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Biomedical subjects

H Bell

Publications and source records attributed to H Bell.

At least 37 records · Page 2Linked to original sources
PubMed1999

[Hemochromatosis--a rare cause of hypogonadism].

A 28-year-old man presented in 1992 with decreased libido and erectile dysfunction. He was found to have central hypogonadism with low serum levels of testosterone, LH and FSH. Computer tomography of the cella turcica was normal. Apart from hypogonadism, the pituitary function was normal. He was successfully treated with testosterone injections. In June 1995, elevated levels of serum ferritin (4,094 micrograms/l) and transferrin saturation (94%) raised suspicion of hemochromatosis. The diagnosis was confirmed by a percutaneous liver biopsy, and treatment started with regular phlebotomies. After three years of treatment the serum levels of LH and testosterone were normalized. Hypogonadism is, except for diabetes mellitus, the most frequent endocrine disturbance in hemochromatosis. It is found almost exclusively in male patients. It is important to exclude hypogonadism in male patients with hemochromatosis, but it is also important to exclude hemochromatosis in male patients with hypogonadism.

Adult↗
PubMed1999

High cytoplasmic expression in E. coli, purification, and in vitro refolding of a single chain Fv antibody fragment against the hepatitis B surface antigen.

A single-chain Fv (scFv) antibody fragment against the hepatitis B surface antigen (HBsAg) was expressed in Escherichia coli in the form of two independent fusion proteins, with either 60 ('long') or 27 ('short') amino acid N-terminal encoding sequences related to human interleukin-2. Both fusion proteins were expressed insolubly and at high levels in the bacterial cytoplasm (approximately 30% of total bacterial protein in MM294 cells at a laboratory scale). When recombinant cells were cultured in 5-1 fermentors, expression and optical density increased 2- and 4-fold, respectively, compared to a previous periplasmic insoluble version of the same anti HBsAg scFv. After extraction and solubilization in urea, the cytoplasmic scFvs were purified using immobilized metal ion affinity chromatography, followed by DTT treatment, and refolding by dialysis against a basic pH buffer containing EDTA. The refolded scFvs recognized the recombinant HBsAg in ELISA. Results of an ELISA where antigen affinity chromatography repurified scFvs were used as standards, indicated that refolding efficiencies were high: 56.2% for the 'short' fusion scFv, and 50.6% for the 'long' fusion scFv. Corrected final yields of active scFv were 30.3 and 27.3 mg l-1, respectively, for the aforementioned fusion proteins, 5-6 times better than those reported for the periplasmic scFv variant.

Amino Acid Sequence↗
PubMed1999

Heritable thrombophilia and hypofibrinolysis. Possible causes of retinal vein occlusion.

