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Biomedical subjects

L Hansson

Publications and source records attributed to L Hansson.

At least 235 records · Page 13Linked to original sources
PubMed1994

Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase.

The cDNA encoding human stratum corneum chymotryptic enzyme (SCCE); an epidermal serine-proteinase which was recently purified from human stratum corneum, was isolated from a keratinocyte derived library. The obtained nucleotide sequence contained an open reading frame sufficient to encode a preproprotein consisting of 253 amino acid residues. Expression of two mRNA species hybridizing with SCCE cDNA, 1.2 and 2.0 kilobases, respectively, was detected to human skin. These two forms differ with respect to the length of the 3'-untranslated sequence. Analysis of mRNA derived from various human tissues showed that abundant expression of the SCCE gene was restricted to human skin. The cloned cDNA was introduced to a bovine papilloma virus-based expression system and recombinant protein was purified and characterized. The results show that recombinant SCCE is produced with a 22-amino acid residue signal peptide and a propeptide of 7 amino acid residues. Tryptic digestion removed this propeptide and yielded a proteolytically active protein with the same NH2-terminal amino acid sequence as native SCCE. The deduced amino acid sequence contains the conserved active site regions of serine proteinases. The calculated molecular mass of unglycosylated active SCCE was 24.4 kDa. The sequence indicates one tentative N-glycosylation site located near the C terminus. Recombinant SCCE was found to be heterogenous regarding glycosylation in a manner similar to that of the native enzyme.

Abdomen↗
PubMed1994

Expression of human parathyroid hormone in mammalian cells, Escherichia coli and Saccharomyces cerevisiae.

The entire human parathyroid hormone (hPTH) cDNA gene with its natural signal and pro-region is expressed in transfected mouse mammary tumor cells (C127I cells) and Chinese hamster lung cells (DON cells) under control of the murine metallothioneine-1 promoter in a vector in which replication functions are provided by the entire genome of bovine papilloma virus type I (BPV-1). Authentic hPTH is efficiently produced by the non-endocrine cells and secreted to the growth medium without any abberant processing. Immunoblots from SDS-PAGE gels of concentrated growth medium reveal one band corresponding to intact, undegraded hPTH. Purification by reversed-phase HPLC results in a peptide with an amino acid content and N-terminal sequence identical to hPTH. For comparison, hPTH cDNA with deleted prepro-region is also expressed as secretory proteins in Escherichia coli and in Saccharomyces cerevisiae. In E. coli the vector construct is based on the staphylococcal protein A promoter employing protein A signal sequence. In S. cerevisiae a mating factor alpha expression system containing the factor alpha-signal sequence is employed. The results show that intact hPTH is secreted in addition to proteolytically cleaved fragments in both microorganisms. Thus, the signal sequences promote efficient secretion, and correct N-terminal processing of hPTH in both mammalian, bacterial and yeast cells. However, the folding characteristics of hPTH make it susceptible to internal proteolytical cleavage which appears to be species specific in yeast and E. coli.

Amino Acid Sequence↗
PubMed1994

Structure of the human beta-casein encoding gene.

The entire human beta-casein-encoding gene, Bca, was cloned and sequenced. The gene consists of eight exons ranging from 21 to 531 nucleotides (nt) in length and extending over 10,466 nt. Exon-2 contains the translational start, the entire signal sequence and the codons for the two first amino acids of the mature protein. This corresponds to the organization found in other species. The translational stop is localized to exon-7. Exon/intron boundaries are in accordance with the AG/GT rule and conform to suggested consensus sequences. Splice junctions are located between coding triplets. In all other species analyzed, Bca has been found to consist of nine exons; however, within intron-2 of the human gene, a sequence omitted from human mRNA, but corresponding to exon-3 of other known Bca genes, was revealed.

Amino Acid Sequence↗
PubMed1994

Expression and characterization of biologically active human extracellular superoxide dismutase in milk of transgenic mice.

We have targeted the expression of recombinant human extracellular superoxide dismutase, a glycosylated tetrameric metalloprotein, to the mammary gland of transgenic mice. This was achieved by using regulatory elements from either the murine whey acidic protein gene or the ovine beta-lactoglobulin gene to control expression of human extracellular superoxide dismutase cDNA. Whey acidic protein regulatory sequences directed high level mammary gland-specific expression of the recombinant gene and secretion of biologically active extracellular superoxide dismutase into the milk. The produced recombinant protein was fully active, it was in tetrameric form, it showed heparin affinity, and its mass was similar to that of the native enzyme. In addition, the in vivo plasma clearance in a rabbit model was similar to the previously studied native and recombinant forms. To our knowledge, this is the first example of efficient production of a tetrameric, protease-susceptible metalloprotein in milk of transgenic animals. Production at equivalent levels in transgenic farm animals would yield sufficient extracellular superoxide dismutase for therapeutic purposes.

