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Biomedical subjects

A Larsson

Publications and source records attributed to A Larsson.

At least 235 records · Page 13Linked to original sources

Partial expression of GP Ib measured by flow cytometry in two patients with Bernard-Soulier syndrome.

Bernard-Soulier syndrome is a rare, congenital bleeding disorder caused by absent or defective GP Ib platelet membrane receptor for the von Willebrand factor (vWF). We studied two brothers with moderate bleeding symptoms. Bleeding time was prolonged and ristocetin-induced platelet aggregation was absent. Flow cytometric analysis showed that both boys had a subnormal expression of GP Ib. One antibody used (AN51) was bound only to 30% of the platelets and at a subnormal density. A second antibody (SZ2) also bound at a subnormal density but a normal fraction of the platelets were immunoreactive. Ristocetin stimulation of the patients' platelets in the presence of plasma resulted in a low binding of vWF, about 30% of healthy controls. On the other hand the expression of GP IIb/IIIa on the platelet membrane appeared to be supernormal even when the increased platelet size was taken into account as shown by the ratio between the density of GP IIIa and CD 9 structures. We conclude that these brothers have a variant of the Bernard-Soulier syndrome with a low expression of a GP Ib receptor.

Bernard-Soulier Syndrome↗

Prenatal diagnosis of glutathione synthase deficiency.

Prenatal diagnosis for glutathione synthase (EC 6.3.2.3) deficiency in two pregnancies of an at-risk couple was performed on amniotic fluid taken at 16 weeks' gestation. 5-Oxoproline (pyroglutamic acid) levels were 970 and 790 mumol/l compared with the normal mean value of 29 mumol/l (range 13-51 mumol/l). The pregnancies were terminated and the diagnosis in one case was subsequently confirmed by assay of glutathione synthase in cultured fetal fibroblasts. In the other, post-mortem tissue samples failed to grow.

Adult↗

Regional cerebral blood flow in normal pressure hydrocephalus: diagnostic and prognostic aspects.

Relative regional cerebral blood flow (rrCBF) was measured by single-photon emission tomography (SPET), using technetium-99m-d,l-hexamethylpropylene amine oxime (HMPAO) as flow tracer, in 23 patients with normal pressure hydrocephalus (NPH). 1000 MBq 99mTc-HMPAO was given intravenously and the rrCBF calculated as regional/cerebellar count level ratios. The patients were examined before and 3-12 months after ventriculoperitoneal shunt surgery. rrCBF was also determined in ten healthy aged matched volunteers who served as controls. The NPH patients had decreased rrCBF in the hippocampal regions and in the frontal and parietal white matter as compared to the controls. The frontal/parietal rrCBF ratio correlated with both psychiatric disability and the preoperative degree of incontinence. Decreased flow in frontal white matter, frontoparietal and hippocampal grey matter and a low frontalparietal grey matter flow ratio preoperatively correlated with improvement in both Mini Mental State score and psychiatric disability after shunt surgery. After shunt surgery the rrCBF increased in the mesencephalon, frontal grey and white matter, parietal white matter and hippocampus. The flow increase in hippocampal regions and frontal white matter correlated with improvement in psychiatric symptomatology. The results of this study regarding the frontal and hippocampal rrCBF patterns, and the clinical correlation, support the hypothesis that CBF changes in these regions are of pathophysiological and prognostic importance in NPH.

Adult↗

Presentation of the Plasmodium falciparum antigen Pf155/RESA to human T cells. Variations in responsiveness induced by antigen presenting cells from different but MHC class II identical donors.

The antibody response in humans naturally primed to a malaria vaccine candidate antigen (Pf155/RESA) is genetically regulated. Here, the impact of antigen presenting cells (APC) on the control of in vitro T-cell responses induced by Pf155/RESA or synthetic peptides corresponding to its major Pf155/RESA epitopes was studied. T cells and APC were from the peripheral blood of monozygotic or dizygotic twins and their age matched siblings, all living in the central highlands of Madagascar. When induced to proliferate (thymidine incorporation) in vitro by antigenic peptides, the T-cell responses varied less within the twin pairs than between them and their siblings or the entire group, implying that they were genetically regulated. Occasional MHC class II associations of some of the responses were weak and did not reflect underlying MHC class II restrictions. When T cells and APC from different but MHC class II identical donors were incubated in various combinations, antigen charged APC from homologous donors induced in vitro T-cell proliferation which differed from that induced by the T-cell donors' own APC. Pretreatment of the APC with either paraformaldehyde or anti-class II antibodies inhibited or abolished this antigen dependent T-cell proliferation. The results suggest that the observed differences in T-cell responses induced by APC from different donors reflect differences at the level of these cells. Whether they reflect differences in the proteases involved in antigen processing, in the costimulatory signals provided by the APC to the T cells or in the secretion of other regulatory factors remains to be elucidated.