OBJECTIVE: To determine whether heritable thrombophilia and hypofibrinolysis were risk factors for retinal vein occlusion. DESIGN: Measures of thrombophilia (increased likelihood of thrombus formation) included anticardiolipin antibodies (IgG and IgM), the lupus anticoagulant (including dilute Russell viper venom clotting time), antigenic proteins C and S, and homocysteine. Polymerase chain reaction assays were performed for 3 thrombophilic gene mutations (factor V Leiden, methylenetetra-hydrofolate reductase, and prothrombin gene). Measures of hypofibrinolysis (reduced ability to lyse thrombi) included lipoprotein Lp(a), plasminogen activator inhibitor activity, and polymerase chain reaction analysis of the hypofibrinolytic 4G/5G polymorphism of the PAI1 gene. These coagulation measures were performed in 17 patients with retinal vein occlusions with comparison with serologic coagulation measures and polymerase chain reaction assays in 40 and 234 healthy normal volunteers as controls, respectively. RESULTS: Of 14 patients with retinal vein occlusion with measures of dilute Russell viper venom clotting time, a thrombophilic antiphospholipid antibody, 6 (43%) had abnormal results (> 38.8 seconds) compared with 1 (3%) of 30 controls (P = .002). Of 17 patients with vein occlusion, 3 (18%) were heterozygous for the thrombophilic factor V Leiden G1691A mutation compared with 7 (3%) of 233 controls (P = .02). Of 17 patients with vein occlusion, 2 (12%) had normal alleles (5G/5G) for the plasminogen activator inhibitor gene promoter; the other 15 (88%) were heterozygous or homozygous for the 4G polymorphism, which is associated with hypofibrinolysis. Of 234 controls, 85 (36.3%) had the 5G/5G allele; 149 (63.7%) were heterozygous or homozygous for the 4G polymorphism (P = .03). Patients with vein occlusion were more likely to have high levels of the major determinant of hypofibrinolysis, plasminogen activator inhibitor activity. These levels were high (> 22 U/L) in 6 (38%) of 16 patients with vein occlusion compared with 1 (2%) of 40 controls (chi 2 = 12.8; P = .001). Patients with vein occlusion were more likely (8/16 [50%]) to have high levels of hypofibrinolytic Lp(a) (> 35 mg/dL) than controls (5/40 [13%]; chi 2 = 9; P = .003). The median Lp(a) level in patients with vein occlusion who had the 4G/4G genotype was 62 mg/dL compared with 5.3 mg/dL in controls with the 4G/4G genotype (P = .05). CONCLUSION: Thrombophilia and hypofibrinolysis are possible causes of retinal vein occlusion.

Adult↗
PubMed1999

Immunohistochemical detection of oestrogen and progesterone receptors in salivary tumours.

The purpose of this study was to determine the oestrogen and progesterone receptor status of a selection of salivary tumours. Using immunohistochemistry, we detected nine oestrogen receptor and six progesterone receptor positive tumours from a sample of 36. One acinic cell carcinoma and two mucoepidermoid carcinomas demonstrated positivity for both receptors. We suggest that there may be role for oestrogen manipulation in the management of some salivary tumours.

Female↗
PubMed1999

Treatment with interferon-alpha2a alone or interferon-alpha2a plus ribavirin in patients with chronic hepatitis C previously treated with interferon-alpha2a. CONSTRUCT Group.

BACKGROUND: Preliminary results from combination therapy with interferon-alpha and ribavirin (IFN/Rib) in patients with chronic hepatitis C have been promising, with up to 50% sustained hepatitis C virus (HCV) RNA response. The aim of this study was to investigate whether a sustained HCV RNA response could be obtained with combination therapy in patients who were non-responders or relapsers after IFN treatment. METHODS: In a multicenter study we randomized 53 HCV RNA-positive patients into 2 treatment groups. They all had biopsy-confirmed chronic hepatitis C, and all were recruited from a previous IFN study: 26 were previous non-responders and 27 responders with relapse. Group A received interferon-alpha2a, 4.5 MIU thrice weekly for 6 months, and group B received ribavirin, 1000-1200 mg/day, in combination with the same dose of interferon-alpha2a for 6 months. Median Knodell index was 5.0 in both groups. Genotype 1 was found in 24 (45%), type 2 in 3 (6%), and type 3 in 26 (49%). RESULTS: Sustained clearance of HCV viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53 patients (23%): 6 of 27 in the IFN group (22%) and 6 of 26 (23%) in the IFN/Rib group (NS). Nine of 27 (33%) former responders with relapse, compared with 3 of 26 (12%) non-responders, obtained a sustained HCV RNA response (P = 0.054). In previous relapse patients sustained loss of viremia was more frequent in genotype 3 (50%) than in genotype 1 (11%) patients (P = 0.022). CONCLUSIONS: In a group of previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained clearance of viremia when retreated either with IFN-alpha2a alone or with a combination of IFN-alpha2a and ribavirin for 6 months. Previous relapse patients with HCV genotype 3 obtained sustained loss of viremia significantly more often (50%) than type-patients (11%). Previous IFN responders with relapse responded better than previous non-responders.

