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Biomedical subjects

B Löfgren

Publications and source records attributed to B Löfgren.

At least 19 recordsLinked to original sources
PubMed1999

PKCepsilon, via its regulatory domain and independently of its catalytic domain, induces neurite-like processes in neuroblastoma cells.

To investigate the role of protein kinase C (PKC) isoforms in regulation of neurite outgrowth, PKCalpha, betaII, delta, and epsilon fused to enhanced green fluorescent protein (EGFP) were transiently overexpressed in neuroblastoma cells. Overexpression of PKCepsilon-EGFP induced cell processes whereas the other isoforms did not. The effect of PKCepsilon-EGFP was not suppressed by the PKC inhibitor GF109203X. Instead, process formation was more pronounced when the regulatory domain was introduced. Overexpression of various fragments from PKCepsilon regulatory domain revealed that a region encompassing the pseudosubstrate, the two C1 domains, and parts of the V3 region were necessary and sufficient for induction of processes. By deleting the second C1 domain from this construct, a dominant-negative protein was generated which suppressed processes induced by full-length PKCepsilon and neurites induced during retinoic acid- and growth factor-induced differentiation. As with neurites in differentiated neuroblastoma cells, processes induced by the PKCepsilon- PSC1V3 protein contained alpha-tubulin, neurofilament-160, and F-actin, but the PKCepsilon-PSC1V3-induced processes lacked the synaptic markers synaptophysin and neuropeptide Y. These data suggest that PKCepsilon, through its regulatory domain, can induce immature neurite-like processes via a mechanism that appears to be of importance for neurite outgrowth during neuronal differentiation.

Actins↗
PubMed1999

Psychological well-being 3 years after severe stroke.

BACKGROUND AND PURPOSE: Stroke often has a very negative influence on the victims' perception of their life situation. The aim of this study was therefore to assess the subjects' long-term psychological well-being and to explore associations between subject characteristics, impairments, disabilities, and psychological well-being. METHODS: Of 100 subjects rehabilitated at a specialized geriatric stroke ward after the acute phase, 47 survivors were assessed in their homes 3 years after discharge and interviewed regarding their psychological well-being with the Philadelphia Geriatric Center Morale Scale (PGCMS). RESULTS: Sixty-four percent of the subjects were classified as having high scores for psychological well-being or fell within the middle range. In a cluster analysis, depression was shown to have the strongest association with the subjects' PGCMS scores. Variables including the subjects' social situation and functions as well as age, gender, ability to communicate, and need for help showed a much weaker association with the PGCMS. CONCLUSIONS: More than half of the stroke subjects were classified as having levels of psychological well-being that were good or fairly good. The strong association between PGCMS scores and depression indicates the importance of detecting and treating depression and of following up initiated therapy after stroke.

Cerebrovascular Disorders↗
PubMed1998

Inhibition of human and duck hepatitis B virus by 2',3'-dideoxy-3'-fluoroguanosine in vitro.

The fluorinated guanosine analog 2',3'-dideoxy-3'-fluoroguanosine (FLG) has been shown to have an effect on duck hepatitis B virus (DHBV) in vivo and in vitro. In this study the inhibitory effect of FLG on DHBV and human hepatitis B virus (HBV) was evaluated in vitro. Cell lines transfected either with DHBV or HBV DNA and primary duck hepatocyte cell cultures were used. Virus production was analysed by PCR and a quantitative PCR was established for DHBV for determination of the inhibitory concentrations of the drug. 50% inhibition was achieved with an FLG concentration of 0.2 microg/ml (0.7 microM) and 90% inhibition was observed with an FLG concentration of 1.0 microg/ml (3.7 microM) using the DHBV transfected cell line. FLG showed an effect on DHBV production in primary duck hepatocyte cell cultures at concentrations down to 0.1 microg/ml (0.4 microM). However, the DHBV production returned to pre-treatment levels within a few days after cessation of treatment. HBV production in transfected cell lines was also inhibited by FLG. Both DHBV and HBV DNA-polymerases were inhibited by FLG triphosphate and 50% inhibition was observed at a concentration of 0.05 microg/ml (0.1 microM) for DHBV and 0.03 microg/ml (0.05 microM) for HBV. FLG is an efficient inhibitor of DHBV replication both in vivo and in vitro and of HBV in vitro which makes it a good candidate for treatment of HBV infections. However, it does not completely eliminate the virus since a relapse in virus production was observed when treatment was withdrawn. Therefore it would be interesting to evaluate FLG in combination with other types of anti-HBV drugs.

