Biomedical subjects

S Krantz

Publications and source records attributed to S Krantz.

At least 19 recordsLinked to original sources

PubMed2006

Anemia in the elderly-clinical findings and impact on health.

Anemia is common in older people and it becomes more so with advancing decades. Because the older population is increasing, the prevalence of anemia and consequently its impact on health and healthcare expenditure is expected to rise. Although the causes and consequences of anemia have not been fully elucidated and its etiology is occasionally elusive, clinical evidence has indicated that anemia itself is a cause of morbidity and it can complicate other health conditions. The clinical approach to anemia is evolving. In the past, anemia was mainly seen as a sign of underlying disease; today, anemia is considered to be a cause of severe deterioration of quality of life, morbidity, and decline in physical function, and a risk factor for death. A better understanding of anemia in the elderly will lead to improved treatment strategies, including the more judicious use of transfusion and appropriate use of erythropoietic agents.

Aged↗

PubMed2001

Binding of Amadori glucose-modified albumin by the monocytic cell line MonoMac 6 activates protein kinase C epsilon protein tyrosine kinases and the transcription factors AP-1 and NF-kappaB.

An affinity purification procedure is employed for the isolation of FL-specific binding proteins from MM6 cell membranes using magnetobeads coated with glycated polylysine and elution with FL and glycated 6-aminocaproic acid. Two main binding proteins were identified as membrane-bound nucleolin and cellular myosin heavy chain, which are glycosylated. This study shows that in these cells binding of short-term glycated albumin leads to activation of PKC, especially its isoform epsilon and this is linked to translocation of AP-1 and NF-kappaB into the nucleus. Consequently, an increased formation of IL-1ss mRNA is observed. The PKC inhibitor GO6976 prevents all these effects. Glycated albumin also stimulates activation of PTK. The PTK inhibitor genistein prevents activation of AP-1 indicating that PTK is also involved in this process, whereas NF-kappaB translocation is only dependent on PKC activation.

Carrier Proteins↗

PubMed2000

Purification and characterization of a 200 kDa fructosyllysine-specific binding protein from cell membranes of U937 cells.

Amadori-modified proteins are bound by macrophages and monocytes via fructosyllysine-specific receptors. Detergent extracts from U937 cell membranes were used to purify the binding proteins by affinity purification on glycated polylysine coated magnetic beads followed by SDS-PAGE. Two proteins of 200 and 100kDa were isolated. MS-analysis of the 200 kDa protein showed high homologies with cellular myosin heavy chain, type A. Both fructosyllysine specific binding proteins, cellular myosin heavy chain and nucleolin, are glycosylated.

Amino Acid Sequence↗

PubMed1999

Flow cytometric analysis of in vitro proinflammatory cytokine secretion in peripheral blood from multiple sclerosis patients.

The cytokines, interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-2 (IL-2) are important endogenous proinflammatory proteins and have been linked to disease activity in multiple sclerosis. In this study, we use flow cytometric methodology to compare the secretion of IFN-gamma, IL-2, and TNF-alpha from peripheral blood-derived T cells of multiple sclerosis patients to the secretion in healthy controls. The percentages of IFN-gamma, IL-2, and TNF-alpha secreting cells are not significantly different between multiple sclerosis patients and controls. However, the TNF-alpha secreting CD3 cell percentage is correlated with the IFN-gamma and IL-2 secreting CD3 cell percentages in multiple sclerosis patients. In the controls, only the TNF-alpha secreting CD3 cell percentage is correlated with IFN-gamma. These findings show that correlated secretion of cytokines occurs in multiple sclerosis and suggest that concerted intercytokine interactions may play an important role in the disease.

Adolescent↗

PubMed1998

A new whole-body exposure chamber for human skin and lung challenge experiments--the generation of wheat flour aerosols.

