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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 55 records · Page 3Linked to original sources

A new test for immunological infertility: an ELISA based on prostasomes.

Antisperm antibodies (ASA) are present in patients with immunological infertility, but the antigens are poorly characterized. Prostasomes adhere to sperm cells and are recognized as antigens for ASA. This investigation aimed to study the prevalence of antiprostasome antibodies in ASA-classified sera. We studied the reactivity of ASA-positive sera from 116 immunoinfertile patients. Ninety-seven per cent (113 of 116) of the patients' sera contained IgG antibodies against seminal prostasomes. Accordingly, prostasomes are one of the major targets for ASA. An enzyme-linked immunosorbent assay based on prostasomes is simpler to perform than ASA tests presently in use. It is also easier to achieve reproducible and standardized results.

Antibodies↗

Prostasome antigens as targets for sperm agglutinating antibodies demonstrated by 1-D gel electrophoresis and immunoblottings.

Many immunoinfertile men have sperm agglutinating antibodies that are directed against prostasome-derived antigens, but these antigens have not been defined so far. We selected serum samples with high ELISA titres against prostasomes from a group of immunoinfertile patients with sperm agglutinating antibodies and used the sera for immunoblottings on 1-D SDS-PAGE of prostasomes and sperm cells. The immunoblottings with individual antiprostasome antisera on 1-D SDS-PAGE of prostasomes, revealed three to 10 bands for each serum. Eighty-five per cent of the serum samples contained bands in the 70-75 kDa region and 80% of the samples contained bands in the 50-55 kDa region. Immunoblottings of extracted sperm cells, revealed one to six bands in the molecular weight range 25-82 kDa and two of the samples recognized two bands with molecular weights (50 and 43 kDa) similar to immunoblottings of prostasomes. The prostasomal antigens recognized by the high titre-antisera of immunoinfertile men were generally different from the sperm antigens recognized by the same sera. This suggests that prostasomes offer a new set of antigens available for research on male immunoinfertility and immunocontraception.

Antigens↗

Growth factor analysis of low-grade glioma CSF: PDGF and VEGF are not detectable.

Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) are involved in the development of grade 2 gliomas. The aim of the present study was to determine the presence of these growth factors in the cerebrospinal fluid (CSF) and to assess their usefulness as biological markers. CSF was collected from 7 adult patients with newly diagnosed supratentorial low-grade gliomas by lumbar puncture and was analysed together with matched serum samples using radioreceptor and enzyme-linked immunosorbant assays. Neither PDGF nor VEGF were detected in the CSF, and FGF-2 was measurable at extremely low concentrations in only 2 of 7 patients. Serum levels were within normal limits. We conclude that these growth factors are not released into the CSF in any significant amounts and are therefore not suitable as biological markers in grade 2 gliomas.

Adolescent↗

A lung recruitment maneuver immediately before rescue surfactant therapy does not affect the lung mechanical response in immature lambs with respiratory distress syndrome.

BACKGROUND: In animals with acquired surfactant-deficiency, a recruitment maneuver by increased tidal volumes enhances the effect of exogenous surfactant. In contrast, in the preterm lamb model, hyperinflation early after birth impairs the effect of surfactant prophylaxis. Here we examined whether a lung recruitment maneuver just before surfactant would affect the response to rescue treatment in immature lambs with established respiratory distress syndrome (RDS). METHODS: Five pairs of preterm twin lambs with gestational age 127 days were delivered by cesarean section and supported by pressure-limited mechanical ventilation for 4 h. At 30 min of age, when all the lambs were in severe respiratory failure, they were treated with porcine surfactant, 200 mg x kg-1. One lamb in each pair was subjected to a lung recruitment maneuver consisting of five sustained inflations of 20 ml x kg-1 just before surfactant instillation. RESULTS: At 10 min after surfactant treatment, all the lambs showed a large improvement in oxygenation and an increase in inspiratory capacity and static compliance. Except for a transiently better oxygenation after surfactant therapy in the recruitment group (P < 0.05), there was no significant between-group differences in gas exchange or lung mechanics at any time point during the study. There was no difference in post mortem intrapulmonary air volume or alveolar expansion in histologic lung sections between groups. CONCLUSION: This small study does not show any positive or negative effect of a lung recruitment maneuver on the response to rescue surfactant therapy in immature animals with RDS.

