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K Koehler

Publications and source records attributed to K Koehler.

At least 19 recordsLinked to original sources
PubMed2006

Cellular localization of 17 natural mutant variants of ALADIN protein in triple A syndrome - shedding light on an unexpected splice mutation.

The triple A syndrome is a complex and multisystemic autosomal recessive disease with the 3 main symptoms of adrenal insufficiency, alacrima, and achalasia accompanied by neurological impairment. Mutations in the AAAS gene on chromosome 12q13 are responsible for the disorder. AAAS encodes a protein named ALADIN, which belongs to the family of WD-repeat-containing proteins and has been shown to localize to nuclear pore complexes. The function of the protein is not clear. It is supposed that ALADIN plays an important role in RNA and (or) protein trafficking between the nucleus and cytoplasm. With transfection experiments, we analyzed the cellular localization of the wild-type and 17 natural mutant variants (9 missense, 5 nonsense, 3 frameshift mutations) of ALADIN. We show that most mutations cause mislocalization of the mutant ALADIN proteins in the cytoplasm. In contrast, some variants with mutations located at the N-terminus (Q15K, L25P) and 3 artificial C-terminus mutations (Q490X, R493X, and V497X) remain at the nuclear pore. Using a patient cell line, we show that the mutation 43C>A in exon 1 does not cause a missense mutation Q15K but, rather, results in aberrant splicing.

Addison Disease↗
PubMed2005

Facing the genetic heterogeneity in neuromuscular disorders: linkage analysis as an economic diagnostic approach towards the molecular diagnosis.

The identification of an ever increasing number of gene defects in patients with neuromuscular disorders has disclosed both marked phenotype and genotype variability and considerable disease overlap. In order to offer an economic strategy to characterise the molecular defect in patients with unclassified neuromuscular disorders, we designed DNA marker sets for linkage analysis of 62 distinct neuromuscular disorders gene loci, including all known muscular dystrophies, congenital myopathies, congenital myasthenic syndromes and myotonias. Genotyping of marker loci of 140 clinically well-characterised families with unclassified neuromuscular disorders reduced the number of candidates to one or two genes in 49 % of the families. Subsequent mutation analysis and genome-wide scans enabled the determination of the genetic defect in 31 % of the families including the identification of a new gene and a new mutation in an unexpected candidate gene. This highlights the effective application of this approach both for diagnostic strategies as well as for the identification of new loci and genes.

DNA Mutational Analysis↗
PubMed2004

The triple A syndrome is due to mutations in ALADIN, a novel member of the nuclear pore complex.

The triple A syndrome (MIM#231550) is a rare autosomal recessive disorder characterized by adrenocorticotropic hormone (ACTH) resistant adrenal failure, achalasia, alacrima, and a variety of neurological and dermatological features. The triple A syndrome is caused by mutations in the AAAS gene, which encodes a protein known as ALADIN (ALacrima Achalasia aDrenal Insufficiency Neurologic disorder). ALADIN is a new WD-repeat protein that has no significant homology to any previously identified WD-repeat protein. It has been shown that it colocalizes with nuclear pore complexes (NPCs), a finding that strongly suggests an involvement of ALADIN in nucleocytoplasmic transport. An investigation of 110 families with triple A syndrome disclosed mutation hot spots including Q15K (exon 1), and S293P (exon 8), which occur in 17 and 21 families from different geographical regions, respectively. The variable phenotype of all patients cannot be correlated with the localization and the nature of the ALADIN mutations. Thus, modifying genes/factors may be involved in the progression of this neurodegenerative disease. The lack of AAAS mutations in eight patients and negative linkage to chromosome 12q13 in three families are suggestive of genetic heterogeneity. To examine the cellular localization of ALADIN mutants causing triple A syndrome, we investigated nine different ALADIN-mutants: 2 nonsense (W84X, Q456X), 2 frameshift (F157fsX171, G397fsX414) and 5 point mutations (Q15K, L25P, H160R, S263P, L381R) by transfection experiments with green fluorescence protein. Mutants were predominantly localized in the cytoplasm, but also found in the nucleus indicating that ALADIN is essential for NPC targeting. To investigate physiological functions of ALADIN in vivo, we generated and analysed Aaas-/- knockout mice by homologous recombination in embryonic stem cells. Surprisingly, required animals lack any gross abnormality in adrenal and nervous system function. Further studies have to investigate the role of ALADIN at NPCs and to identify interacting proteins. Functional analyses of ALADIN may permit further understanding of its role for adrenocortical function and neurodevelopment.

Adrenal Gland Diseases↗
PubMed2003

Undesirable reactions of domestic pigeons to vaccination against paramyxovirus type 1.