Animals↗
PubMed1998

In-patient rehabilitation after stroke: outcome and factors associated with improvement.

A study aimed at examining the outcome of activities of daily living (ADL) of patients undergoing geriatric stroke rehabilitation was performed. Background and admission data of 99 patients surviving the acute phase and needing further hospital rehabilitation were registered. Forty per cent of the patients improved their ADL ability. The logistic regression modelling with the dichotomous dependent variable improvement versus no improvement showed the following factors associated with improvement: a diagnosis of intracerebral haemorrhage, male sex, high postural stability score at the admission and cohabitation. In conclusion, the most severely affected stroke patients, especially patients with intracerebral haemorrhage, have a great potential for improving their ADL. The results of the logistic regression model can serve as a useful guide when it comes to identifying patients that stand a fair chance of improving during their rehabilitation stay. Equally important, patients with a poor rehabilitation prognosis who may need intensified rehabilitation efforts to achieve optimum improvement can now be identified.

Activities of Daily Living↗
PubMed1996

2',3'-dideoxy-3'-fluoroguanosine inhibits duck hepatitis B virus in vivo.

Duck hepatitis B virus (DHBV) belongs to the same virus family as the human hepatitis B virus (HBV). Domestic ducks infected with DHBV can be used as an animal model for chronic hepatitis B virus infection in therapeutic trials. In this study the antiviral effect of the guanosine analogue 2',3'-dideoxy-3'-fluoroguanosine (FLG) was tried in vivo on chronically DHBV-infected ducks. The ducks were either congenitally infected, or inoculated with DHBV immediately post-hatch. FLG was given as intraperitoneal injections twice daily, at different dosages. Serum DHBV levels were determined by DNA dot-blot hybridization. A strong inhibition of serum DHBV DNA was observed with FLG doses down to 1 mg kg-1 day-1, given for 7 to 10 days. With the corresponding thymidine analogue, 2',3'-dideoxy-3'-fluorothymidine; however, no inhibition was obtained. This difference may be due to different phosphorylation mechanisms. Independently of FLG dose, serum DHBV DNA returned to pretreatment levels within a few days after cessation of therapy. After a long-term trial (FLG, 5 mg kg-1 day-1 for 33 days), the same relapse of DHBV production was seen. Thus, FLG is an efficient inhibitor of DHBV replication, and is a candidate for treatment of HBV infections. However, the effect is transient, and therefore combination with other types of anti-HBV drugs should be considered.

Animals↗
PubMed1993

Hepatitis C virus infection in hemodialysis patients in southern Sweden: epidemiological, clinical, and diagnostic aspects.

A prevalence of hepatitis C virus (HCV) antibodies of 12% was found in 276 patients from 11 dialysis units. Between zero and 22% of the patients in the different units were anti-HCV positive. The epidemiology of HCV was studied in two units during a 2 year period by antibody assays and the polymerase chain reaction and correlated with clinical manifestations. Two types of epidemiologic patterns were found that may explain the wide difference of HCV prevalence described in different dialysis units. In one unit there was no evidence of spread within the unit, and the prevalence of HCV was dependent on the status of the patients entering for treatment. In the other unit, a clustering of infected patients could be seen in which 13 of 36 were infected during a 3 year period. Some patients who had not received blood transfusions were among the infected. Hepatitis C infection was the most common explanation for repeated abnormal transferase levels. Most of the HCV-infected patients reacted both for anti-HCV and HCV RNA. HCV RNA was in general detected earlier than anti-HCV seroconversion. Among 20 HCV RNA-positive serum samples that were anti-HCV ELISA-positive 18 had indeterminate and two negative reactions by immunoblot (RIBA 2). Thus the RIBA 2 test should be used with caution as a confirmatory antibody test in this group of patients.

Alanine Transaminase↗
PubMed1993

Bronchoscopic diagnosis of pulmonary infections in a heterogeneous, nonselected group of patients.

Fiberoptic bronchoscopy with bronchoalveolar lavage and protected specimen brush technique has become an established method for etiologic diagnosis in severe forms of pulmonary infections during recent years. In this study, including 62 bronchoscopies in 53 patients, a standardized program, covering all important pulmonary pathogens, has been evaluated in a heterogeneous group of patients. Results providing therapeutic guidelines were obtained in 53 percent (16/30) of the immunocompromised patients (including 5 bronchoscopies on HIV-positive patients), but only 19 percent (6/32) of the immunocompetent patients (p < 0.001). We conclude that bronchoscopy is of great value for diagnosing pulmonary infections in immunocompromised patients. In immunocompetent patients, the diagnostic yield is lower and the indication for bronchoscopy must be established for each individual patient based on clinical importance, resources, and risk. When bronchoscopy is performed, we believe that a standardized program like ours reduces the risk of missing important pathogens.