A new whole-body exposure chamber for human skin and lung challenge offers possibilities for experimental exposure challenges carried out in clinical practice, for exposure of patients, in research and for investigations of the effects of exposure on the skin and in the respiratory tract. The chamber system can be used for both aerosols and gases. Dynamically controlled, the chamber is relatively easy to operate and to clean. Air exchange rates can be varied between 6-12/h. Initial studies with wheat flour have been carried out. The homogeneity and stability of the wheat flour aerosol concentration (the spatial and the temporal variation) inside the chamber can be kept at acceptable levels.

Administration, Cutaneous↗

PubMed1997

Assessment of past exposure to man-made vitreous fibers in the Swedish prefabricated house industry.

Large quantities of man-made vitreous fibers (MMVF) are handled in the Swedish prefabricated wooden house industry. The present study is part of a program to investigate mortality, cancer incidence, and current as well as previous exposure to MMVF among workers in the Swedish prefabricated wooden house industry. Since measurements of historical fiber exposure levels are lacking, these were calculated by the application of a matrix of multipliers to recently measured MMVF levels. The multipliers represented changes over time in production rate, technical properties of the fibers, manual handling vs. automation, and ventilation control. The multipliers were based on a similar matrix, developed for the MMVF-manufacturing industry, which was modified to reflect the conditions in the wooden house industry. The model was developed for the highest-exposed job title in the study, insulators. One hundred and twenty samples of airborne fiber were taken in 11 plants to reflect current exposure levels. The highest mean fiber exposure level for insulators was assessed as 0.18 f/ml (geometric mean), which occurred during the mid-1970s, compared to 0.10 f/ml at the end of the 1980s and the early 1960s. Changes in production rate, improved ventilation control, and the surface area of the total amount of MMVF sheets handled per insulator were the most important variables of the model. No increased risk of lung cancer was found in the present industry.

Air Pollutants, Occupational↗

PubMed1997

Erythroid response to treatment with G-CSF plus erythropoietin for the anaemia of patients with myelodysplastic syndromes: proposal for a predictive model.

Previous studies have shown that approximately 40% of patients with myelodysplastic syndrome (MDS) and anaemia respond to treatment with human recombinant granulocyte-CSF (G-CSF) plus erythropoietin (epo). The present study was designed to investigate pre-treatment variables for their ability to predict erythroid responses to this treatment. 98 patients with MDS (30 RA, 31 RARS, 32 RAEB, five RAEB-t) were treated with a combination of G-CSF (0.3-3.0 microg/kg/d, s.c.) and epo (60-300 U/kg/d, s.c.) for at least 10 weeks. Minimum criteria for erythroid response was a 100% reduction of red blood cell (RBC) transfusion need or an increase in haemoglobin level of > or = 1.5 g/dl. 35 patients (36%) showed responses to treatment. Medium duration of response was 11-24 months. In multivariate analysis, serum erythropoietin levels and initial RBC-transfusion need retained high statistical significance (P < 0.01). Using pre-treatment serum epo levels as a ternary variable (< 100, 100-500 or > 500 U/l) and RBC transfusion need as a binary variable (< 2 or > or = 2 units per month), the analysis provided a predictive score for erythroid response. This score divided patients into three groups: one group with a high probability of erythroid responses (74%), one intermediate group (23%) and one group with poor responses to treatment (7%). This predictive scoring system could be used in decisions regarding use of these cytokines for treating the anaemia of MDS, both for defining patients who should not be given the treatment and for selecting patients for inclusion in prospective trials.

Aged↗

PubMed1997

Evidence for binding of in vitro glycated low-density lipoproteins by fructosyllysine-specific sites on macrophages and U937 monocyte-like cells.

