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Biomedical subjects

A Carlström

Publications and source records attributed to A Carlström.

At least 19 recordsLinked to original sources

Effect of a new international reference preparation for proteins in human serum (certified reference material 470) on results of the College of American Pathologists Surveys for plasma proteins.

OBJECTIVE: To examine the impact of a new international reference preparation for serum proteins on the among-manufacturer variance in the College of American Pathologists Surveys. DATA SOURCE: The results of the Surveys for the years 1993-1998, supplied by the College of American Pathologists. DATA EXTRACTION AND SYNTHESIS: Mean values for manufacturers' assays were compared for each protein in the quality control samples. Results were separated by the reported reference material from which values for calibrators had been transferred. Standard statistical parameters (means, standard deviations, and coefficients of variation) were calculated from the reported means. CONCLUSIONS: Among-manufacturer coefficients of variation have dropped significantly for most serum proteins since the introduction of the new reference material. Possible reasons for continued differences are discussed.

Albumins↗

Consensus of a group of professional societies and diagnostic companies on guidelines for interim reference ranges for 14 proteins in serum based on the standardization against the IFCC/BCR/CAP Reference Material (CRM 470). International Federation of Clinical Chemistry. Community Bureau of Reference of the Commission of the European Communities. College of American Pathologists.

The release in 1993 of a new reference material for serum proteins, CRM 470/RPPHS 5 has given rise to a great improvement in the between-laboratory variability of serum protein measurements worldwide. Conversion to the new reference material results in significant changes in reference values for some proteins. The establishment of new reference ranges will take a considerable time, and in the interim several professional societies and diagnostic companies have agreed to use consensus reference ranges based on studies already undertaken.

Blood Proteins↗

Serum levels of androgens and estrogens and 'steroid-sensitive' liver proteins in early human pregnancy: influence on the gender of the offspring.

Serum androgens, estrogens, 'steroid-sensitive proteins', thyroid components, and albumin were measured twice within a 4-5 week interval in 44 cases of early normal pregnancy (gestational weeks 8-18). Positive correlations were found in the total material between dehydroepiandrosterone sulfate (DHAS) and testosterone (T), unconjugated and total estrone, albumin, tetraiodothyronine, and calculated free tetraiodothyronine concentrations and within 2-week intervals between DHAS and T, estradiol-17 beta, and unconjugated and total estrone, and between T and estradiol-17 beta and unconjugated estrone. Positive correlations were also found between the rates of change in DHAS of albumin. No significant association was found between 'steroid-sensitive proteins' and androgens or androgen/estrogen ratios. Women giving birth to girls had significantly higher serum levels of pregnancy-associated alpha 2-macroglobulin, thyroxine-binding globulin, and ceruloplasmin and lower ratios between T and sex hormone binding globulin than women giving birth to boys. The important role of placental aromatization in the metabolism of maternal androgens is well known. Albumin binding and thyroid status may also affect the metabolism of DHAS during pregnancy. The androgen/estrogen balance may be of little importance for the regulation of 'steroid-sensitive' proteins during early pregnancy. The mechanism behind the higher serum levels of pregnancy-associated alpha 2-macroglobulin, thyroxine-binding globulin, and ceruloplasmin in women giving birth to girls remains to be elucidated.

Adult↗

Diagnostic and prognostic value of interleukin-6 and C-reactive protein in community-acquired pneumonia.

The diagnostic and prognostic value of admission serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) was investigated in 203 hospital-treated patients with community-acquired pneumonia (CAP). In serum samples obtained during the first 24 h after admission, IL-6 was detectable in 198 patients (98%), with a median value of 50 ng/l. Ten % of the patients had IL-6 values of 1000 ng/l. A clear positive correlation between IL-6 and CRP was found (r = 0.29, p < 0.0001). Patients with high IL-6 or CRP levels had longer duration of fever, longer hospital stay, and had less often recovered clinically or radiographically on follow-up weeks after discharge. A high IL-6, but not a high CRP, also seemed to be associated with a higher mortality. Bacteremic pneumococcal pneumonia had the highest levels of IL-6 (mean 2852 and median 420 ng/l) and CRP (mean 292 and median 285 mg/l). High IL-6 values were also seen in patients with non-bacteremic pneumococcal pneumonia, while all patients with pneumonia due to other bacterial, or viral, aetiology had IL-6 levels of < or = 300 ng/l. In conclusion, IL-6 and CRP are promising diagnostic and prognostic tools in the management of CAP. Further studies are needed to establish the usefulness of repeated measurements early in the hospital course of the disease.