AIDS-Related Opportunistic Infections↗
PubMed1991

Serum antibodies against respiratory tract viruses in episodes of acute otitis media.

Although the findings of epidemiological studies have suggested viral respiratory tract infection (RTI) to be crucially involved in the development of acute otitis media (AOM), the relationship between AOM and viral RTI remains unclear. Serum samples, obtained in the acute and convalescent phases of 57 AOM episodes (in 35 children during the first three years of life) were analysed for IgG antibodies against influenza A viruses, influenza B viruses, parainfluenza virus type 1, respiratory syncytial virus and adenoviruses. One third of the AOM episodes (18/57) could be related to viral RTI, as evidenced by significant increases in viral serum antibody activity. Treatment failure occurred in four AOM episodes where increases in serum viral antibody activity were noted. In three of these failures, antibiotic treatment was unsuccessful despite the bacterial strains not being resistant to the drug used. This suggests that concomitant viral infection may be a determinant of treatment outcome in some AOM episodes.

Acute Disease↗
PubMed1990

Responses to rubella, tetanus, and diphtheria vaccines in otitis-prone and non-otitis-prone children.

Delayed immunologic maturation--among other things based on a selective lack of antibodies against some acute purulent otitis media (AOM)-associated pneumococcal types--has been proposed in children with recurrent AOM (rAOM). To further elucidate the immunologic response in these children, we compared the antibody responses to diphtheria, tetanus, and rubella vaccinations in 13 children with rAOM and 29 children without AOM. The children took part in a prospective study from birth to the age of 3 years. The antibody response to the rubella vaccine was significantly lower in the children with rAOM. The responses to tetanus and to diphtheria did not differ between children with and without rAOM. Thus, the results indicate that in addition to the known lack of antibodies against pneumococcal polysaccharide antigens, a lower antibody response against at least one protein antigen may exist in otitis-prone children.

Antibody Formation↗
PubMed1990

Low frequency of hepatitis C antibodies among children from foreign countries adopted in Swedish families.

89 children from 20 countries adopted to Swedish parents between 1984 and 1988 were tested for the presence of hepatitis C antibodies (anti-HCV). Sera taken soon after their arrival to Sweden were retrospectively analyzed. Two children, an 18-month-old boy from Poland and an 8-month-old girl from India, were anti-HCV positive. The girl from India had lost the anti-HCV antibodies in sera taken at the age of 13 and 14 months. These antibodies were probably passively derived from the mother. The Polish boy had a strong positive reactivity and is likely to have had an HCV infection early in life. Thus, there is a low prevalence of anti-HCV positivity among children from foreign countries adopted in Swedish families.

Adoption↗
PubMed1989

Inhibition of RNA- and DNA-dependent duck hepatitis B virus DNA polymerase activity by nucleoside and pyrophosphate analogs.

The DNA polymerase of hepadnaviruses has two different functions during virus replication. It acts both as an RNA-dependent DNA polymerase (reverse transcriptase) and as a DNA-dependent DNA polymerase. Duck hepatitis B virus (DHBV) preparations were used to investigate the inhibitory effects of selected compounds on these two enzyme activities. The reverse transcriptase activity was represented by an actinomycin D-resistant, phosphonoformate-sensitive DNA polymerase activity isolated from DHBV-infected duck livers. DHBV from serum was used as the source of the DNA-dependent DNA polymerase activity. Pyrophosphate and nucleoside triphosphate analogs were assayed for their inhibitory effects on the two enzyme preparations. A marked inhibition was obtained with 3'-fluoro-2',3'-dideoxythymidine 5'-triphosphate, acyclovir triphosphate, 2',3'-dideoxythymidine 5'-triphosphate, 2',3'-dideoxyguanosine 5'-triphosphate and 2',3'-dideoxythymidine 5'-triphosphate. The two thymidine analog triphosphates showed a markedly lower inhibitory effect on the reverse transcriptase activity than on the DNA-dependent DNA polymerase activity. This was in analogy with earlier findings with 3'-azido-2',3'-dideoxythymidine 5'-triphosphate. Among the tested pyrophosphate analogs only phosphonoformate was inhibitory.

