic concentrations were in the range 1.2-2.8 mumol/kg whole blood and concentrations between 0:09 and 1.9 mumol/kg were considered therapeutic. In cases from living persons the citalopram concentrations in whole blood were 0.06-0.9 mumol/kg.

Accidents, Traffic↗
PubMed1999

Reverse transcriptase polymerase chain reaction as a reliable method to detect epidermal growth factor receptor exon 2-7 gene deletion in human glioblastomas.

Epidermal growth factor receptor (EGFR) gene amplification has been reported to occur in diverse carcinoma types such as lung, ovarian, and breast carcinomas and in glioblastomas. A 801-bp in-frame deletion close to the aminoterminus of the receptor protein has been found to occur more or less frequently within at least three of these tumor entities. We studied EGFR gene alterations using the polymerase chain reaction and EGFR gene expression of 65 astrocytic tumors (51 glioblastomas World Health Organization [WHO] IV, five anaplastic astrocytomas WHO III, and nine astrocytomas WHO II). EGFR gene amplification, as determined by Southern blotting using a full-length cDNA probe, was observed in 22 of 51 glioblastomas (43%) but in none of the grade II astrocytomas. Two of five anaplastic astrocytomas at WHO III showed a considerable degree of EGFR amplification but, according to the neuroradiological data, these two tumors had to be considered as glioblastomas. The most frequently found genetic alteration was the 801-bp deletion near the receptor aminoterminus comprising a complete loss of exon 2 to exon 7 (del2-7). We showed that RT-PCR is superior to Southern blot analysis in detection of this type of deletion and can be assigned to 9 of 38 (24%) glioblastomas examined. Expression of a EGF receptor protein was enhanced in most of the tumors with gene amplification. However, 5 of 18 tumors that express a receptor protein in the absence of EGFR gene amplification also showed elevated levels of EGFR gene expression. In addition to the full-length receptor protein, a signal in the 140-kDa range was observed in 17 of 35 glioblastomas (49%). This fragment may correspond to the truncated de12-7 receptor protein or might be due to proteolysis of the full-length receptor protein.

Blotting, Southern↗
PubMed1998

[Drug and narcotic use among Danish drivers].

An investigation was made of the presence of drugs and narcotics in samples from Danish drivers having violated the Danish Road Traffic act in 1993. Four hundred and twenty-five cases were received, but only 317 cases were analysed for drugs or narcotics. In 256 cases drugs or narcotics were found present with a total of 531 findings. In 112 of the cases only one compound was found present. Benzodiazepines, morphine, methadone, cannabinoids and amphetamine were the most frequently occurring compounds with 239, 52, 42, 32 and 28 findings, respectively. The study has shown that especially the benzodiazepines together with the illicit drugs seem to constitute a threat to traffic safety. For two countries very much alike, namely Denmark and Norway this study has shown a remarkable difference in the number of samples analysed and the results found.

Adult↗
PubMed1998

Citalopram concentrations in samples from autopsies and living persons.

Concentrations of citalopram in medicolegal samples from 92 autopsies and 27 living persons are described. In autopsy cases in which citalopram alone was the cause of death, concentrations ranged from 2.0 to 6.2 mg/kg whole blood. In autopsy cases in which citalopram together with other substances was considered to be the cause of death, the concentrations of citalopram ranged from 0.6 to 5.2 mg/kg whole blood. In autopsy cases toxic concentrations ranged from 0.4 to 0.9 mg/kg whole blood and therapeutic concentrations from 0.03 to 0.6 mg/kg whole blood. In samples from living persons the concentrations of citalopram in whole blood were 0.02 to 0.3 mg/kg.

Adult↗
PubMed1997

Primary structure of locust opsins: a speculative model which may account for ultraviolet wavelength light detection.