Bacteremia↗

The diagnostic value of repetitive preoperative analyses of C-reactive protein and total leucocyte count in patients with suspected acute appendicitis.

BACKGROUND: Studies have shown that C-reactive protein (CRP) and total leucocyte count (WBC) in suspected acute appendicitis analysed only on admission gave valuable information to guide the surgeon. The aim of this study was to investigate the usefulness of CRP and WBC measured repetitively before operation. METHODS: During a 1-year period 227 patients were studied before emergency appendicectomy. CRP and WBC were analysed every 4th h. The upper limits of the reference intervals used were 9.0 x 10(9)/l for WBC and 10 mg/l for CRP. RESULTS: Of the 227 appendicectomized patients, 170 (75%) had acute appendicitis. Sixty-six of the patients were tested on two or more occasions every 4th h. Forty-six of these patients had appendicitis; repetitive tests showed a continuing rise in CRP values but a continuing decrease in WBC. The negative appendicectomy rate among these 66 patients was 30%, which theoretically would have fallen to 19% if patients with normal results had not been subjected to surgery. CONCLUSIONS: Repeated laboratory tests for CRP and WBC should be performed in patients with suspected acute appendicitis requested to stay for further observation. If these test results are normal, the surgeon should preferably refrain from operating but consider other differential diagnoses.

Acute Disease↗

Transthyretin messenger ribonucleic acid expression in the pancreas and in endocrine tumors of the pancreas and gut.

Transthyretin (TTR) cDNA probes were used to determine the presence of TTR mRNA in Northern blots from rat, porcine, and human organs as well as from human endocrine tumors. We also used in vitro translation in our study of the human tissues. In accordance with previous findings, TTR mRNA was found in the choroid plexus and, to a lesser extent, in the liver of all three species. In addition low levels of TTR mRNA were identified in the rat and human pancreas. All of the endocrine pancreatic tumors (two glucagonomas, two insulinomas, and one nonfunctional tumor) and the gut carcinoid also contained TTR mRNA, whereas other endocrine tumors (two pheochromocytomas and one paraganglioma) and one adenocarcinoma of the pancreas were TTR mRNA negative. The level of TTR mRNA expression in most of the endocrine pancreatic tumors exceeded that in the liver. The in vitro translations produced pre-TTR molecules of similar size for all TTR mRNA-positive human organs and tumors.

Animals↗

Transthyretin microheterogeneity and thyroxine binding are influenced by non-amino acid components and glutathione constituents.

Two non-amino acid components as well as the glutathione constituents in labile associations with transthyretin (TTR) have been detected by preparative polyacrylamide gel electrophoresis from preparations isolated by affinity chromatography on Sepharose-bound retinol-binding protein (RBP). Incubation of native or reduced TTR with these novel components influenced the quaternary structure and caused reactions with reduced TTR in particular. Reduction of isolated TTR monomers released cysteine from the quantitatively major monomer, but non-amino-acid components from another dominating monomer. The reaction patterns also influence thyroxine (T4) binding. These relationships indicate that interactions in serum of TTR with constituents of glutathione and components different from T4 and retinol-RBP are important for the metabolism and function of TTR.

Chromatography, Affinity↗

Transthyretin immunoreactivity in human and porcine liver, choroid plexus, and pancreatic islets.

We examined transthyretin immunoreactivity (TTR-IR) in human and porcine liver, choroid plexus, and pancreatic islets with both polyclonal and monoclonal antibodies to TTR. The specificity of the immunoreactions and the effects of various fixatives were tested in immunohistochemical and dot-blot systems. B-5 fixative (mercuric chloride and sodium acetate in formalin) was the best immunopreservative. In both species, the TTR-IR in choroid plexus epithelial cells was strong and was much greater than that in hepatocytes. Glucagon cells in pancreatic islets were also strongly TTR immunoreactive. Insulin cells were slightly TTR immunoreactive in human but strongly so in porcine pancreas. The finding of TTR-IR in normal islets explains the presence of TTR-IR in human endocrine pancreatic tumors, notably glucagonomas and malignant insulinomas.

Animals↗

Transthyretin in endocrine pancreatic tumors.

The occurrence of transthyretin (TTR) in 25 endocrine pancreatic tumors was investigated by immunohistochemical methods using both polyclonal and monoclonal antibodies. All malignant insulinomas were strongly TTR immunoreactive, more so than their benign counterparts, which in some cases were TTR negative. All glucagonomas and nonfunctioning tumors were TTR immunoreactive, whereas gastrinomas and VIPomas were TTR negative. TTR, chromogranin A, and the argyrophil reaction (Grimelius' silver technique) had similar distributions among the cells in many, but not all, tumors. Coexistence of TTR with glucagon, insulin, or pancreatic polypeptide in tumor cells was demonstrated. TTR was also quantitated in preoperative serum samples by electroimmuno assay in some cases. Although one patient with a glucagonoma had a markedly increased serum TTR level, five other patients with endocrine tumors, including two patients with glucagonoma, had TTR levels in serum that were within or below the reference range.

