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- Vumma, Ravi
(författare)
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Functional Characterization of Tyrosine Transporters in fibroblast from Healthy Controls and Schizophrenic Patients
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cultured human fibroblasts offer an advantageous system to investigate the amino acid transport properties without confounding the affects of disease state and its treatment in many systemic psychiatric disorders. In previous studies, fibroblast cells have been used to investigate the tyrosine transport across plasma membranes in patients with schizophrenia and autism with out characterizing the particular amino acid transporters.The importance of the major tyrosine transporters (system-L and system-A) was investigated in this study. Systemic functional characterization of tyrosine transport in fibroblasts from healthy controls and patients with schizophrenia, with respect to the system-L isoforms (LAT1, LAT2, LAT3, and LAT4) was performed.Ten (n=10) fibroblast cell lines from healthy controls and ten (n=10) from patients with schizophrenia were included in this study. Transport and uptake of [14-C] L-tyrosine in fibroblasts was measured using the cluster tray method in the absence and presence of different specific inhibitors. The maximal transport capacity, Vmax and the affinity constant of the tyrosine-binding site, Km, of LAT1 isoform were determined.The results of this study showed that tyrosine transport in fibroblasts is facilitated mainly by the system-L and LAT1 isoform is involved in 90% of total tyrosine uptake. LAT2 isoform seems to be functionally weak in uptake of tyrosine, as not more than 3% could be contributed by it. LAT3 and LAT4 contributed around 7%. System-A (ATA2 isoform) contributed around 10%. Alanine consequently inhibited the tyrosine transport by up to 60%. Tyrosine uptake and kinetics did not differ between patients and controls at the LAT1 isoform. Moreover, the affinity of LAT1 isoform for tyrosine was higher when compared to system-L. LAT1 is also involved in around 51% of uptake of alanine.In conclusion, the present thesis, confirms the presence of system-L with its isoform LAT1 as a main transporter of tyrosine in human fibroblast cells. The competition between tyrosine and alanine to get transported is shown to probably exist mainly at LAT1 isoform. Aberrant tyrosine transport observed in previous studies in patients with schizophrenia is probably not linked to the LAT1 isoform. This study gave further importance and established fibroblast cells as a suitable experimental model for studying amino acid transport properties in humans.Key words: Fibroblasts, Tyrosine and alanine transport, System-L, LAT1, LAT2, LAT3, LAT4, Schizophrenia, Precursor of Dopamine.
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| 2. |
- Berggren, Elisabeth
(författare)
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Identity construction and memory after Subarachnoid Haemorrhage : Patients' accounts and relatives' and patients' statements in relation to memory tests
- 2010
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: A Subarachnoid haemorrhage (SAH) is a complex pathophysiological event and most patients have, before the onset, felt completely well. Being stricken by a SAH is a dramatic event, often followed by unconsciousness and memory problems. This may influence the adjustment to daily life. Supporting patients and relatives in nursing care therefore requires knowledge concerning patients' experience of the onset of the SAH event, and knowledge concerning patients' memory after a SAH.Aim: The general aim of this thesis was to study patients' experiences and reconstruction of the onset of, and events surrounding, a SAH and to study patients' and relatives' experience of patients' memory ability, in a long-term perspective.Specific aims:(I) The aim of this study was to analyse people's accounts of SAH, and to describe how they initiate and create meaning for the onset and events surrounding the SAH. The specific questions were : (i) What is highlighted in the accounts of SAH? (II) How is the illness reconstructed? (iii) How is meaning created through communicative interaction with others about SAH?(II) The aim was to describe memory after a SAH from the perspective of relatives and patients in two cohorts. In this study, the researchers also aimed to evaluate the application of relatives' statements as a tool in nursing care and rehabilitation, in order to support the patients. This was achieved by comparing: (i) Relatives' statements with patients' statements and (ii) Relatives' and patients' statements with the patients' memory test results.Methods: Both an inductive and a deductive approach were used. Nine open interviews were carried out in home settings, 1 year and 7 months (ranging 14-24 months) after the patients' onset and discourse analysis was used to interpret the data (I). Eleven relatives and 11 patients, 11 years and 15 relatives and 15 patients, 6 years after