Animals↗

A case of multiple AOT-like jawbone lesions in a young patient--a new odontogenic entity?

We assessed the immunohistochemical profile of an unusual case of multiple similarly looking tumors in the jawbone of a young patient. Histologically, the tumors exhibited features of adenomatoid odontogenic tumor (AOT) and adenomatoid dentinoma but showed no resemblance to any other defined odontogenic tumor entities. They expressed high amounts of cytokeratin (CK) 8 and 14 together with some Vimentin. A small rim of peripheral cells showed CK 5, 17, and 19 reactivity. Also, these lesions expressed some bcl-2 as well as p53 and Ki67. Histologically and immunohistochemically, the unusual multiple lesions differed in details from a simultaneously examined group of 24 classical AOT cases, suggesting that they may represent a hitherto less well-defined odontogenic tumor entity.

Antigens, Neoplasm↗

A new flow cytometric method for measurement of von Willebrand factor activity.

BACKGROUND: Patients with von Willebrand's disease may have normal levels of von Willebrand factor (VWF) antigen. It is therefore important to measure not only the antigen concentration but also the VWF activity. The most widely used method for measurement of VWF activity is the ristocetin cofactor assay (VWF:RCo), which is still crucial for the laboratory diagnosis of von Willebrand's disease (VWD). However, VWF:RCo has low precision, poor inter-laboratory reproducibility and requires an aggregometer. Many routine laboratories are not equipped with aggregometers but have flow cytometers instead. METHODS: In this study a simple, precise and rapid flow cytometric assay was developed for the determination of von Willebrand factor activity, utilizing formalin-fixed platelets, fluorescein isothiocyanate-conjugated chicken anti-VWF antibodies (Fab-fragments) and phycoerythrine-conjugated anti-GPIIb/IIIa antibodies. RESULTS: In samples from healthy controls and from patients with von Willebrand disease type 1, the flow cytometry assay showed good correlation with the VWF:RCo assay (r2 = 0.69) and the VWF antigen assays (r2 = 0.83), which was better than the correlation between the VWF:RCo assay and VWF antigen assays (r2 = 0.72). The flow cytometry method had good within-assay and total precision, C.V. 4.2%, and C.V. 7.5%, at a mean concentration of 0.40 IU/mL, respectively. Results obtained with the flow cytometric method on samples from two patients with von Willebrand disease 2B were lower than those obtained with the antigen method in accordance with the diagnosis. CONCLUSION: The accuracy and precision of the von Willebrand activity assay may be improved if a flow cytometer is utilized for measurement of the impact of ristocetin on binding of VWF to formalin-fixed platelets instead of measuring agglutination utilizing an aggregometer. In addition, our flow cytometric method assay enables measurement of von Willebrand factor activity at many more hospitals than was previously possible with the traditional ristocetin cofactor platelet aggregometry assay, and this trend is likely to increase in the future when routine hematological instruments are equipped with built-in flow cytometers.

Antibodies↗

A method for attenuation and scatter correction of brain SPECT based on computed tomography images.

A method for attenuation and scatter correction of brain single photon emission computed tomography (SPECT) is described where computed tomography (CT) images of the brain are used for the calculation of attenuation maps. The method is evaluated for the substance 99mTc hexamethylpropylene amine oxime. A transmission dependent scatter correction is utilized and is based on ray sums calculated through the attenuation map. A method based on external markers is used to align the SPECT and CT image volumes. The markers need only to be present during the SPECT acquisition since the corresponding landmarks can be found without markers on the CT images. The mismatching has been investigated for five patients who have undergone both a CT examination and a SPECT examination with markers. Twelve individuals from the staff have pointed out the landmarks on the CT images, with an average standard deviation of 3.4 mm. Reconstructions with an attenuation map shifted the corresponding 95% confidence interval have been performed to obtain an estimation of the quantitative uncertainty caused by the mismatching, and quantitative errors of up to 6.3% have been measured. At present the method is probably most useful when groups of patients are studied.