The sequences of two locust opsins have been determined by dideoxy nucleotide sequencing of PCR products from cDNA derived from eyecup tissue. The opsins (Lo1 and Lo2) are encoded by 381 and 380 amino acid residues, respectively, with hydropathy profiles and placement of key amino acid residues suggestive of a typical seven-transmembrane rhodopsin structure. The sequence alignment of Lo1 reveals significant homology to mantid opsin. These opsins contain retinal as their visual chromophore and have similarity to the Rh1 type sequences from Drosophila and Calliphora which use 3-hydroxy retinal. Lo2 is most closely related to the Rh3/4 type of visual pigments from Drosophila. The retinal-based opsins show reduced numbers of charged amino acids in the loop region connecting transmembrane segments V and VI compared to the 3-hydroxy retinal opsins. Sequence alignment of all the known insect visual pigments has shown that only those with maximal sensitivity in the blue/UV spectral range, Lo2 and the Rh3/4 opsins of Drosophila, have three charged amino acids in transmembrane segments II, IV and VII. The charged residue in transmembrane VII is two helical turns away from the positively charged Schiff base and could act directly as a counterion to it. From the secondary structure analysis of opsin, the two charged residues in transmembrane II and IV would be in close proximity to form a dipole. These polar motifs in Lo2 and Rh3/Rh4 could act in wavelength modulation of short wavelength sensitive pigments and substantiate the proposed external two-point charge model which accounts for the spectral sensitivity of visual pigments [Honig, B., Dinur, U., Nakanishi, K., Balogh-Nair, V., Gawinowicz, M.A. and Motto, M. (1979). Journal of the American Chemical Society, 101, 7084-7086].

Amino Acid Sequence↗
PubMed1996

Influence of expression system on chromophore binding and preservation of spectral properties in recombinant phytochrome A.

N-Terminal deletion mutants of the plant photoreceptor phytochrome, additionally truncated at two different positions at their C-terminal ends, were expressed both in Escherichia coli and in yeast (Pichia pastoris) and converted into chromoproteins upon chromophore incorporation. The start and end positions of the cDNA employed (phyA from oat) mimic the positions of tryptic cleavage (deletion of the first 64 amino acids, and stop codons after amino acid positions 425 or 595, generating 39-kDa and 59-kDa peptides, respectively. The absorption properties and photochromicity upon red/far-red irradiation of these mutants were compared with their tryptic counterparts derived from native oat phytochrome and with recombinant products possessing intact N-termini, but C-terminal positions identical to those of the corresponding tryptic fragments (45-kDa and 65-kDa peptides). All recombinant 65-kDa and 59kDa peptides bound the chromophore after expression and showed the appropriate absorption spectra of the Pr and the Pfr forms. The smaller chromopeptides (45-kDa and 39-kDa) behaved differently depending on the expression system employed. E. coli-derived peptides exhibited a phytochrome-like difference spectrum only when the intact N-terminus was present (45-kDa product). The recombinant 39-kDa peptide from E. coli was incapable of chromophore binding whereas the identical peptide sequence expressed by P. pastoris formed a chromoprotein with phycocyanobilin. This recombinant phytochrome fragment exhibited a difference spectrum (Pr-Pfr) with an even larger Pfr absorption band than the comparable tryptic 39-kDa fragment. Selectivity of chromophore incorporation and spectral properties suggest that interactions between protein domains of phytochrome control the protein folding and the Pr/Pfr absorption characteristics. Evidently, trypsin digestion down to the 39-kDa fragment affects protein conformation also in terms of Pfr conservation.

Avena↗
PubMed1996

Drugs in blood samples from unconscious drug addicts after the intake of an overdose.

This investigation includes whole blood samples from 53 drug addicts found unconscious in the Copenhagen area with evidence of a heroin overdose. Heroin/morphine was detected in 85% of the patients and other opioids in 11%. One or more benzodiazepines, most often diazepam, were detected in 75% of the patients. A blood alcohol concentration higher than 1.00 mg/g was detected in 57% of the patients. Methadone was detected in seven patients, ketobemidone in four, amphetamine in five and cocaine in one. This investigation showed widespread multi-drug abuse and heroin/morphine alone was detected in only one patient. As indicators of heroin intake, 6-mono-acetylmorphine (MAM) and morphine were detected in this investigation.

Adult↗
PubMed1996

Chromophore-protein interaction controls the complexity of the phytochrome photocycle.

A new protocol for the preparation of recombinant phytochromes results in significantly higher yields which, for the first time, have made kinetic studies possible. Flash photolysis with nanosecond laser excitation reveals that, in recombinant and native phytochromes, the decay kinetics of the primary photoproducts I700i and the kinetics of the formation of the Pfr form are similar. Phycocyanobilin-containing recombinant phytochrome, however, shows only a monoexponential decay of the I700 intermediate with a time constant of approximately 90 microseconds, and a biexponential formation of the Pfr form, albeit with time constants (approximately 13 and 100 ms) somewhat shorter than those from native phytochrome. Thus the seemingly small structural modification of the chromophore (substitution of the native vinyl for an ethyl group) has a profound influence on the availability of protein conformational rearrangement pathways. The result is therefore of general interest in chromoprotein dynamics.