Adult↗
PubMed1999

High prevalence of the hemochromatosis-associated Cys282Tyr HFE gene mutation in a healthy Norwegian population in the city of Oslo, and its phenotypic expression.

BACKGROUND: Previous studies have shown that 5%-10% of white subjects are heterozygous for the HFE gene C282Y mutation, which is associated with hemochromatosis. The aim of our study was to determine the prevalence of heterozygosity and homozygosity for the C282Y HFE gene mutation and its phenotypic expression in a group of healthy Norwegians. METHODS: Fasting blood samples were obtained from 505 unrelated hospital employees. Serum iron, transferrin, and serum ferritin were measured. Transferrin saturation was calculated. The presence of HFE gene mutation was determined with a polymerase chain reaction-based analysis. RESULTS: Two of the 505 subjects (0.4%) were homozygous and 75 (14.9%) were heterozygous for the C282Y mutation. Median serum ferritin among the heterozygotes was 59 microg/l, compared with 47 microg/l among individuals without the C282Y mutation (P = 0.12). Median transferrin saturation among the heterozygotes was 31%, compared with 24% among individuals without C282Y mutation (P < 0.001). Twenty-three individuals (4.6%) had a serum ferritin level > 200 microg/l. Eight of these (35%) had the C282Y mutation: two homozygotes and six heterozygotes. Transferrin saturation > 50% was observed in 25 individuals (5.0%). Twelve of these (48%) had the C282Y mutation; two were homozygotes and 10 heterozygotes. Only eight individuals (1.6%) had a transferrin saturation > 60%: one homozygote, five heterozygotes, and two individuals without mutation. CONCLUSIONS: Fifteen per cent of a healthy Norwegian population is heterozygous for the HFE gene mutation C282Y. This is among the highest reported prevalence values among healthy individuals. Half of the subjects with transferrin saturation greater than 50% were carriers of the C282Y mutation.

Adult↗
PubMed1999

Utilization of endoscopic inoculation in a mouse model of intrauterine infection-induced preterm birth: role of interleukin 1beta.

A novel murine model of intrauterine infection/inflammation-induced preterm birth based on direct endoscopic intracervical inoculation is described. Using this model, we investigated infection-induced premature pregnancy loss in normal and interleukin (IL) 1beta-deficient mice. Seventy-four CD-1, HS, C57BL/6J wild type (IL-1beta+/+), and C57BL/6J IL-1beta-deficient (IL-1beta-/-) mice were inoculated intracervically using a micro-endoscope, at a time corresponding to 70% of average gestation. Intracervical injection of lipopolysaccharide (LPS) or Escherichia coli reliably induced premature birth: 100% of mice intracervically injected with LPS and 92% of mice with a positive endometrial E. coli culture delivered prematurely within 36 h after inoculation. No losses were observed in mice inoculated with saline. Pregnancy loss was associated with increased uterine tissue cyclooxygenase-2 gene expression and uterine content of IL-1beta, tumor necrosis factor alpha, macrophage inflammatory protein-1alpha, and IL-6, as well as elevation of nuclear factor-kappaB activity in uterine tissues. Although IL-1beta-/- mice exhibited decreased uterine cytokine production in response to bacteria and LPS, IL-1beta deficiency did not affect the rate of pregnancy loss. This model using direct intracervical bacterial or LPS inoculation is useful for studying preterm pregnancy loss in genetically altered mice in order to develop novel interventions for infection-associated preterm labor.

Animals↗
PubMed1998

Neuropathological findings after intracerebral implantation of microdialysis catheters.

The neuropathological and immunocytochemical changes in the sheep forebrain following 7 days of microdialysis, using a catheter approved for human use, are described. There was no behavioural dysfunction and light microscopy revealed mild astrogliosis and patchy macrophage infiltration immediately adjacent to the catheter track. The surrounding neuropil was normal. There was one small subcortical haemorrhage (10 x 1.5 mm). These findings are similar to those following microdialysis in rodents and suggest that the risk of significant damage to the human brain is low, that neuropathological changes in the brain around the catheter should not interfere with local brain metabolism, and that the catheter should be affixed in such a way as to minimize movement-induced damage to the brain.