Algorithms↗

Microdialysis-evaluated myocardial cyclooxygenase-mediated inflammation and early circulatory depression in porcine endotoxemia.

OBJECTIVE: To evaluate the early myocardial biochemical inflammatory response with the microdialysis technique during porcine endotoxemia and to simultaneously monitor systemic hemodynamics. DESIGN: Prospective, randomized, placebo-controlled trial with parallel groups. SETTING: Animal research laboratory at the University Hospital of Uppsala, Sweden. SUBJECTS: Thirteen piglets aged 12-14 wks receiving general anesthesia. INTERVENTIONS: After thoracotomy and the insertion of microdialysis probes in standardized locations in the left ventricle of the heart and in the quadriceps muscle, seven pigs received a continuous infusion of endotoxin, initiating a severe endotoxemic shock. Six pigs received saline instead of endotoxin. MEASUREMENTS AND MAIN RESULTS: Endotoxemia caused a rapid and pronounced elevation of a metabolite obtained from prostaglandin degradation, 15-keto-dihydro-PGF(2alpha), in myocardial microdialysate fluid being specific of cyclooxygenase (COX)-mediated inflammation (p <.001 vs. saline-infused controls). Simultaneously, we observed a decrease in left ventricular stroke work index in the endotoxemic pigs (p <.01 vs. saline-infused controls). Endotoxemia did not alter 15-keto-dihydro-PGF(2alpha) levels in quadriceps muscle. Endotoxemia caused increases in taurine, hypoxanthine, and magnesium in myocardial microdialysate (p <.05 vs. saline-infused controls), whereas the contents of pyruvate, lactate, inosine, adenosine, and calcium were not significantly changed. CONCLUSION: Endotoxemia induced a myocardial COX-mediated inflammation without signs of ischemia. In parallel, a depletion of myocardial energy substrates and a deterioration in myocardial performance were seen.

Analysis of Variance↗

Serum amyloid A: a novel serum marker for the detection of systemic inflammatory response in cystitis.

PURPOSE: We compared serum amyloid A (SAA) protein, C-reactive protein (CRP), interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha as inflammatory markers for pyelonephritis and cystitis. MATERIALS AND METHODS: SAA, CRP, IL-6 and TNF-alpha were determined in serum from 69 consecutive patients with acute pyelonephritis (37) and acute cystitis (32) on admission to an infectious disease clinic and on examination at a primary health care center, respectively. Healthy blood donors served as controls. RESULTS: SAA showed a systemic inflammatory response in cystitis in 90% of patients compared with 23%, 42% and 0% for CRP, IL-6 and TNF-alpha, respectively. SAA and CRP had equally high efficiencies (0.96 and 0.94, respectively) for discriminating between pyelonephritis and cystitis while efficiencies for IL-6 (0.85) and TNF-alpha (0.91) were lower. CONCLUSIONS: SAA is a sensitive systemic marker in cystitis but is still useful in detecting pyelonephritis.

Adult↗

High sensitivity CRP and serum amyloid A as expressions of low grade inflammation do not correlate with bFGF or VEGF.

High sensitivity CRP (hsCRP) and serum amyloid component A (SAA) are two acute phase proteins that have been shown to be prognostic markers in cardiovascular diseases. Vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) are two angiogenic growth factors involved in the growth and invasion of solid tumors and hematological malignancies. They also play an important role in cardiovascular and inflammatory diseases. The acute phase response induces the production of angiogenic peptides and angiogenic peptides have also been shown to induce the synthesis of inflammatory cytokines. HsCRP and SAA, bFGF and VEGF in serum and EDTA plasma were measured in samples from 80 human blood donors. There were strong correlations between hsCRP and SAA but there were no significant correlation between hsCRP or SAA and any of the angiogenic peptides. Low-grade inflammation did not induce bFGF or VEGF production.