Adolescent↗

Nitric oxide gives maximal response after coronary artery bypass surgery.

The dose-response to inhalation of nitric oxide (NO) after coronary artery bypass surgery was studied in seven patients with normal preoperative lung function and chest radiograms. During postoperative controlled ventilation with PEEP 5 and 10 cmH2O, the patients inhaled NO in concentrations of 2 to 25 ppm, in random order, for 6 to 10 minutes. Hemodynamic and oximetric data were analyzed before, 5 minutes after start of the NO inhalation, and 5 minutes after the cessation. The response was the same at all concentrations; mean pulmonary artery pressure decreased by 11 +/- 1% (P < 0.05) and pulmonary vascular resistance decreased by 22 +/- 2% (P < 0.05). Systemic hemodynamics did not change, but oximetric parameters tended to improve. Changes in PEEP did not affect the response. It is concluded that, in patients who have undergone coronary artery bypass grafting, inhalation of 2 to 25 ppm NO causes a dose-independent decrease in pulmonary artery pressure and pulmonary vascular resistance. In order to investigate the dose-response curve, concentrations lower than 2 ppm of NO must be used.

Aged↗

Histochemical visualization of mercury in the oral mucosa, salivary and lacrimal glands of BN rats with HgCl2-induced autoimmunity.

BN, but not LEW, rats treated with subcutaneous injections of mercuric chloride (HgCl2) develop an autoimmune syndrome with infiltration of mononuclear cells into various organs including the oral mucosa. In the present study, we have utilized autometallographic techniques to visualize mercury in the oral mucosa, salivary and lacrimal glands of mercury-sensitive BN and -non-sensitive LEW rats injected with HgCl2. Mercury was deposited intracellularly in dendritic cells that were scattered throughout the lamina propria and submucosal connective tissue of both rat strains. In addition, mercury was detected in dendritic cells appearing within small cell clusters in the juxtaepithelial connective tissue of BN oral mucosa. In salivary and lacrimal glands, mercury was found in dendritic cells scattered throughout the stroma as well as in mononuclear cell foci. Mercury was also found in ductal epithelium. No staining was seen in any of the non-mercury-treated controls. Phenotypic analysis revealed that most mercury-laden cells were ED2+ resident macrophages and that some, but not all, of these cells expressed MHC class II antigens (RT1B).

Animals↗

A new method for the relative quantification of rCBF examined by 99Tcm-HMPAO SPECT.

A new method for the analysis of regional cerebral blood flow (rCBF) studies, the 'Min-Max' method, was compared with the conventional method, the 'Average' method. Regional CBF was examined by single photon emission computed tomography (SPECT) using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO). The two methods were used to quantify the rCBF in a population of patients with various dementia disorders, and in healthy controls. Results from a phantom were also used. In the Average method the average counts per pixel (cp-1) within irregular manually drawn regions of interest (ROIs) was registered. In the Min-Max method the minimum cp-1 and maximum cp-1 within rectangular ROIs were registered for white and grey matter, respectively. The relative rCBF (rrCBF) was calculated as the ratio between the regional and cerebellar values. The Min-Max method gave systematically lower values for rrCBF in the white matter, in both clinical studies, and in the phantom, compared to the Average method. No difference was found in the grey matter results. The variability in rrCBF in the phantom study was greater with the Min-Max method than with the Average method, but this effect was counteracted in the clinical studies by a smaller interobserver error. The average regional differences between patients and controls appeared greater with the Min-Max method than with the Average method. The Min-Max method proved to be more simple to execute, involved a smaller observer error, and with respect to ability to distinguish patients with dementia disorders from controls, it appears to function at least as well as the accepted Average method.

Adult↗

Quantitative SPECT cisternography in normal pressure hydrocephalus.

Twenty-one patients with normal pressure hydrocephalus (NPH), 8 patients with various brain diseases with an element of hydrocephalus, and 7 patients with miscellaneous dementia disorders were investigated with quantitative radionuclide cisternography (RC) using single photon emission computerized tomography (SPECT). The total intracranial counts as well as the counts in the lateral and third ventricles were measured. All 15 NPH patients accessible for postoperative examination were improved after shunt surgery. In all groups the ventricular and total intracranial counts level increased during the measurement period but remained constant in distribution in each group. The NPH patients had a higher relative count value in the lateral and third ventricles compared to the patients with miscellaneous dementia disorders. The relative values in the third and lateral ventricles were predictive for the outcome of shunt surgery. Quantitative SPECT RC appears to be a useful diagnostic procedure in NPH investigations.

Adult↗

Contact stomatitis to mercury associated with spontaneous mononuclear cell infiltrates in brown Norway (BN) rats with HgCl2-induced autoimmunity.