Subcutaneous vaccination of fancy and racing pigeons with inactivated oil-based vaccines protects against all clinical manifestations caused by the Paramyxovirus type 1. Correct application of the vaccine may occasionally result in the development of granulomas or abscess-like lesions on the site of vaccine application. Although protected against disease as proven by challenge experiments, a variable proportion of vaccinated pigeons do not react with the formation of detectable serum antibodies. The pathogenesis of granuloma and abscess-like lesion developments and the failure to form humoral antibodies are presently not understood. Questions relating to legal liability of vaccinating veterinarians are briefly discussed.

Abscess↗
PubMed2001

Heck reaction catalyzed by PD-modified zeolites.

[Pd]-exchanged NaY zeolites have been prepared, characterized, and applied for the first time for catalytic carbon-carbon coupling reactions. The catalysts exhibit a high activity and selectivity toward the Heck reaction of aryl bromides with olefins for small palladium concentrations (< or =0.1 mol % of Pd). The catalysts can easily be separated from the reaction mixture and reused after washing without loss in activity. No limitation to the diffusion of adducts in the zeolite cages was observed (for linear alkenes). The electronic nature of the aryl bromides and the olefins has a dominating effect on the reaction yield and selectivity. The heterogeneous catalysts quantitatively convert all types of all aryl bromide (complete conversion of bromobenzene within 30 min) and activated aryl chlorides under standard reaction conditions. Product form selectivity is observed in the Heck reaction with cyclic olefins.

Journal Article↗
PubMed2000

Hox11 is required to maintain normal Wt1 mRNA levels in the developing spleen.

Mice deficient in Hox11 are asplenic. As Hoxll can function as a transcription factor, we examined the spatial and temporal mRNA expression patterns of Hox11 and a candidate target gene, the Wilm's tumor gene Wt1, in the developing spleen. Hox11 mRNA first appears at approximately dE10.5 in the dorsal mesogastrium while Wt1 mRNA is expressed from dE11.5, approximately 24 hours after Hox11 mRNA first appears. Wt1 mRNA was significantly reduced in the spleen anlage of Hox11-null mice suggesting that Wt1 acts downstream of Hox11 in a transcriptional cascade. Additionally, Hox11 protein is able to transactivate the WT1 promoter in a Hox11-null fibroblast cell line. As Wt1-null embryos have recently been reported to be asplenic, these findings suggest that Wt1 and Hox11 may be components common to a genetic hierarchy that is required for spleen development.

Animals↗
PubMed1999

Feline infectious peritonitis presenting as a tumour in the abdominal cavity.

This paper describes six cases of feline infectious peritonitis (FIP) in which an abdominal tumour had been suspected clinically. Pathological changes were mainly restricted to the massive enlargement of a mesenteric lymph node due to necrogranulomatous lymphadenitis. FIP was diagnosed on the basis of the immunohistological demonstration of coronavirus antigen in intact macrophages within the necrogranulomatous lesions. In the affected lymph node lymphoid tissue was either almost completely effaced or restricted to follicles composed mainly of variable numbers of blasts. From one to many plasma cells positive for coronavirus-specific antibodies were present in the marginal sinuses or capsules. In addition, necrogranulomas were present in the gut-associated lymphoid tissue of the caecum of one cat, and adjacent to the affected lymph node of another.

Abdominal Neoplasms↗
PubMed1998

Prevalence of proteinuria/microalbuminuria in an elderly urban, biethnic community.

INTRODUCTION: The purpose of this study was to compare the prevalences of urinary abnormalities, notably proteinuria and microalbuminuria, in a randomly selected, biethnic population of Hispanic and nonHispanic white males and females and to determine the effects of diabetes, hypertension, and coronary heart disease on these prevalence rates. METHODS: A survey of health and health related issues was conducted on 883 volunteers, mean age 74.1 years, selected randomly from the Medicare rolls of Bernallilo County (Albuquerque), New Mexico. The sample consisted of nearly equal numbers of Hispanic and nonHispanic white males and females. A dipstick urinalysis and test for microalbuminuria was performed on a clean void, untimed urine sample as a part of a 4-hour interview/examination. RESULTS: Of the 696 participants with complete databases, 10.5% had 1+ or greater proteinuria (30 mg/dL or more) by convential urinalysis dipstick and 19.8% had microalbuminuria (50 mg/L or more) by Micral Chemstrip methodology. Participants with diabetes mellitus (Odds Ratio (OR) 2.54, Confidence Interval (CI) 1.71-3.76, p < 0.001), and/or hypertension (OR 2.09, 95% CI 1.46-3.01, p < 0.001) were more likely to have microalbuminuria than participants without either of these conditions. After adjusting for the presence of diabetes and hypertension, there was a trend toward an increased prevalence of coronary heart disease (OR 1.23, 95% CI 0.84-1.81 p = 0.28) in those with microalbuminuria, but this did not reach levels of statistical significance. CONCLUSIONS: Hispanics, even after adjusting for a higher prevalence of diabetes, and for small differences in prevalences of hypertension and coronary heart disease, had more microalbuminuria than nonHispanic whites, and males had more microalbuminuria than females.

Aged↗
PubMed1993

[The "anxiety" ambulatory clinic: development and outlook].