Adult↗

Correlations between serum amyloid A protein and C-reactive protein in infectious diseases.

Serum amyloid A (SAA) protein is an acute phase reactant that has recently become of increasing interest as a marker for disease and treatment monitoring. We have correlated SAA levels to those of C-reactive protein (CRP) in sera from 98 patients admitted to an infectious diseases clinic because of viral and bacterial infections, including hepatitis A and B, cytomegalovirus infection, varicellae-zoster, infectious mononucleosis, influenza A, bacterial pneumonia, streptococcal pharyngitis, bacterial sepsis and severe bacterial sepsis. The study population was chosen from the clinical setting as representatives of these frequently encountered patient groups. SAA levels correlated significantly with CRP levels (r2=0.757, p<0.001) for the entire studied population. Furthermore, positive correlations were found in viral (r2=0.572, p<0.001) and bacterial (r2=0.666, p<0.001) infections. Positive correlations were also observed when the values were compared in accordance with CRP levels higher and lower than 100 mg/L (r2=0.689, p<0.001; CRP>100; r2=0.397, p<0.001; CRP<100). Because SAA is more sensitive than CRP for the detection of minor inflammatory stimuli, as in the viral and low CRP groups, we conclude that SAA can be of use in several viral infections, as well as in non-invasive and early invasive bacterial infections.

Bacterial Infections↗

Elevated preoperative serum levels of angiogenic cytokines correlate to larger primary tumours and poorer survival in non-small cell lung cancer patients.

We have analysed the predictive and prognostic information in preoperatively collected serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients clinically evaluated as operable non-small cell lung cancer (NSCLC). Fifty-eight patients with operable NSCLC were included. VEGF and bFGF levels in serum were analysed using enzyme linked immunosorbent assays (Quantikine human VEGF and Quantikine HS human FGF basic, R&D Systems). Univariate analysis demonstrated that tumour volume, platelet counts, VEGF and bFGF were significant prognostic factors. However, only bFGF remained significant in the multivariate analysis (P=0.014). Significant correlation's were demonstrated between VEGF levels and tumour volume (r=0.33; P=0.012) and platelet count (r=0.43; P=0.001). bFGF levels correlated significant with recurrent disease (r=0.34; P=0.01), platelet count (r=0.53, P<0.001) and performance status (r=0.29; P=0.029). Furthermore, bFGF levels and VEGF levels correlated significantly (r=0.44; P<0.001). We conclude that elevated circulating angiogenic cytokines correlate with tumour volume, higher relapse risk and poorer survival in patients with operable non-small cell lung cancer.

Adult↗

Oxidative stress in inborn errors of metabolism: lessons from glutathione deficiency.

Oxidative stress has been thought to be involved in the pathogenesis of several inborn errors of metabolism, such as mitochondrial enzyme deficiencies, G6PD deficiency, methylmalonic acidaemia and PKU. The possible role of oxidative stress in the pathogenesis of inborn errors of metabolism is discussed in the light of inborn errors in the metabolism of glutathione.

Glutamate-Cysteine Ligase↗

Serum and plasma levels of FGF-2 and VEGF in healthy blood donors.

VEGF-A and FGF-2 are two angiogenic growth factors involved in the growth and invasion of solid tumours and haematological malignancies. They are also believed to play an important role in cardiovascular and inflammatory diseases. Several studies dealing with measurement of circulating FGF-2 and VEGF have been published during the last decade. We have studied the levels of FGF-2 and VEGF-A in serum and EDTA plasma from 80 healthy blood donors. The samples were analyzed using the most widely used and commercially available ELISAkits. There was no significant effect of age on any of the assays and no effect of sex on P-FGF-2, S-VEGF-A and P-VEGF-A. Using the 97.5th percentile we obtained the following reference values: P-FGF-2 < 6.4 ng/l; S-VEGF-A < 500 ng/l; P-VEGF-A < 80 ng/l. Separate gender based reference intervals were made for S-FGF-2 as women had significantly higher S-FGF-2 values. Reference values for S-FGF-2 were <4.0 ng/l (men) and <10.8 ng/l (women).