Animals↗
PubMed1998

Liposomal transfection efficiency and toxicity on glioma cell lines: in vitro and in vivo studies.

To evaluate the influence of cell type and cationic liposomal formulation on gene transfection efficiency three liposomes (lipofectin, lipofectamine and DOTAP) were used to transfect the human (A172 and MOG-G-CCM) and rodent (C6 and A15A5) glioma cell lines with the Lac Z gene. Parallel studies evaluated in vitro cytotoxicity and the neuropathological changes following intracerebral injection. The transfection efficiency and cytotoxicity of the liposomes varied both quantitatively and qualitatively between the cell lines. There were no behavioural disturbances following intrastriatal or hippocampal injection and the neuropathological changes at the injection sites were focal and similar for all liposomes. The influence of glial cell lineage on both liposomal transfection facility and cytotoxicity may have important implications for in vivo gene transfection in the central nervous system.

Animals↗
PubMed1998

[Genetic diagnostic test for hemochromatosis].

Haemochromatosis is an inherited, recessive trait and is among the most common genetic diseases in Norway. It is caused by a pathological increase in the absorption of iron from the intestine. This in turn leads to excessive deposits of iron in the organs of the body, e.g. in the liver and pancreas, with concomitant symptoms and frequently organ failure. The mutated gene (HFE), which causes the vast majority of cases of haemochromatosis, has recently been described in a study from the U.S. Based upon this finding, we have established a genotyping protocol for this mutation. We discuss our preliminary experiences using this test as a diagnostic tool, as well as the implications of how it will affect diagnosis. The test is of considerable value, and we suggest that its use should be mandatory in the diagnosis of haemochromatosis.

Adult↗
PubMed1998

Detection of GB virus C RNA by GBV-C LCx and two PCR assays with primers from the 5' non-coding and NS5B region.

The objective of this study was to compare the sensitivity of three different reverse transcriptase-polymerase chain reaction (RT-PCR) based tests, for detection of GB virus C (GBV-C) RNA. One commercial and two 'in house' RT-PCR assays were employed in the testing of serum samples from 114 chronic hepatitis C infected individuals. A part of the 5' non-coding region (5'NCR) of the GBV-C genome was amplified by the GBV-C LCx assay (Abbott) and one of the 'in house' RT-PCR tests. In the other 'in house' RT-PCR a segment of the NS5B region was amplified. The 'in house' assays included the use of internal controls that were co-amplified with use of the same outer PCR primers as the virus targets. The GBV-C LCx from Abbott and 5'NCR 'in house' PCR tests detected 28 and 27 GBV-C positive individuals, respectively. The sample positive only in the LCx test was confirmed by the 'in house' 5'NCR RT PCR using an increased virus input. In comparison, the NS5B 'in house' PCR test detected 24 of the GBV-C positive samples. One sample showed no amplification of internal controls/virus target in the 5'NCR 'in house' PCR and another samples was amplification negative in the NS5B PCR. The PCR assays with primers from the 5'NCR of the virus genome e.g. the GBV-C LCx, were more sensitive compared with RT-PCR using primers from the NS5B region. The GBV-C LCx seemed to be the most sensitive and robust assay. Internal controls included in the 'in house' assays identified two samples with failure of the amplification.

5' Untranslated Regions↗
PubMed1998

Incidence and prevalence of primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis in a Norwegian population.