Animals↗
PubMed1994

Intracerebral infusion of (+)-AJ76 and (+)-UH232: effects on dopamine release and metabolism in vivo.

The dopamine D3- and autoreceptor preferring antagonists (+)-AJ76 and (+)-UH232 were administered locally in the striatum and the nucleus accumbens. Their effects on dialysate dopamine and 3,4-di-hydroxyphenylacetic acid (DOPAC) were measured and compared with the effects of raclopride. (+)-AJ76 and (+)-UH232 but not raclopride seem to interact primarily with dopamine receptors in the terminal regions of the A9 and A10 dopaminergic fibers to exert their maximal effect on dopamine release in vivo. Thus, (+)-AJ76 and (+)-UH232 seem to recruit different dopamine receptor populations as compared to raclopride. Though the dopamine receptor antagonist-induced effects on dopamine release seem to be mediated mainly by dopamine receptors in the terminal areas, the effects on DOPAC by the different antagonists seem to be mediated mainly via effects elsewhere, presumably at the somatodendritic autoreceptors. Thus, it is suggested that the regulation of extracellular dopamine and DOPAC after treatment with dopamine receptor antagonists are subjected to different control mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1994

Separation of active and inactive forms of recombinant human plasminogen activator inhibitor type 1 (PAI-1) expressed in Chinese hamster ovary cells: comparison with native human PAI-1.

Human plasminogen activator inhibitor type 1, PAI-1, was expressed in Chinese hamster ovary cells. A production level of 10-15 mg latent PAI-1 per liter of media was achieved after methotrexate amplification. Latent recombinant PAI-1 was purified by two chromatographic steps, cation exchange chromatography on CM-Sepharose and affinity chromatography on heparin-Sepharose. The obtained latent PAI-1 was approximately 90-95% pure showing one homogenous peak upon size-exclusion chromatography. However, four different isoforms due to different degrees of sialylation could be seen upon isoelectric focusing. Purified latent PAI-1 was activated by incubation in 6 M guanidine-HCl. By this method, 40-60% of PAI-1 was converted to an active form after removing the denaturant. The active fraction of PAI-1 was separated from inactive material by size exclusion chromatography on Superdex 200. Active PAI-1 migrated as expected for a 43-kDa large protein, while inactive PAI-1 migrated as larger protein complexes, suggesting that the remaining inactive PAI-1 was in the form of aggregates. This method for the separation of active and inactive PAI-1 could also be used for activated native PAI-1 prepared from human endothelial cells. Active recombinant PAI-1 was remarkably stable at pH 5.5, both when stored on ice and when stored at room temperature.

Amino Acids↗
PubMed1994

The course of psychiatric illness in primary care patients. A 1-year follow-up.

The aim of the study was to investigate the course of psychiatric illness in primary care patients. A 12-month follow-up study was conducted using a subsample of 93 patients, assessed by interviewing with the aid of the Present State Examination (PSE), from an original cohort of 388 primary care patients in a Swedish health district. The relationships of the course of illness to psychosocial stress, perceived health, utilization of care and health insurance, and patient satisfaction with primary health care services were investigated. The results showed that at index contact, 32.1% of the follow-up sample were psychiatric cases in need of treatment according to the screening procedure with the Hopkins Symptom Check List (HSCL-25). The continuing cases constituted 19% of the total follow-up sample, remitting cases, 13.1%, new cases, 4.8% and non-cases, 63.1%. Continuing cases had a significantly higher utilization of ambulant care during follow-up. They also had 3 times more days of sick-leave. Poor perceived health at index contact, measured using the Nottingham Health Profile (NHP), predicted that the patient became a continuing case during follow-up. Continuing cases, to a greater extent, showed psychosocial stress concerning unemployment, private economy and loneliness/social isolation. Continuing cases also showed a lower satisfaction with primary health care services in all areas measured.

Adolescent↗
PubMed1994

Screening for psychiatric illness in primary care. A cross-sectional study in a Swedish health district.