Early development of arteriosclerosis is a main late complication of diabetes mellitus. Although its uptake by LDL receptors is impaired, glycated LDL is thought to play a role in foam cell formation from macrophages. In the present study we show binding of glycated LDL (8-9 mol fructosyllsine/mol apo B) to macrophages and to the monocyte-like cell line U937. The binding involves fructosyllysine-specific binding sites, as well as LDL and scavenger receptors. Fructosyllysine and glycated albumin were competitors for binding of 125I-labelled glycated LDL by macrophages and U937 cells. Scatchard analysis of binding data using a two ligands binding model showed a linear plot with Ka = 2.6 x 10(7) M-1 for U937 cells, which lack scavenger receptors. On U937 cells only the 200 kDa fructosyllysine-specific receptor protein and the 165 kDa LDL receptor were involved in binding glycated LDL as evidenced by ligand blotting. U937 cell uptake and degradation of glycated LDL was mediated by fructosyllysine-specific and LDL receptors. Binding of glycated LDL by macrophages via fructosyllysine-specific sites could be demonstrated in only 6 from 35 rats investigated, indicating that the receptor is not expressed in each individual. Whether the fructosyllysine-specific receptor mediated pathway is relevant for uptake and degradation of glycated LDL in vivo is yet to be determined.

Animals↗

PubMed1996

Preliminary data on hard metal workers exposure to tungsten oxide fibres.

The first personal exposure data for tungsten oxide fibres, in two hard metal manufacturing industries is presented. Occupational exposure was studied by static and personal measurements during tungsten metal production. Three different initial materials were used, ammonium-paratungstate (APT), blue oxide and tungsten trioxide. In both factories, airborne tungsten oxide fibres were detected both in static and personal samples. Fibre exposure varies for different activities. Charging of raw material, changing the hammer, cleaning-work on the cyclone and the micro-filter were found to be among the most high dusty operations. However, as workers use respirators during cleaning operations, these filters could not be related to personal exposure. The calcination of APT to the blue oxide generates fibrous dust. The raw material imported as blue oxide is also fibrous material and both charging it into the calcination furnace and re-charging it into the reduction furnace generates unnecessarily additional dusty periods. A single reduction-stage is, therefore, preferable. Furthermore, the tungsten trioxide raw material is non-fibrous, therefore, calcination of APT to tungsten trioxide and its reduction to tungsten metal is preferable with respect to minimising workers exposure to tungsten oxide fibres.

Air Pollutants, Occupational↗

PubMed1996

Maintenance treatment of the anemia of myelodysplastic syndromes with recombinant human granulocyte colony-stimulating factor and erythropoietin: evidence for in vivo synergy.

Patients with myelodysplastic syndromes (MDS) have refractory cytopenias leading to transfusion requirements and infectious complications. In vitro marrow culture data have indicated that granulocyte colony stimulating factor (G-CSF) synergizes with erythropoietin (EPO) for the production of erythroid precursors. In an effort to treat the anemia and neutropenia in this disorder, MDS patients were treated with a combination of recombinant human EPO and recombinant human G-CSF. Fifty-five patients were enrolled in the study of which 53 (96%) had a neutrophil response. Forty-four patients were evaluable for an erythroid response of which 21 (48%) responded. An erythroid response was significantly more likely in those patients with relatively low serum EPO levels, higher absolute basal reticulocyte counts and normal cytogenetics at study entry. Seventeen (81%) of the patients who responded to combined G-CSF plus EPO therapy continued to respond during an 8-week maintenance phase. G-CSF was then discontinued and all patients' neutrophil responses were diminished, whereas 8 continued to have an erythroid response to EPO alone. In 7 of the remaining 9 patients, resumption of G-CSF was required for recurrent erythroid responses. The median duration of erythroid responses to these cytokines was 11 months, with 6 patients having relatively prolonged and durable responses for 15 to 36 months. Our results also indicate that approximately one half of responding patients require both G-CSF and EPO to maintain an effective erythroid response, suggesting that synergy between G-CSF and EPO exists in vivo for the production of red blood cells in MDS.

Adult↗

PubMed1996

Differential expression of fructosyllysine-specific receptors on monocytes and macrophages and possible pathophysiological significance.