Amino Acid Sequence↗
PubMed1994

[Deaths among drug addicts in Denmark. A forensic medical study of deaths among drug addicts during the period 1991-1992 related to the period 1984-1985].

This study includes all deaths among drug addicts in the years 1991 (n = 219) and 1992 (n = 214) investigated at the three institutes of forensic medicine in Denmark. The results are compared with deaths among drug addicts in 1984-1985. The number of deaths among drug addicts increased by approximately 50% in 1991-1992 compared with 1984-1985. The increase was most significant among drug addicts over 35 years of age. The cause of death was intoxication in three-quarters of the cases in 1991-1992. In half of these cases heroin/morphine had caused death, while intoxications caused by methadone accounted for approximately 30% of the cases. In the metropolitan area the frequency of methadone intoxications increased significantly compared with 1984-1985, whereas the number of heroin/morphine intoxications did not change. Outside the metropolitan area, however, a significant increase in heroin/morphine intoxications was noticed. In all parts of the country the number of propoxyphene intoxications decreased to a few annual cases. The most commonly used drugs of abuse were heroin/morphine, diazepam and methadone, often in combination with alcohol.

Adolescent↗
PubMed1994

Deaths among drug addicts in Denmark in 1987-1991.

In the period 1987-1991 a total of 739 fatalities among drug addicts was investigated at the three University Institutes of Forensic Medicine in Denmark. The annual number rose from 130-140 in the first 4 years to 192 in 1991, and 80% were males. The mean and median age for both males and females increased by 1 year in the period. The main drug of abuse was heroin, in most cases supplemented by various other drugs, and in almost all cases taken intravenously. In about one-third of the cases each year there was information of abuse of alcohol in addition. In the poisoning cases, the main drug of poisoning was morphine/heroin, constituting 35-55% of the cases each year. As regards methadone-poisoning cases, the number increased significantly in 1991 compared to the first 4 years. Furthermore, the number and proportion of addicts dying while in methadone treatment increased during the 5-year period. In about half of the methadone poisoning cases, there was information of methadone treatment at the time of death. The other half obviously obtained the methadone completely illegally. Ketobemidone was the third most frequent drug of poisoning, while propoxyphene and barbituric acid only were found in a very few cases each. The results are compared to those from an earlier investigation concerning drug deaths in Denmark in 1968-1986. The importance of registering drug deaths is emphasized.

Adolescent↗
PubMed1994

[Fatal poisonings in Eastern Denmark 1984-1991].

From 1984 to 1991, both years included, 1884 cases of deaths from poisoning by drugs or poisons were found by the forensic chemical analyses at the Institute of Forensic Chemistry in Copenhagen, covering a population of 2.3 million. Most deaths occurred in the age group 30-39 years. Looking at the period as a whole, morphine was by far the most frequently occurring compound followed by propoxyphene, carbon monoxide, methadone and alcohol. However, looking at the annual distribution, the number of deaths due to propoxyphene declines over the period, while the number of deaths due to methadone increases. Barbiturate poisonings, which were formerly among the most frequently occurring, are only seen in low numbers.

Adolescent↗
PubMed1993

[Methadone and drug addicts].

Dead drug addicts from Copenhagen City and County in 1981 and 1989 respectively were analysed for methadone. Ninety-four cases from 1981 and 70 cases from 1989 were analysed; from 1981, 16% were found positive for methadone, while in 1989, 37% were positive. Methadone alone was found to be the cause of death in 50% more cases in 1989 than in 1981. Only half of the methadone positive dead drug addicts had been in methadone treatment. Morphine and benzodiazepines were the most frequently occurring other substances in both 1981 and 1989. Alcohol was found present in only about 30% of the methadone-positive cases. Medians for methadone whole blood conc. were 0.9 mumol/kg with no alcohol present and 0.5 mumol/kg with alcohol present in addicts dying from methadone. In living persons using methadone, the median was 0.4 mumol methadone/kg whole blood with no alcohol present and 0.3 mumol/kg with alcohol present.

Adolescent↗