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L Kühn

Publications and source records attributed to L Kühn.

At least 19 recordsLinked to original sources
PubMed2000

Mechanisms of differential transferrin receptor expression in normal hematopoiesis.

We have investigated the expression of transferrin receptor (TfR) iron regulatory protein-1 (IRP-1) and iron regulatory protein-2 (IRP-2) in liquid suspension culture of purified hematopoietic progenitor cells (HPCs) induced by a growth factor stimulus to proliferation and unilineage differentiation/maturation through the erythroid, granulocytic, monocytic and megakaryocytic lineages. In initial HPC differentiation, TfR expression is induced in both erythroid and granulopoietic cultures. In late HPC differentiation (i.e. starting from day 5 of culture) and then differentiated precursor maturation, the TfR gene is highly expressed in the erythroid lineage, whereas it is sharply downmodulated in the granulopoietic, monocytopoietic and megakaryocytic series. The elevated TfR expression in erythroid cells is: (a) mediated through a high rate of TfR gene transcription; (b) modulated by intracellular iron levels; (c) mediated by TfR mRNA stabilization through the iron regulatory protein (IRP), in that IRP-1 activity is high in erythroid lineage as compared to the levels observed in other hemopoietic lineages; and (d) dependent on exogenous erythropoietin (Epo) (this is indicated by the marked TfR and IRP-1/IRP-2 downmodulation after Epo starvation). Interestingly, analysis of IRP-1 and IRP-2 expression during hemopoietic differentiation showed that: (a) IRP-1 expression was maintained during all steps of erythroid differentiation, while it was lost in the other hemopoietic lineages; (b) IRP-2 expression was observed during all stages of hemopoietic differentiation in all four lineages. However, IRP-1 and IRP-2 expression and activity are induced when monocytes, which express only low levels of IRP-1 and IRP-2, are induced to maturation to macrophages. These studies indicate that: (a) in normal erythropoiesis, the hyperexpression of TfR, starting from early erythroid HPC differentiation, is Epo-dependent and mediated via transcriptional and post-transcriptional mechanisms; (b) in the granulopoietic, monocytopoietic and megakaryocytic pathways, the TfR is first induced and then downmodulated (the latter phenomenon is mediated via transcriptional suppression of the TfR gene and IRP inactivation).

Adult↗
PubMed1999

Amino acid transport of y+L-type by heterodimers of 4F2hc/CD98 and members of the glycoprotein-associated amino acid transporter family.

Amino acid transport across cellular membranes is mediated by multiple transporters with overlapping specificities. We recently have identified the vertebrate proteins which mediate Na+-independent exchange of large neutral amino acids corresponding to transport system L. This transporter consists of a novel amino acid permease-related protein (LAT1 or AmAT-L-lc) which for surface expression and function requires formation of disulfide-linked heterodimers with the glycosylated heavy chain of the h4F2/CD98 surface antigen. We show that h4F2hc also associates with other mammalian light chains, e.g. y+LAT1 from mouse and human which are approximately 48% identical with LAT1 and thus belong to the same family of glycoprotein-associated amino acid transporters. The novel heterodimers form exchangers which mediate the cellular efflux of cationic amino acids and the Na+-dependent uptake of large neutral amino acids. These transport characteristics and kinetic and pharmacological fingerprints identify them as y+L-type transport systems. The mRNA encoding my+LAT1 is detectable in most adult tissues and expressed at high levels in kidney cortex and intestine. This suggests that the y+LAT1-4F2hc heterodimer, besides participating in amino acid uptake/secretion in many cell types, is the basolateral amino acid exchanger involved in transepithelial reabsorption of cationic amino acids; hence, its defect might be the cause of the human genetic disease lysinuric protein intolerance.

Amino Acid Sequence↗
PubMed1992

Post-transcriptional regulation of transferrin receptor mRNA by IFN gamma.

IFN gamma inhibits the rise in transferrin receptor mRNA level which is normally observed when stationary WISH cells are stimulated to proliferate. This effect is not attributable to a change in the transcription rate of the transferrin receptor gene or in the cytoplasmic stability of the mRNA. The IFN gamma-induced reduction of the transferrin receptor mRNA content is already present at the nuclear level to an extent comparable to that observed in whole cells. Thus, IFN gamma does not impair the passage of this mRNA from the nuclear to the cytoplasmic compartment but probably interferes with a nuclear post-transcriptional event during the processing of the immature transferrin receptor mRNA. Two different levels of regulation of transferrin receptor mRNA have been previously reported. Iron modulates the cytoplasmic stability of this mRNA through the binding of a specific cytoplasmic factor, whereas cell growth variation influences the transcription of this gene. Our results suggest the existence of another mechanism of regulation for transferrin receptor gene expression not so far considered. Furthermore, the distinction between the mechanism of regulation exerted by IFN gamma and that exerted by cell proliferation on transferrin receptor gene expression suggests that, in WISH cells, the IFN-induced transferrin receptor decay is not a consequence of cell growth arrest but rather one of the causes of the antiproliferative effect of IFN through iron deprivation.