Light microscopy and immunocytochemistry have been used to study the tissue reaction to non-irritant concentrations of mercury painted onto the oral mucosa of genetically mercury-sensitive BN rats. Low-dose skin injections of HgCl2 in BN rats result in an autoimmune syndrome, including also a spontaneous migration of T lymphocytes into the oral mucosa. Our results show that such infiltrates confer an increased degree of reactivity (contact stomatitis) to HgCl2 painted onto the BN (Hg) rat oral mucosa. In contrast, results were negative in the LEW rat strain, which is also resistant to development of autoimmunity to skin-injected mercury. The possible involvement of mucosal mercury-loaded macrophages is discussed. The results are also discussed with respect to possible etiologic and pathogenetic mechanisms involved in the development of dental material (amalgam)-associated lichenoid lesions of human oral mucosa.

Administration, Topical↗

Hg-provocation of oral mucosa in patients with oral lichenoid lesions.

Five amalgam-bearing patients, with clinically and histologically confirmed oral lichenoid lesions, were tested by applying 0.5% Hg in petrolatum for 10 min to clinically normal mucosa. Control sites were exposed to petrolatum only. Four amalgam-bearing patients with no clinical evidence of oral lichenoid lesions served as controls; they were subjected to similar Hg and petrolatum exposure. After 24 h, biopsies were taken and immunocytochemically analyzed with monoclonal antibodies to lymphoid and nonlymphoid cells. No distinct differences could be detected between the Hg-exposed areas of the lichen patients and those of the nonlichen patients. Furthermore, normal mucosa exposed to petrolatum only showed a staining pattern in the lichen patients which was no different from the nonlichen patients. The findings are discussed with respect to possible mechanisms of development of lichen-like lesions in oral mucosa.

Adult↗

The retrocuspid papilla and factor XIIIa: an epidemiologic and histomorphologic study.

The retrocuspid papilla (RCP) is a poorly recognized entity. In one part of our study, we found 10 cases of lesions clinically compatible with RCP in 1150 consecutively examined patients. In another part of the study, we found 15 cases of RCP in more than 2000 consecutive cases of oral mucosal hyperplasia submitted as surgical biopsies during 1989-92. The lesions were situated in the attached gingiva, lingual to the two mandibular canines, often bilaterally. They were covered by normal pink mucosa with a size and a height each of 2-3 mm. Histologically, the RCP was a broad-based, often downfolded hyperplasia, covered with a parakeratinized epithelium of normal thickness. The rete pegs were often elongated and blunt, frequently bent inward toward the center. The lamina propria was mostly composed of a loosely arranged, delicate, fibrous connective tissue. The lesions could be classified into two groups by the presence or absence of stellate and occasionally multinucleated fibroblasts. Immunohistochemical staining with an FXIIIa antibody disclosed a population of reactive spindle-shaped cells, mainly localized in the connective-tissue papillae. These cells may be of pathogenetic importance.

Adolescent↗

Pressure-volume relations of the respiratory system in healthy children.

Static pressure-volume (P-V) curves of the respiratory system were obtained in 48 healthy children (1 mo to 16 yr of age) during anesthesia and muscle paralysis. The lungs were inflated to a pressure of 25 to 40 cm H2O, and during the subsequent deflation an interrupter placed in the airway tubing opened and closed every 0.16 s. Airway flow was integrated to obtain the volume decrement between consecutive flow interruptions. Airway pressure was measured during interruptions, and a curve relating pressure to lung volume was plotted, assuming the lung volume at zero pressure to equal functional residual capacity (FRC). FRC was measured using tracer gas washout. The maximum slope of the P-V curve (maximum compliance = Crsmax, ml/cm H2O) was closely related to length (in centimeters) of the child: Crsmax = 7.7 x 10(-4) x length2.38; r = 0.97. The pressure coinciding with Crsmax was 6 +/- 1 cm H2O (mean +/- SD) in infants (1 to 6 mo of age) and 12 +/- 1 cm H2O in older children (> 1.5 yr of age). Total lung capacity (TLC) per kg body weight increased with age and was 52 +/- 13 ml/kg in infants and 87 +/- 11 mg/kg in older children. The FRC/TLC ratio was greater in infants (38 +/- 4%) than in older children (30 +/- 5%). The lung volume coinciding with Crsmax was nearly the same at all ages, when expressed as a percentage of TLC: 62 +/- 3%. Specific compliance of the respiratory system, that is, Crsmax/TLC, decreased with growth and was 0.044 +/- 0.006 cm H2O-1 in infants and 0.035 +/- 0.004 cm H2O-1 in older children. It is concluded that although the P-V relations of the respiratory system changed markedly with growth, especially during the first year of life, the lung volume (%TLC) at which maximum compliance occurred varied little.

Adolescent↗

Lactate release from the subcutaneous tissue in lean and obese men.