A sample of 388 primary care patients in a Swedish health district were screened for psychiatric illness using the Hopkins Symptom Check List HSCL-25. General practitioner (GP) ratings of psychiatric illness and patient ratings of psychosocial problems were also included. Data concerning the patients' utilization of care and health insurance were recorded. According to the HSCL-25, 30.2% of the patients were probable psychiatric cases and 19.2% were psychiatric cases in need of treatment. According to GPs' independent ratings, 12.3% of the patients suffered from psychiatric illness requiring treatment. Psychiatric cases according to HSCL-25 were more often women, divorced, unemployed and living alone. During the year preceding index contact, psychiatric cases showed a higher utilization of primary care, as well as other somatic care. They also had more sick leave. Psychiatric cases perceived higher levels of psychosocial problems in areas of unemployment, work situation, private economy, child care and social isolation. The results of the study point to the interaction of psychological impairment, environmental stress and lack of social support in producing psychiatric illness.

Adolescent↗
PubMed1994

Predictors of blood pressure and left ventricular mass in the young: the Hypertension in Pregnancy Offspring Study.

The present study evaluates potential predictors for the future blood pressure and left ventricular mass in children. Fifty-two children were studied at mean age 12.6 +/- 1.5 years and reexamined after 5.6 years. Thirty-six children were born to mothers who had hypertension during pregnancy and 16 children were born after normotensive pregnancies by mothers who remained normotensive at follow-up. Blood pressure was measured at rest and during physical exercise. Left ventricular mass was calculated from M-mode echocardiography, and erythrocyte sodium and potassium concentrations were determined. A stepwise multiple linear regression analysis was used to predict subsequent blood pressure and left ventricular mass. Final systolic blood pressure was best explained by initial systolic blood pressure, erythrocyte potassium concentration, gender, and erythrocyte sodium concentration. Final diastolic blood pressure was best explained by erythrocyte potassium concentration. Gender and initial left ventricular mass were predictors of left ventricular mass at follow-up. This prospective study corroborates previous findings that blood pressure measured in children predicts their future blood pressure. Furthermore, an independent inverse relationship between childhood erythrocyte potassium concentration and adolescent blood pressure is demonstrated. Male gender and an early increased left ventricular mass are independent predictors of an increased left ventricular mass in adolescents.

Blood Pressure↗
PubMed1994

Treatment of hypertension in the elderly.

In the span of little more than half a year, three major, prospective, placebo-controlled intervention trials against hypertension in the elderly were published, i.e., the Systolic Hypertension in the Elderly Program (SHEP) from the United States in 1991, the Swedish Trial in Old Patients with Hypertension (STOP Hypertension), also in 1991, and the Medical Research Council (MRC) Study in older adults from the United Kingdom in 1992. These trials compared active antihypertensive treatment in elderly patients to placebo, and all found significant benefits from active treatment, particularly against stroke. In the SHEP trial, coronary heart morbidity was also positively affected, and in the STOP Hypertension study total mortality was reduced significantly. In all the three studies, active treatment consisted of diuretics and/or beta-blockers, usually given in combination. It is conceivable that novel classes of compounds, e.g., the calcium antagonists, might have shown even better results in the prevention of cardiovascular morbidity and mortality, in view of their neutral metabolic profile and possible antiatherosclerotic effect. Studies are currently in progress to test this possibility, e.g., the STOP-Hypertension-2 study. While the results of such ongoing trials are awaited, it is worth noting that treatment with calcium antagonists in the elderly, e.g., with lacidipine, in several studies has been shown to be remarkably effective and well tolerated. This raises the possibility that results of antihypertensive treatment in the elderly could become even better than those already obtained in the SHEP, STOP-Hypertension, and MRC trials.

Antihypertensive Agents↗
PubMed1994

Relation of maternal blood pressure during pregnancy to birth weight and blood pressure in children. The Hypertension in Pregnancy Offspring Study.

OBJECTIVE: To evaluate the importance of perinatal factors, e.g. low birth weight, reduced gestational period and elevated maternal blood pressure during pregnancy, as well as high maternal blood pressure at follow-up 7-12 years after pregnancy, on blood pressure in children born after normotensive and hypertensive pregnancies. DESIGN: Follow-up study in children from hypertensive pregnancies and a control group of children born after normotensive pregnancies. SETTING: University Hospital, Göteborg, Sweden. SUBJECTS: Thirty-six children born after hypertensive pregnancies and a control group of 17 children born after normotensive pregnancies were studied at a mean age of 12.5 years. MAIN OUTCOME MEASURE: Blood pressure. RESULTS: Systolic blood pressure was higher in children born after hypertensive pregnancies. They also had lower birth weight and a shorter gestational period. There was a negative correlation between the highest recorded maternal blood pressure during pregnancy and birth weight of the child and a positive correlation between maternal blood pressure and blood pressure in their offspring. No correlation was found between birth weight and blood pressure in these children. CONCLUSIONS: Children born after hypertensive pregnancies have higher blood pressure compared to children born after normotensive pregnancies. There is a positive relationship between childhood blood pressure and maternal blood pressure during pregnancy.