A differing individual expression of fructosyllysine-specific receptors has been found on the monocytes of 90 insulin-dependent diabetic patients and 101 healthy control subjects. The degree of receptor expression is neither age- nor sex-dependent; however, in the diabetic group it correlates significantly with the severity and age of onset of diabetic microangiopathy. To interpret the results of the human study, spontaneously diabetic and non-diabetic BB/OK rats were used to estimate tissue content of glucose-modified proteins and capillary basement membrane thickness in relation to the receptor expression on macrophages. In non-diabetic and diabetic rats no correlation was found between receptor expression and tissue content (i.e. artery, nerve) of fructosyllsine and fluorescent advanced glycation end products. However, animals which express the fructosyllysine receptor showed a greater increase in muscle capillary basement membrane thickness. There are indications that fructosyllysine receptor expression is positively associated with indices of diabetic complications such as microangiopathy and/or capillary basement membrane thickening.

Adult↗

PubMed1996

The value of clinical judgment in the diagnosis of nosocomial pneumonia.

BACKGROUND: Nosocomial pneumonia presents a diagnostic and therapeutic challenge in the care of critically ill patients. The present study was designed to determine as closely as possible the occurrence of nosocomial pneumonia in surgical intensive care unit (ICU) patients using clinical, radiographic, and bacteriological parameters in a prospective concurrent fashion. METHODS: This clinical study enrolled all surgical, trauma, and neurosurgical patients admitted to a surgical ICU over a 13-month period. Routine surveillance was used to identify those patients suspected of developing nosocomial pneumonia. Numerous clinical parameters concerning ventilatory support, acute lung injury, organ dysfunction, nutrition, and length of stays were used to identify factors disposing to development of pneumonia. Univariate and multivariate analyses were used for this purpose. Patients thought to have pneumonia were then followed concurrently to determine, as closely as possible, whether pneumonia was present by serial examination of clinical, bacteriologic, and radiographic data. Those "validated" by this process were then compared to those "nonvalidated" to see if any distinction could be made. RESULTS: Of the 352 patients enrolled, 46 (13%) were initially labeled as having developed nosocomial pneumonia when compared to the 306 patients without pneumonia. Univariate analysis demonstrated a greater need for intubation and mechanical ventilation, longer mechanical ventilation, more acute lung injury, longer ICU and hospital stays, poorer nutrition, and higher mortality (17% versus 5%, P < 0.01). Multivariate analysis demonstrated only length of ICU stay and length of intubation/mechanical ventilation as longer in the pneumonia group. On further concurrent review, 23 of 46 patients were validated as having pneumonia while the rest were felt not to have pneumonia. When the two groups were compared, only asymmetric and segmental radiographic infiltrates distinguished validated from nonvalidated pneumonia patients and all other clinical parameters, including mortality and length of stay, were similar. CONCLUSION: Nosocomial pneumonia was initially suspected in 13% of this ICU population. Numerous clinical parameters clearly distinguished these pneumonia patients from others and they suffered a substantially higher mortality. However, within this pneumonia group, only half of the patients could be validated as truly having pneumonia using available clinical parameters. Nevertheless, those validated were indistinguishable in their clinical behavior from those who were not. This calls into question the need for elaborate and sometimes expensive investigations for diagnosis of nosocomial pneumonia.

Adult↗

PubMed1995

Expression of fructosyllysine receptors on human monocytes and monocyte-like cell lines.

Short-term exposure of human serum albumin to glucose in vitro results in the formation of fructosyllysine residues. Using short-term glucose-modified albumin the interactions with human monocytes and with the human monocyte-like cells U937, MonoMac 6, HL60, and THP1 were studied. Short-term glycated albumin was specifically bound by monocytes, U937 and MonoMac 6 cells, but not by HL60 and THP1 cells. This specific binding of short-term glycated albumin was inhibited by fructosyllysine, but not by hexitollysine. Short-term glycated albumin did not compete for binding of albumin, modified by advanced glycation end products. Scatchard analysis of the binding data indicated that there are 10,000 binding sites per cell in monocytes or U937 cells and 2000 sites per cell on MonoMac 6 cells with affinity constants of 9 x 10(6) M-1. Specific binding of short-term glycated albumin to human monocytes was observed in 29% of the 101 human subjects investigated. Ligand-receptor cross-linking and ligand blotting experiments revealed two binding proteins of 100 to 110 and 190 kDa in SDS-PAGE after membrane protein solubilization of U937 and MonoMac 6 cells. The binding of short-term glycated albumin to MonoMac 6 cells induced the production of the cytokines IL-1 and TNF.