Blotting, Northern↗
PubMed1992

[Intuitive prognostic assessment in rehabilitation of long-term psychiatric patients].

The significance of intuitive prognostic assessments by the nursing staff and the examining female doctor is studied with regard to the course and results of "late rehabilitation" of 30 psychiatric patients who had been hospitalised for many years. Using standardised assessment criteria and catamnestic data on readmission as inpatients (covering a period of 20 months) patients were compared who had been discharged from the psychiatric hospital, transferred to long-term residential quarters, and assessed before discharge as likely or unlikely to be readmitted to the hospital. The group of patients who had been given an unfavourable prognosis--most of them women--proved in course of time to be readmitted as inpatients more often and to be significantly more disturbed than the patients who had been discharged with a more favourable prognosis. These results are discussed with regard to sociopolitical and medical care aspects and to approaches for further research in this direction.

Activities of Daily Living↗
PubMed1991

Differential regulation of iron regulatory element-binding protein(s) in cell extracts of activated lymphocytes versus monocytes-macrophages.

The intracellular iron level exerts a negative feedback on transferrin receptor (TfR) expression in cells requiring iron for their proliferation, in contrast to the positive feedback observed in monocytes-macrophages. It has been suggested recently that modulation of TfR and ferritin synthesis by iron is mediated through a cytoplasmic protein(s) (iron regulatory element-binding protein(s) (IRE-BP)), which interacts with ferritin and TfR mRNA at the level of hairpin structures (IRE), thus leading to inhibition of transferrin mRNA degradation and repression of ferritin mRNA translation. In the present study we have evaluated in parallel the level of TfR expression, ferritin, and IRE-BP in cultures of: (i) circulating human lymphocytes stimulated to proliferate by phytohemagglutinin (PHA) and (ii) circulating human monocytes maturing in vitro to macrophages. The cells were grown in either standard or iron-supplemented culture. TfR and ferritin expression was evaluated at both the protein and mRNA level. IRE-BP activity was measured by gel retardation assay in the absence or presence of beta-mercaptoethanol (spontaneous or total IRE-BP activity, respectively). Spontaneous IRE-BP activity, already present at low level in quiescent T lymphocytes, shows a gradual and marked increase in PHA-stimulated T cells from day 1 of culture onward. This increase is directly and strictly correlated with the initiation and gradual rise of TfR expression, which is in turn associated with a decrease of ferritin content. Both the rise of TfR and spontaneous IRE-BP activity are completely inhibited in iron-supplemented T cell cultures. In contrast, the total IRE-BP level is similar in both quiescent and PHA-stimulated lymphocytes, grown in cultures supplemented or not with iron salts. Monocytes maturing in vitro to macrophages show a sharp increase of spontaneous and, to a lesser extent, total IRE-BP; the addition of iron moderately stimulates the spontaneous IRE-BP activity but not the total one. Here again, the rise of spontaneous IRE-BP from very low to high activity is strictly related to the parallel increase of TfR expression and, suprisingly, also with a very pronounced rise of ferritin expression observed at both the mRNA and protein level. It is noteworthy the effect of beta-mercaptoethanol is cell specific, i.e. the ratio of total versus spontaneous IRE-BP activity is different in activated lymphocytes and maturing monocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1990

Gender and the course of schizophrenia: differences in treated outcomes.

A survey of the literature suggests that women tend to exhibit a more favorable course of schizophrenia than men. This seems to be true for a range of outcome measures, such as hospital treatment, psychopathology, and social adaptation. Due to methodological limitations, however, the empirical evidence for gender differences in outcome is not wholly consistent. In 1983, a study of first-admitted patients with DSM-III diagnoses of schizophrenia or schizophreniform disorder (n = 278) from the Greater Hannover area in the Federal Republic of Germany followed patients for an average of 3 years. The present study has followed these patients for an average of 8 years. When confounding factors (e.g., age and marital status) were controlled for, schizophrenic women showed a better course of hospital treatment, experienced a shorter length of hospital stay, and survived longer in the community after their first hospital admission. Only the number of hospitalizations did not differ significantly between the sexes in the present study in contrast to the original study.

Adult↗
PubMed1989

Polyclonal rearrangements of the T-cell receptor beta-chain in fatal angioimmunoblastic lymphadenopathy.

Genomic rearrangement of germline T-cell antigen receptor (TcR) and immunoglobulin (Ig) genes was studied by Southern blot analysis in seven patients with angioimmunoblastic lymphadenopathy (AILD). In three cases clinically suspected of transformation into malignant lymphoma, hybridization with the TcR beta probe showed markedly dimished intensity in the 11.5 kb germline band after Eco RI digestion and normal germline configuration after Hind III and Bam HI digestion, indicating polyclonal T cell rearrangements. A clonal rearrangement of the TcR beta gene was detected in only one case at initial biopsy. No monoclonal rearrangement of Ig genes was observed. These data show that in some cases of AILD disease progression is indicated by polyclonal TcR rearrangements and not by outgrowth of a malignant clone, supporting the concept of AILD as an immunoregulatory disorder.