The study herewith represents the conception of the Bonn "anxiety"-ambulance, which was established in the University of Bonn, Department of Psychiatry, in January 1991. Besides we report our experiences from the first four months after opening of our ambulance and present first results.

Agoraphobia↗
PubMed1990

Lycanthropy and demonomania: some psychopathological issues.

Modern reports on lycanthropy mainly concentrate on the content of patients' beliefs in being transformed into an animal. By contrast, an interest in the form of the symptomatology is usually minimal. This paper draws on Karl Jaspers' phenomenological views and focuses on some important albeit neglected psychopathological issues related to form which are relevant to any comprehensive consideration of lycanthropic phenomena.

Awareness↗
PubMed1990

[Psychopathology of person misidentification--a multidimensional concept].

The misidentification of person or Personenverkennung (PV) is provisionally redefined in this paper by focusing on four important points of view offered by German-speaking authors, all more or less based on an analysis of content. These deal with the extent of "craziness" of a PV (Leonhard), the degree of personal relationship of the person misidentified with respect to the patient (Kahlbaum/Pauleikhoff), the extent of the incorrect identification (Jaspers), and, lastly, the stage of stability shown by a PV at a particular point in time (Conrad). On this basis it is suggested that it may be best to initially call the PV simply a "delusion" with all further differentiation of types of PV carried out in light of a multidimensional psychopathological model utilizing various combinations of these four aspects of content.

Capgras Syndrome↗
PubMed1989

Absence of anti-human immunodeficiency virus types 1 and 2 seroconversion after the treatment of hemophilia A or von Willebrand's disease with pasteurized factor VIII concentrate.

Patients with hemophilia A or von Willebrand's disease who are treated with concentrated preparations of human factor VIII made from unscreened pooled plasma are at substantial risk of contracting human immunodeficiency virus (HIV) infection. The purpose of this study was to investigate whether by treating such patients with a pasteurized factor VIII concentrate that had been heated in aqueous solution at 60 degrees C for 10 hours, HIV infection could be avoided. Eleven hemophilia centers in the Federal Republic of Germany and two in Austria identified 155 eligible patients who had been treated exclusively with pasteurized factor VIII concentrate and had not received any other blood products. Between February 1979 and December 1986 they received a total of 15,916,260 IU of pasteurized factor VIII. The United States was the source of 80 percent of the plasma from which the concentrate was made. By September 1988, these 155 patients had been screened for antibody to HIV type 1 (anti-HIV-1) with a total of 657 tests; all were negative. Sixty-seven patients were also tested once for antibody to HIV type 2 (anti-HIV-2); all these tests were negative as well. It appears that pasteurization effectively inactivates HIV, even in plasma that is likely to be highly contaminated with the virus.

Austria↗
PubMed1989

Effects of argon laser radiation on aortic endothelial cells: early membrane changes and proliferative response.

Membrane fluidity, transmembrane signaling responses, and proliferative characteristics of endothelial cells were studied to characterize biochemical and molecular changes after treatment with argon laser energy. Bovine aortic endothelial cells grown in monolayers were irradiated at 50, 100, and 200 J with an argon laser (wavelength, 488 and 514 nm). Proliferation, assayed by [3H]thymidine incorporation, was measured daily for 6 days. An initial lag phase was observed for irradiated cells when compared to nonirradiated controls (P less than 0.03), with eventual recovery by the third day. Membrane fluidity, determined by fluorescence anisotropy, was measured 1 hr after irradiation. A decrease in static rotational motion of 1,6-diphenyl-1,3,5-hexatriene (DPH) was noted in irradiated versus nonirradiated cells indicating a decrease in membrane fluidity (P less than 0.02). Dynamic studies of intracellular calcium and pH flux utilizing fluorescent probes demonstrated a preserved response to mitogenic stimulation. An increase in intracellular Ca2+ with a concomitant alkalinization of the intracellular milieu was observed in irradiated and non-irradiated cells in response to stimulation with endothelial cell growth factor (ECGF). These responses resemble those characterized for other mitogens. Argon laser energy applied to aortic endothelial cells decreases membrane fluidity early after irradiation. These alterations probably cause the initial lag observed in their proliferative response; however, the capacity to respond to exogenous mitogenic stimulation is maintained.

Animals↗
PubMed1986

100 years of DSM-III paranoia. How stable a diagnosis over time?

Modified stricter criteria for DSM-III paranoia were fulfilled by 63 (37%) of 169 Heidelberg probands given a diagnosis of "Case Record Paranoia" (CRP) during a 100-year period (1878-1977). Clinical findings were chiefly interpreted in light of the controversial issues of age, illness duration and type of delusional content pertinent to the formulation of a present-day valid definition for this disorder. With respect to diagnostic consistency over time, 56% of DSM-III paranoia cases with at least one further Heidelberg admission proved to be non-stable, non-consistency being overwhelmingly due to a change in a DSM-III schizophrenic direction.

Adult↗