BACKGROUND: The relative frequencies of the autoimmune liver diseases primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), and autoimmune hepatitis (AIH) have not been studied. We therefore performed an epidemiologic investigation to describe the incidence and prevalence of the three diseases in a defined population. METHODS: Patients with PBC, PSC, or AIH admitted to Aker University Hospital in Oslo were prospectively registered during the 10-year period 1986-95. This hospital serves a defined population of 130,000 inhabitants. The mean yearly incidence and the point prevalences at the end of each year were calculated. RESULTS: During the 10-year period 21 patients with PBC, 17 with PSC, and 25 with AIH were diagnosed. The mean annual incidence per 100,000 was 1.6 for PBC, 1.3 for PSC, and 1.9 for AIH. The point prevalences per 100,000 on 31 December 1995 were 14.6, 8.5, and 16.9 for PBC, PSC, and AIH, respectively. CONCLUSIONS: The prevalences of PBC and AIH are of the same order of magnitude and about twice as high as that of PSC. These epidemiologic data can be used to estimate the number of liver transplantations required due to autoimmune liver diseases.

Adolescent↗
PubMed1998

The effect of treatment with alpha-interferon on hepatitis G/GBV-C viraemia. The CONSTRUCT Group.

BACKGROUND: Hepatitis G virus (HGV) or GBV-C is frequently detected in patients co-infected with hepatitis C virus (HCV). This study investigated host and virologic factors influencing the response to HGV/GBV-C to alpha-interferon treatment. METHODS: HGV/GBV-C was detected and quantified by nested polymerase chain reaction. The influence of variables such as liver biopsy appearance, liver function abnormalities, and response of HCV to interferon treatment was monitored. RESULTS: Fourteen of the 25 HGV/GBV-C-infected patients treated with interferon (3-6 MIU three times a week for 6 months) became non-viraemic during treatment, although all relapsed after treatment withdrawal at 6 months, with no net change in virus load between 0 and 12 months. CONCLUSIONS: Predictive factors for clearance of HGV/GBV-C viraemia by interferon were pre-treatment severity of liver disease (median Knodell score of 4, compared with 7 for non-responders; P = 0.030) and alanine aminotransferase levels (median, 114, 182 for non-responders; P = 0.039). Clearance was associated with the treatment response of HCV. Nine of 13 who cleared HGV/GBV-C also cleared HCV, compared with 3 of 11 HGV/GBV-C non-responders; P = 0.05). The shared susceptibility of HGV/GBV-C and HCV to interferon treatment suggests a link between the mechanism of clearance of the two viruses.

Adult↗
PubMed1998

Prolonged nosocomial outbreak of hepatitis A arising from an alcoholic with pneumonia.

From April to June 1996, an outbreak of hepatitis A virus (HAV) infection affecting 15 nurses, patients and household contacts occurred in the Department of Internal Medicine at Aker University Hospital, Oslo. The index case was a homeless alcoholic who was hospitalized in March 1996 with pneumonia while simultaneously incubating HAV infection. Four secondary cases were infected by the index case, while another 10 cases were caused by a continuous spread of infection within the department during the following months. Sequence of the VP1/P2A junction of HAV was obtained from 9 patients, including the index case, and all sequences were identical to each other. Mass vaccination of hospital employees with a formalin-inactivated HAV-vaccine took place in late May, and following this the outbreak stopped. Several factors probably combined to account for this unusual outbreak, e.g. an index case unsuspected of incubating with HAV infection, and a low prevalence rate of protective antibodies to HAV among the hospital staff.

Adult↗
PubMed1998

Summary report on the ISOBM TD-6 workshop: analysis of 20 monoclonal antibodies against Sialyl Lewisa and related antigens. Montreux, Switzerland, September 19-24, 1997.

The ISOBM TD-6 Workshop is the first international workshop on monoclonal antibodies against the Sialyl Lewisa (SLea) antigen. Eight research groups participated in a blind study to characterize the epitope binding, relative affinity and performance in immunoradiometric assays, of a panel of 20 monoclonal antibodies. The antibodies were tested against a diverse panel of neoglycoconjugates, purified antigens and human serum pools from gastrointestinal malignancies. Epitope specificities were determined for the majority of antibodies in the panel. Cross-reactivity with related saccharide structures was noted in several antibodies. Overall, the results of the TD-6 Workshop show further development of SLea immunoassays may yield yet more specific assays for the detection and management of gastrointestinal and other malignancies.

Antibodies, Monoclonal↗