Adolescent↗
PubMed1994

A 5-year prospective, observational study of the withdrawal of antihypertensive treatment in elderly people.

OBJECTIVES: To observe blood pressure, cardiovascular events, and total mortality after withdrawing antihypertensive treatment for elderly patients. DESIGN: Multicentre observational study. SETTING: Sweden. A 5-year follow-up of 333 elderly hypertensive patients, aged 70-84 years (mean age 75.2 +/- SD 3.8 years, 68% females). In all, 74 out of the 333 patients (22%) died during the study period. METHOD: After withdrawal of the antihypertensive therapy, all patients started in the untreated state and during the 5-year follow-up they could then either remain in the untreated state, or be reverted to blood-pressure-lowering drug treatment because of hypertension or other diseases, e.g. angina pectoris, oedema, congestive heart failure, etc. RESULTS: The probability of remaining without treatment for 5 years was estimated to be 20%. During the state of no treatment the patients had a lower total mortality risk than that of the general Swedish population, matched for age and sex. They also had a lower risk of cardiovascular events than those in the treated states. Markers indicating a successful withdrawal were monotherapy in low doses and relatively low blood pressure before withdrawal. CONCLUSION: These results suggest that with frequent check-ups, withdrawal of antihypertensive therapy in the elderly can be tried without increased risk of cardiovascular events.

Aged↗
PubMed1994

Patient satisfaction with inpatient psychiatric care. The influence of personality traits, diagnosis and perceived coercion.

The aim of the study was to investigate the influence of personality traits, diagnosis and perceived coercion on patient satisfaction with inpatient psychiatric care. The study was performed as a cross-sectional study on 7 inpatient wards in southern Sweden. A cohort of 50 psychiatric inpatients evaluated satisfaction with care and also made ratings on a personality questionnaire. Patients with a higher level of the trait aggressive nonconformity were significantly less satisfied with the ward's physical and psychosocial environment, the treatment design and the treatment program. The phenomenon of acquiescence was not related to the reported level of satisfaction. Analyses of patient satisfaction according to diagnostic groups showed that patients with affective disorders had significantly better satisfaction than patients with a diagnosis of schizophrenia. Patients who perceived that they were involuntarily admitted were measured as being significantly less satisfied with the care in all areas. It is concluded that, to attain a higher specificity in analyses of variation in patient satisfaction, focus may be put on situational and setting factors of the care delivered along with specific patient characteristics. Risk groups, which require great attention in the development of quality assessment and quality assurance policies, are patients with schizophrenia and patients who perceive coercion in connection with inpatient psychiatric treatment.

Adolescent↗
PubMed1994

Effects of inhaled lignocaine and adrenaline on capsaicin-induced cough in humans.

BACKGROUND: The hypothesis that adrenaline can augment and/or prolong the antitussive effect of nebulised lignocaine was examined. METHODS: The effect of inhaled lignocaine alone (20 mg) and in combination with adrenaline (400 micrograms) was studied on capsaicin-induced cough in 10 healthy subjects. RESULTS: Cough was significantly reduced between five and 25 minutes by lignocaine. Adrenaline alone had no inhibitory effect and it neither augmented nor prolonged the antitussive effect of lignocaine. The subjective anaesthesia by lignocaine was short lasting (less than 15 minutes) and not altered by adrenaline, suggesting different sensory mechanisms for anaesthesia and cough suppression. Plasma concentrations of lignocaine were low (< 30 ng/ml), not altered by adrenaline, and did not correlate with the local anaesthetic or the antitussive effect. CONCLUSIONS: Lignocaine acts locally in the oropharynx and airways and adrenaline does not alter the effect or absorption of nebulised lignocaine on the human respiratory mucosa.

Administration, Inhalation↗
PubMed1994

Inhaled nicotine in humans: effect on the respiratory and cardiovascular systems.