the onset participated in two studies. Interview questions and memory tests were used to collect data. Fischer's exact test was used for the statistical analysis (II).Findings:Patient with experience of a SAH were able to judge their own memory for what happened when they became ill. Both conscious irrational and rational actions were expressed in relation to experienced sensations. Critical events related to SAH were "existential insights" and "time as waiting and time as structuring meaning". The reconstruction of the illness event may be interpreted as an identity ceating process. The process of meaning-making is both a matter of understanding SAH as a pathological event, and a social and communicative matter, where the SAH is constructed into a meaningful life history, in order to make life complete (I). Memory problems were common according to relatives' and patients' statements and from memory test results. There was correspondence between relatives' and patients' statements regarding the patients' memory in general and long-term memory. Patients judged their own memory ability better than relatives, compared with results on memory tests. Both relatives and patients underestimated older patients' memory ability and underrated younger patients' memory problems, when compared with results on memory tests. Relatives stated that some patients had meta-memory problems (II). The episodic memory seemed to be well preserved, both concerning the onset (I) and in the long-term perspective (II).Conclusions: The reconstruction of the illness is a tool in nursing for understanding the patient's self-positioning and identity-construction. (I) Relatives' and patients' statements regarding patients' memory can also be used as tools in nursing care. However, the results showed: meta-memory problems (relatives' statements); that patients' judged their own memory ability better than relatives in comparison with results on memory tests. Consequently, memory tests and formalized dialogues, between the patient, the relative and a professional are required in order to prevent complications in the patient's mutual family relationships. However, professionals must assume that patients can judge their own memory (II). Dialogues between the patient, the relative and a professional, with focus on how to manage daily life in patients' home context, due to the patient's experience of the onset of the SAH and possible memory problems after the SAH, will probably improve the mutual family relationship in a positive way (I,II).
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| 5. |
- Jonsson, Pysse, 1976-
(författare)
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10-year Outcome of Childhood Epilepsy in Well-functioning Children and Adolescents
- 2014
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Epilepsy is one of the most common neurologic disorders in children and young adults. The prognosis depends on various conditions but the long-term prognosis regarding seizure freedom is positive in the majority of the children. Individuals with childhood-onset epilepsy are reported to have more problems in social functioning and psychological well-being compared with healthy control. The aim of this study was to investigate 10-year outcome of medical, psychological and social outcome in well-functioning individuals with childhood-onset epilepsy. Methods: Forty-five individuals and their parents completed a questionnaire regarding family history of epilepsy, febrile seizures, primary, mental retardation and behaviour disorders; and patients history of actual seizure situation, antiepileptic drug medication, febrile seizures, behaviour disorders, primary headaches, and schooling (Study I). Two families denied participation. Out of the remaining 45 families, 31 filled in a questionnaire - Achenbach System of Empirically Based Assessment (ASEBA) - assessing competence, adaptive functioning and behavioural/emotional problems (Study II). Results: The overall remission was 75.6%. Of the 11 with active epilepsy five had cryptogenic/ unknown or structural/symptomatic focal epilepsy; one had idiopathic photosensitive occipital epilepsy, one each with the diagnoses childhood absence epilepsy and juvenile absence epilepsy, and three with other idiopathic generalized epilepsies. The family history of epilepsy was 44% and of febrile seizures 17.7%. A coincidence of focal and generalized epilepsy phenotypes was found in some families. Behavioral, emotional and school problems were found in 29%. Those with active epilepsy had significantly more attention problems and somatic complaints than those in remission. Two individuals presented several problems in the clinical range. Conclusion: Longitudinal studies are of importance in epilepsy epidemiology. Early intervention in children and adolescents with epilepsy is of importance as knowledge about the disorder and eventual additional co-morbidities decreases the risk of depression, social anxiety and low self-esteem in adulthood.
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