Adult↗

Glutathione synthetase deficiency: is gamma-glutamylcysteine accumulation a way to cope with oxidative stress in cells with insufficient levels of glutathione?

Glutathione (GSH) plays a major role in the cellular defence against oxidative stress and other vital cellular functions. It therefore seems inevitable that patients with severe depletion of GSH will not survive. However, at least some with glutathione synthetase (GS) deficiency do. This study was done to determine whether these patients have a mechanism to compensate for their GSH deficiency. Cell-free extracts of cultured fibroblasts from 9 patients with GS deficiency and 9 control subjects were analysed by HPLC for low-molecular-weight thiol compounds. The patients' cells contained 7.4 nmol of GSH per mg of protein (median; range 2.8-25.2) compared to 33.0 nmol in control fibroblasts (range 26.7-51.4) (p < 0.01). On the other hand, the patients' cells accumulated 18.1 nmol of gamma-glutamylcysteine (gamma-GC) per mg of protein (median; range 6.9-71.7), whereas the control cells contained 0.1 nmol (range 0.05-0.16) (p < 0.01). The cysteine concentrations in the patients' cells were 20.7 nmol/mg protein (median; range 9.4-52.9) compared to 8.9 nmol in control cells (range 3.0-12.4) (p < 0.01). Cultured fibroblasts from patients with GS deficiency have low levels of GSH, but instead accumulate gamma-GC. We suggest that gamma-GC, which contains both reactive groups of GSH (i.e. the sulphydryl and gamma-glutamyl groups), can compensate for GSH in the cellular defence against oxidative stress. Thus, gamma-GC may alleviate, but only partly prevent, serious consequences of insufficient GSH levels in affected patients. Since the sum of the levels of GSH and gamma-GC in GS-deficient cells (median 31.5 nmol/mg protein, range 16.2-79.0) was similar to the level of GSH alone in control cells (33.0 nmol/mg protein, range 26.7-51.4), we propose that the cultured fibroblasts may have a mechanism to regulate in a coordinated way the levels of GSH and gamma-GC; for instance, by both compounds acting as feedback inhibitors of gamma-GC synthetase.

Adolescent↗

Airway closure in anesthetized infants and children: influence of inspiratory pressures and volumes.

BACKGROUND: Cyclic opening and closing of lung units during tidal breathing may be an important cause of iatrogenic lung injury. We hypothesized that airway closure is uncommon in children with healthy lungs when inspiratory pressures are kept low, but paradoxically may occur when inspiratory pressures are increased. METHODS: Elastic equilibrium volume (EEV) and closing capacity (CC) were measured with a tracer gas (SF(6)) technique in 11 anesthetized, muscle-relaxed, endotracheally intubated and artificially ventilated healthy children, aged 0.6-13 years. Airway closing was studied in a randomized order at two inflation pressures, +20 or +30 cmH(2)O, and CC and CC/EEV were calculated from the plots obtained when the lungs were exsufflated to -20 cmH(2)O. (CC/EEV >1 indicates that airway closure might occur during tidal breathing). Furthermore, a measure of uneven ventilation, multiple breath alveolar mixing efficiency (MBAME), was obtained. RESULTS: Airway closure within the tidal volume (CC/EEV >1) was observed in four and eight children (not significant, NS) after 20 and 30 cmH(2)O inflation, respectively. However, CC(30)/EEV was >CC(20)/EEV in all children (P< or = 0.001). The MBAME was 75+/-7% (normal) and did not correlate with CC/EEV. CONCLUSION: Airway closure within tidal volumes may occur in artificially ventilated healthy children during ventilation with low inspiratory pressure. However, the risk of airway closure and thus opening within the tidal volume increases when the inspiratory pressures are increased.

Adolescent↗