Inhalation of nicotine (0-64 mg/ml) and capsaicin (2 x 10(-6)-2.5 x 10(-4) M) in 24 healthy nonsmoking subjects produced a concentration-dependent cough response. Two subjects coughed to capsaicin but not to nicotine. The mean (95% confidence interval) nicotine concentrations causing two and five coughs were 5.5 (3.5-8.7) and 15.8 (10.0-25.1) mg/ml, respectively, and were reproducible over 3 different days. Capsaicin inhalation did not alter the response to nicotine and vice versa. Both agents increased respiratory resistance, but the response was more rapid to capsaicin. Inhalation of nicotine (0-8 mg/ml) over 5 min caused increases in heart rate and blood pressure and a decrease in skin temperature. Inhaled ipratropium bromide (0.50 mg) had an antitussive effect and also inhibited the nicotine-induced bronchoconstriction, indicating a vagally mediated effect. Sodium cromoglycate (0.20 mg) did not affect cough or airway resistance changes caused by nicotine. This study shows that inhaled nicotine produces a concentration-dependent cough and airway obstruction in healthy subjects, probably because of stimulation of afferent nerve endings in the bronchial mucosa and mediated through parasympathetic cholinergic pathways. Respiratory reflexes evoked by nicotine are similar to those produced by capsaicin, but it is unclear whether these reflexes are mediated by the same type of sensory nerves.

Administration, Inhalation↗
PubMed1994

Psychosocial outcome 5-8 years after severe traumatic brain lesions and the impact of rehabilitation services.

This study addresses three questions. First, what is the long-term psychosocial outcome for severely head-injured patients? Second, is an increased survival rate associated with an increase in the number of patients with a poor quality of life? Third, do rehabilitation services affect the final outcome? The long-term outcome was assessed by means of questionnaires for self-ratings, interviews with patients and relatives and neurophysical examinations. One hundred and six patients initially judged as good recovery/moderate disability (GR/MD) 6 months post-injury participated in the study. Forty to 50% of these patients showed co-ordination disturbances; more than 20% had speech disorders and cranial nerve deficits. Twenty-eight per cent had psychiatric symptom scores on the Hopkins Symptom Checklist (HSCL) indicating need of treatment. Social function according to the Social Adjustment Scale--Self-Report (SAS--SR) showed that 40% had problems concerning interpersonal relations and 20-30% had problems within the field of leisure activities, but few problems were reported on work activities and economy. The Comprehensive Psychopathological Rating Scale (CPRS) revealed that hostile feelings, failing memory and fatiguability were common symptoms and were reported by relatives in 71%, 52% and 48%, respectively, but the mean distress levels were moderate. A correlation was seen between quality of life reported by relatives and the degree of mental and social disability according to the Bond Outcome Scale, but the correlation to neurophysical handicap was rather weak. The majority of patients were able to return to a productive social life. The proportion of patients with a poor long-term outcome did not increase after introduction of an aggressive management protocol for head injuries. Data indicated that improvements in facilities for rehabilitation may positively affect psychosocial adjustment.

Adolescent↗
PubMed1994

The Hypertension Optimal Treatment (HOT) Study--patient characteristics: randomization, risk profiles, and early blood pressure results.

The Hypertension Optimal Treatment (HOT) Study is a prospective, randomized, multicenter trial being conducted in 26 countries. Its main aim is to evaluate the relationship between three levels of target diastolic blood pressure (< or = 90, < or = 85 or < or = 80 mmHg) and cardiovascular morbidity and mortality in hypertensive patients. In addition, the study will examine the effects on morbidity and mortality of a low dose, 75 mg daily, of acetylsalicylic acid (ASA, aspirin) or placebo. In the HOT Study, basic antihypertensive treatment is initiated with the calcium antagonist felodipine at a dose of 5 mg daily. If target blood pressure is not reached, additional antihypertensive therapy with either an angiotensin converting enzyme (ACE) inhibitor or a beta-adrenoceptor blocking agent is given. Further dosage adjustments are made in accordance with a set protocol. As a fifth and final step, a diuretic may be added. Inclusion of patients was stopped on April 30, 1994. At that time 19,196 patients had been randomized. There were 9,055 (47%) women and 10,141 (53%) men with an average age of 61.5 +/- 7.5 (SD) years. At enrollment, 52% of patients were receiving antihypertensive treatment. These patients entered a wash-out period of at least 2 weeks before randomization. The average randomization blood pressure in untreated patients was 169 +/- 14/106 +/- 3 mmHg and in the treated patients 170 +/- 14/105 +/- 3 mmHg. On August 15, 1994, blood pressure data were available for 14,710 and 10,275 patients, who had completed 3 and 6 months treatment, respectively. The average reduction in diastolic blood pressure was 22 mmHg after 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