Blotting, Southern↗
PubMed1988

Gender differences in age at onset of schizophrenia. An overview.

We present the results of a review of the literature concerning gender differences in age at the onset of schizophrenia. In view of the very consistent finding that the first admission to hospital for schizophrenia occurs on average earlier in men than in women we examined the question whether this is due to the fact that the psychosis manifests itself earlier in men or that the period between first manifestation and admission to hospital is shorter than in women. By means of a metaanalytic approach we then looked for evidence for the existence of local or temporal variations in the degree of gender difference. Lastly, we dealt with the question whether gender differences in age of onset can be observed in other functional psychoses.

Age Factors↗
PubMed1987

Birthday and date of death.

The relation between birthday and date of death has so far been studied from two different perspectives: birthdays were either conceived of as emotionally invested deadlines motivating people to ward off their death which causes a 'dip' in death rates before their birthday, or they were considered as stressful events leading to an increase of mortality on or after their birthday. Using a collection of biographies of famous people from the whole world and another of well-known Swiss citizens we tested hypotheses derived from these assumptions. Neither the 'death-dip' hypotheses nor the 'birthday stress' hypothesis was supported by our results.

Anniversaries and Special Events↗
PubMed1985

Antibodies recognizing different domains of the polymeric immunoglobulin receptor.

The receptor responsible for the transepithelial transport of IgA dimer antibodies is a transmembrane glycoprotein known as membrane secretory component (SCm). During transport, the membrane anchoring domain is cleaved and the ectoplasmic domain of the receptor (SCs) remains tightly bound to the IgA dimer in exosecretions. We have produced monoclonal antibodies with distinct specificities against both cytoplasmic and ectoplasmic epitopes of rabbit SCm. One antibody (anti-SC303) reacted both with SCm and free SCs but not with SCs bound to IgA dimer (SIgA). Therefore, it recognized an epitope close to the IgA dimer binding site. The other monoclonal antibody (anti-SC166), which was unable to react with SCs, bound to the 15-kDa cytoplasmic extension of the membrane-spanning domain of the receptor. A polyclonal antibody (GaR-SC), raised in a goat against rabbit milk SCs, reacted with a subpopulation of SCs not recognized by the anti-SC303 monoclonal antibody and in addition also reacted with covalently bound sIgA. The three antibodies cross-reacted with rat SCm. We demonstrate the ability of the anti-SC166 monoclonal antibody to immunoadsorb subcellular organelles as a result of the cytoplasmic orientation of its epitope. Our data indicate that there are functional differences between the high- and low-molecular-weight families of SC in terms of IgA dimer binding.

Animals↗
PubMed1985

Regional localization of the human transferrin receptor gene to 3q26.2----qter.

Transport of iron across the cell membrane is mediated by the iron-binding serum protein, transferrin, and its cell-surface receptor. Transferrin receptor is required for cell proliferation and may play a functional role in the pathogenesis of iron-storage disorders and some neoplasias. To better understand the possible involvement of transferrin receptor in such disorders, we have determined the chromosomal locus of the receptor gene by in situ hybridization. The human transferrin receptor gene was thus mapped to 3q26.2----qter, a region of chromosome 3 that appears to be involved in metal transport and that is subject to nonrandom structural rearrangements associated with neoplasia.

Chromosome Mapping↗
PubMed1983

Somatic cell genetics and flow cytometry.

Human genes coding cell surface molecules can be introduced into mouse host cells using a variety of somatic cell genetic techniques. Because these human gene products can be detected using indirect immunofluorescence on viable cells, the genes themselves can be monitored and manipulated using flow cytometry and sorting. In this paper, we review ways that we have used cell sorting to develop a somatic cell genetic analysis of the human cell surface.

Animals↗
PubMed1979

Binding and degradation of insulin by plasma membranes from bovine liver isolated by a large scale preparation.

With the large-scale preparation described, as much as 1 kg of bovine liver can be processed, giving a yield of more than 1 g plasma membrane protein. From analytical and morphological criteria the plasma membrane fraction isolated mainly derives from bile-canalicular and contiguous areas of the hepatocytes. The insulin binding activity is quite similar to insulin receptors in other cell systems and membrane preparations. Insulin-degrading activity is very low in the isolated plasma fraction. Most of degrading activity is located in a microsomal membrane fraction. Nevertheless the Km and the pH dependence of the insulin-degrading activity in both fractions are nearly identical. From these studies we conclude that binding and degradation of insulin are two independent processes located on different cell organelles.

Animals↗