Lactate concentration in the subcutaneous interstitial fluid and adipose tissue blood flow (ATBF, ml/100 g.min) were simultaneously measured with the microdialysis technique combined with 133Xe clearance in the abdominal and femoral subcutaneous adipose tissue in nine lean and nine obese men. The studies were performed both in the postabsorptive state and 2 h after an oral glucose load and the results compared to the lactate levels in arterialized venous plasma. After an overnight's fast, arterial lactate was 738 +/- 49 and 894 +/- 69 microM (mean +/- SE) (P < 0.05) in the lean and obese subjects, respectively. The interstitial lactate levels were significantly higher than blood lactate in both subject groups without any regional differences. Abdominal and femoral ATBF was 3.2 +/- 0.6 vs. 2.8 +/- 0.4 and 1.7 +/- 0.3 vs. 2.4 +/- 0.4 ml/100 g.min (P < 0.05) in lean and obese subjects, respectively. Mean apparent lactate release from the abdominal vs. femoral adipose tissue in the fasting state was 10.5 +/- 3.1 vs. 8.6 +/- 2.3 and 6.0 +/- 2.3 vs. 8.5 +/- 2.3 mumol/kg.min (NS) in lean and obese subjects, respectively. Both plasma and interstitial lactate levels increased significantly after an oral glucose load in both subject groups. However, apparent lactate release increased significantly only in the lean group. It is concluded that subcutaneous adipose tissue is a significant source of whole-body lactate release in the postabsorptive state and that this is further enhanced in obese subjects due to their large adipose mass.

Abdomen↗

Impaired synthesis of lipoxygenase products in glutathione synthetase deficiency.

Glutathione synthetase deficiency (GSD) is an inborn error of glutathione (GSH) metabolism leading to a generalized intracellular GSH deficiency. Because GSH is required for leukotriene C4 (LTC4) synthesis, we studied synthesis and metabolism of several lipoxygenase products in two patients with GSD by radio-HPLC, UV spectrophotometry, and enzyme immunoassays. In both patients, LTC4 synthesis was significantly decreased in calcium ionophore-stimulated neutrophils (up to 0.4 ng/10(6) cells; controls, 5.0 +/- 0.9) and monocytes (up to 3.6 ng/10(6) cells; controls, 30.2 +/- 3.3). LTB4 synthesis was about seven times higher in GSD cells compared with controls, whereas synthesis of other 5-, 12-, and 15-lipoxygenase products and prostaglandin E2 was not affected. Neutrophils and monocytes from both patients showed a marked reduction in capacity to form [3H]LTC4 from [3H]LTA4 (9-14% of control values). Urinary LTE4 was finally found to be 50-fold lower in GSD, reflecting a decreased synthesis of cysteinyl LT in vivo. GSD may serve as a unique model for the linkage between LT synthesis and GSH metabolism in vivo.

Calcimycin↗

Allergic and irritant contact responses to DNFB in BN and LEW rat strains with different TH1/TH2 profiles.

BN and LEW rats possess different and extreme profiles of TH1/TH2 cells. The main objective of this study was to determine if this constitutively expressed property may influence the propensity to develop contact allergy to a potent contact sensitizer, 2,4-dinitro-1-fluorobenzene (DNFB). In order to avoid overlapping reactions due to toxicity, we defined non-irritant threshold levels of DNFB histologically in ear skin, dorsal skin and oral mucosa prior to the sensitization experiments. Evaluation of the elicitation response was carried out by an invasive method (biopsy). LEW rats proved to express a more extensive challenge response to DNFB than rats of the BN strain. Further, epicutaneous sensitization with DNFB gave a better challenge response than the subcutaneous route regardless of rat strain. In ear skin, but not in oral mucosa, the response was more vigorous after five than after two exposures. Our results are discussed with respect to the possibility that the TH1 type cells may play a significant role in the development of experimental contact allergy.

Animals↗

The histological and immunohistochemical pattern of positive patch test reactions to gold sodium thiosulfate.

Gold sodium thiosulfate, inserted in the patch test standard series, gives a surprisingly high yield of positive reactions, about 10% of tested eczema patients, but with a low degree of clinical relevance. A histopathological study on patch test reactions was carried out in patients selected because of a combined contact allergy to gold sodium thiosulfate and nickel. Biopsies were taken from macroscopically similar reactions in dilution series of each allergen. The histological picture was clearly eczematous, without irritative features. In a blind comparison, test reactions induced by the two allergens could not be differentiated from each other. Long-lasting patch test reactions to gold sodium thiosulfate were characterized by an intense lymphocytic dermal infiltrate without epidermal involvement. Immunohistochemically, CD4+ and CD8+ T lymphocytes could be detected already 4-8 h post-challenge, and "naive" as well as "memory"-type T cells were demonstrated. Apparently, our findings reflect a true contact allergy to gold sodium thiosulfate.

Adult↗