Animals↗
PubMed1989

Serum antibodies against respiratory tract viruses: a prospective three-year follow-up from birth.

Acute otitis media (AOM) has been epidemiologically related to viral respiratory tract infections, and viral antigens have also been detected in middle ear secretion in some AOM episodes. Successive serum samples from children followed prospectively for three years from birth were analysed for IgG antibodies against respiratory syncytial virus (RSV), adenoviruses and influenza A virus. Values from serum antibody activity gradually decreased during the first six months of life, followed by a gradual increase. Various relationships were found to obtain between age and the increases of antibody activity against the different viruses. Thus, three quarters of those tested had manifested increased antibody activity against RSV by 18 months of age, and against adenoviruses by 30 months of age. No increase of antibody activity against influenza A was noted before 12 months of age, and then only seen in two thirds of those tested during the entire three-year observation period. With regard to age, however, the proportion of children with increased antibody activity to RSV, adenoviruses or influenza A virus did not differ between otitis-prone and non-otitis-prone children. Thus, as compared to non-otitis-prone children, development of the ability to produce antibodies against these viruses was not found to be delayed in otitis-prone children.

Acute Disease↗
PubMed1988

Inhibition of human hepatitis B virus DNA polymerase and duck hepatitis B virus DNA polymerase by triphosphates of thymidine analogs and pharmacokinetic properties of the corresponding nucleosides.

Replication of hepadnaviruses involves a viral DNA polymerase containing both a DNA-dependent and an RNA dependent activity. This polymerase is a potential target for chemotherapy against hepatitis B. We have used human hepatitis B virus DNA-dependent DNA polymerase from human serum and duck hepatitis B virus DNA-dependent DNA polymerase from duck serum as well as RNA-dependent DNA polymerase activity from duck hepatitis B-infected duck liver. Triphosphates of thymidine analogs have been synthesized and tested for their inhibitory activities against these enzymes with the intention both to explore differences between these enzymes and structural requirements for inhibitors. The results showed that with the inhibitors tested, hepatitis B virus DNA-dependent DNA polymerase was the most sensitive enzyme and the triphosphate of 5-propenyl-2'-deoxyuridine was the most active inhibitor. In addition, the 5'-triphosphate of 5-propenyl-arabinofuranosyluracil also inhibited the hepadnavirus DNA-dependent DNA polymerases, and was a competitive inhibitor with respect to 2'-deoxythymidine triphosphate as showed by kinetic studies with duck hepatitis B virus DNA-dependent DNA polymerase from serum. Pharmacokinetic analysis showed 5-propenyl-2'-deoxyuridine to be well absorbed orally, but rapidly cleared from plasma. The arabinofuranosyl analog was also well absorbed but cleared less rapidly. Hence, these results indicate the potential of 5-propenyl-2'-deoxyuridine and 5-propenyl-arabinofuransyluracil for chemotherapy of hepatitis B.

Animals↗
PubMed1988

Varying antibody response in hospital staff vaccinated against hepatitis B.

Staff from a Department of Infectious Diseases (n = 64) were vaccinated against hepatitis B with HBVax (Merck, Sharp & Dohme), a plasma derived vaccine. Prevaccination testing showed a low prevalence of hepatitis B virus markers (1.4%). Only 1 person showed signs of anamnestic antibody response. Post-exposure prophylaxis and strict hygienic routines are recommended for non-operating hospital staff in areas with low prevalence of hepatitis B virus carriers. The anatomic site of intramuscular administration of the vaccine is discussed. The overall antibody response was low, 83% acquired a protective titer of anti-HBs and only 44% in the age group greater than 40 years of age. Postvaccination testing seems strongly advisable, especially in an older age group.

Adult↗
PubMed1987

Inhibition of hepatitis B virus DNA polymerase by 3'-azido-3'-deoxythymidine triphosphate but not by its threo analog.

An inhibitory effect of 3'-azido-3'-deoxythymidine triphosphate on hepatitis B virus DNA polymerase was found. No effect was seen by its threo analog. The effect was detected at and above a concentration of 0.05 microM. The inhibition of DNA polymerase activity was the same in ten different strains of HBV. The mechanism was shown to be competitive, with an inhibition constant (Ki) of approximately 0.04 microM, and the Km value for dTTP was 0.1 microM.

Antiviral Agents↗