Adenoma, Islet Cell↗

Serum levels of estrogens and of five 'steroid sensitive' proteins in early normal pregnancy.

Serum concentrations of sex hormone binding globulin (SHBG), pregnancy associated alpha 2-glycoprotein (alpha 2-PAG), caeruloplasmin (Cp), alpha 1-antitrypsin (alpha 1-At) and transferrin (Tf), unconjugated and total estrone, and unconjugated estradiol-17 beta were measured twice at a 4-5 week interval in 43 cases of early normal pregnancy (gestational weeks 6-19). Significant correlations between estrogen and protein levels in the total material were observed for all proteins except for Tf. However, within 2-week intervals of pregnancy, significant correlations were obtained only in certain intervals between estrogens on one hand and SHBG, Cp and alpha 1-At on the other. Significant correlations between rates of increase of estrogens and of proteins were obtained only at certain occasions for SHBG, Cp, Tf and alpha 1-At. The results indicate that, although estrogens may have a modulatory function in 'steroid-sensitive' protein synthesis, they are probably not the main physiological regulator.

Ceruloplasmin↗

Different types of microheterogeneity of human thyroxine-binding prealbumin.

Human thyroxine-binding prealbumin or transthyretin has been isolated by three different methods. In all cases, the isolated material is microheterogeneous in an isoelectric focusing system, revealing a pattern of at least 10 bands. These subforms represent tetramers. Dissociation of the protein in serum samples and dissociation in the presence of urea or sodium dodecyl sulfate (SDS) reveal eight other forms, differing in isoelectric point and concluded to be monomers. Two different sets of dissociated forms are identified, one from urea treatment and the other from SDS treatment. The latter set is apparently also present in serum. Interpretations are complicated by multiplicities of all forms, atypical electrophoretic migrations, nonidentical effects of urea and SDS, and the absence of dimer under most conditions. However, reassociations of monomers and formation of interspecies hybrid molecules identify dimers and clarify interpretations of the dissociated sets. In at least five of the forms likely to represent monomers, the difference is dependent on the nature of the SH group at Cys-10, which can be oxidized, can be reduced, or can be in a mixed disulfide, probably with glutathione and its degradation products. Amino acid sequence analysis reveals an additional N-terminal heterogeneity (with start at positions 1, 2, and 3) of the three most abundant monomers, but this does not explain the observed differences among monomeric forms. It is concluded that prealbumin exhibits different types of microheterogeneity, the major pattern of which is explained by the status of the subunit SH group and the ability of prealbumin to dissociate into monomers. A relation appears to exist between SH group status on the one hand, and retinol-binding protein interaction, the ability to dissociate into monomers, and possibly also binding of thyroxine on the other. These interactions suggest complex functional relationships for prealbumin in serum.

Amino Acid Sequence↗

Clinical manifestations of Borrelia infections of the nervous system.

Clinical, treatment and laboratory parameters were analyzed in 46 consecutive Swedish patients with Borrelia infections of the nervous system. The importance of age in the clinical symptoms, the wide spectrum of disease, and the chronic behaviour of the Borrelia infection of the nervous system was stressed, as well as the benefit of high-dose intravenous antibiotics, especially penicillin G. Borrelia infection of the nervous system can imitate other diseases. When associated with meningitis it can mimic psychosomatic disorders, when associated with radiculoneuritis it may imitate herniated discs and when central nervous involvement of the Borrelia infection occurs, it can mimic a non-infectious, thrombotic or haemorrhagic cerebro-vascular disease.

Adolescent↗

Oestrogen and thyroxine-binding globulin levels in early normal pregnancy.

Peripheral serum levels of thyroxine-binding globulin (TBG), unconjugated and total oestrone, and unconjugated oestradiol-17 beta were measured twice in 60 cases of early normal pregnancy (gestational weeks 6-19). Although highly significant correlations between TBG and oestrogen levels were obtained in the total material, the correlations within two-week intervals of pregnancy were rather poor and mostly insignificant. Furthermore, there were no associations at all between the increase rates of TBG and those of the oestrogens, either within two-week intervals or in the total material. The findings do not support the common concept of continuously rising oestrogen stimulation as the main factor affecting the TBG synthesis during pregnancy.

Estradiol↗

Thyroxine-binding globulin in spontaneous abortion.

Thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), thyroxine (T4), free T4, triiodothyronine (T3) and thyroid-stimulating hormone (TSH) were studied in 144 apparently healthy, euthyroid pregnant women displaying miscarriages. In an additional group of 18 aborting women a frozen blood sample drawn in early pregnancy was similarly analyzed for the thyroid components as well as for human chorionic gonadotropin (HCG). The values were compared to those of normal pregnancies (n = 228) at corresponding intervals. Significantly lower values of TBG were found in the spontaneously aborting group. A significantly lower value of TBG was found to be more predictive concerning spontaneous abortion than that of HCG.

Abortion, Spontaneous↗

Monoclonal antibodies to transthyretin.

Monoclonal antibodies (mabs) have been raised against human transthyretin (hTTR). The protein was isolated by an affinity chromatography procedure using Sepharose-hRBP and BALB/c mice were immunized. Following fusion with SP 2/0 myeloma cells, 26 single cell clones producing antibodies against hTTR were isolated. These mabs have been characterized and efforts have been made to establish the epitopes that they recognize. So far at least two different epitopes have been identified both residing in a mid-region fragment corresponding to the amino acid sequence 35-103 of the hTTR subunit. All mabs have been found suitable for immunohistochemical localization of hTTR even in formaldehyde fixed and paraffin embedded tissues.

Animals↗

Thyroid hormone binding in serum of 15 vertebrate species: isolation of thyroxine-binding globulin and prealbumin analogs.

The binding of [125I]T4 to serum proteins was studied in human, monkey, cattle, sheep, goat, water buffalo, horse, swine, dog, cat, rabbit, rat, chicken, frog, and salmon. Attempts were made to isolate thyroxine-binding globulin (TBG) and thyroxine-binding prealbumin (TBPA) from serum of all species, utilizing purification methods based on the specific properties of these proteins. TBPA was found to exist in all species examined. The protein was found anodal to albumin only in human, monkey, horse, and chicken. In cattle, swine, dog, cat, rabbit, frog, and salmon, TBPA was found cathodal to albumin, while sheep, goat, water buffalo, and rat had identical mobility of albumin and TBPA. The presence of TBG was demonstrated in larger mammals. In cat, rabbit, rat, chicken, frog, and salmon, TBG could not be demonstrated. The thyroxine-binding capacity of TBPA in serum varied from 1000 to greater than 6000 nmol/l and that of TBG between 150 and 600 nmol/l. TBPA from all species except salmon showed affinity to human retinol-binding protein. The presence of TBPA in all vertebrates suggests prealbumin to be a far more important thyroxine carrier than earlier anticipated.

Animals↗

Genetics and clinical significance of thyroxine binding globulin deficiency, an analysis of seven families.

Seven families, ascertained through probands with undetectable levels of thyroxine binding globulin (TBG) were studied from clinical and genetic points of view. The blood levels of TBG, thyroxine binding prealbumin (TBPA), thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4) were determined in altogether 128 family members. The concentration of free thyroxine (FT4) was calculated from the concentrations of T4, TBG and TBPA. Only men (n = 15) were found to have total TBG deficiency. Their TSH levels were within normal range and they did not show any clinical symptoms of thyroid dysfunction. The mothers and daughters of the affected men had significantly lower TBG levels than control women. Segregation analysis performed on 46 nuclear families showed significant evidence for an X-linked additive mode of transmission and an additional multifactorial component with heritability 0.47.

Adolescent↗

Chronic meningitis caused by a penicillin-sensitive microorganism?

21 patients studied had persistent or progressive chronic meningitis not associated with a demonstrable infectious or other disease, except Streptococcus milleri antigen in the cerebrospinal fluid of 1 patient. The cerebrospinal-fluid (CSF) abnormalities consisted of a moderate, predominantly mononuclear, pleocytosis, a sharp rise in CSF protein (mean 2.3 g/l), intrathecal synthesis of considerable quantities of oligoclonal immunoglobulin G, and, in half the patients, a fall in the CSF-glucose/blood-glucose ratio. In all patients symptoms began during summer or autumn. In 4 patients the onset was preceded by localised cutaneous lesion, described as erythema chronicum migrans. 4 more patients had been bitten by ticks in the weeks before onset of symptoms. The patients had profound fatigue, malaise, and weight-loss. Half had fever, usually moderate. The neurological abnormalities included aseptic meningitis, cranial neuropathy (mostly facial-nerve paralysis), motor and sensory peripheral radiculoneuropathy, and myelitis. The patients improved or recovered, sometimes dramatically, during a 2-week course of intravenous penicillin G.

Adolescent↗