Binding Sites↗

PubMed1995

Purification and partial amino acid sequencing of a fructosyllysine-specific binding protein from cell membranes of the monocyte-like cell line U937.

The ability of short-term in vitro glycated albumin to react with monocytes or the monocyte-like cells U937 is due to the Amadori adduct fructosyllysine. Two binding proteins of about 100 and 200 kDa have been previously described to interact specifically with the monocyte-like cell line U937. Detergent extracts from U937 cell membranes were used to purify the 100kDa protein by ion exchange chromatography, fructosyllysine-Sepharose affinity chromatography and SDS-PAGE. Six amino acids from the N-terminal end and two peptide sequences of 14 and 15 amino acids were identical with the N-terminus and the positions 349 to 362 and 610 to 624 of the major nuclear protein nucleolin. However, ligand blotting experiments with nuclear extracts from U937 and RIN cells showed no binding of glycated albumin with nucleolin. The reported amino acid sequences of the 100kDa fructosyllysine specific binding protein do not show any homologies with AGE-receptors. This receptor protein as a nucleolin-like polypeptide belongs to the superfamily of RNA-binding proteins.

Amino Acid Sequence↗

PubMed1995

Characterization of current exposure to man-made vitreous fibres (MMVF) in the prefabricated house industry in Sweden.

The exposure to man-made vitreous fibres (MMVF) was investigated at 11 Swedish plants manufacturing prefabricated wooden houses. Current fibre levels were studied by monitoring personal exposure using the membrane filter technique. All samples were analysed by phase contrast optical microscopy (PCOM) according to Swedish standard rules; they were also analysed using a set of modified criteria for fibre counting, developed for this study, which in addition also required straight, parallel and/or convergent edges of the fibres. The objective of this alternating counting method, the modified fibre method, was to exclude fibres with appearance other than MMVF, that might be present in the wood industries. The method was validated by scanning electron microscopy (SEM). In all, 120 samples were taken and 273 analyses were performed. The mean exposure (GM), analysed by the standard method, was for insulators 0.10 f ml-1 (range 0.03-0.30 f ml-1) and for woodcutters 0.09 f ml-1) (range 0.05-0.19 f ml-1). Analysed by the modified fibre method the insulators were exposed to 0.029 f ml-1 (range 0.013-0.077 f ml-1 and the cutters to 0.021 f ml-1 (range 0.014-0.033 f ml-1). A significant difference was observed between the exposure for near-field workers/job titles and far-field workers/job titles. Analysis of fibre levels by the modified fibre method indicated that only a minor proportion, around 25%, of the total airborne fibres were MMVFs. The reliability of the alternative modified counting method was high, and a high correlation (r = 0.94) with the SEM results was also achieved.

Calcium Compounds↗

PubMed1995

An index of past asbestos exposure as applied to car and bus mechanics.

Different ways to describe historic fibre exposure from asbestos-containing friction materials were studied and compared for a group of 103 car and bus mechanics with more than 20 years employment and 15 years of asbestos exposure. A model was constructed to calculate cumulative asbestos exposure from friction materials including duration, intensity and exposure last year. The model is a combination of an additive and a multiplicative model, where an asbestos index was constructed that takes both near field and far field exposure into consideration. The model was based upon data from the international literature and quantitative asbestos measurements performed 1976-1988 in Swedish car repair workshops. The fibres were counted by phase-contrast microscopy with fibre criteria of length > 5 microns and aspect ratio > or = 3:1. The mechanics' fibre exposure at 398 repair workshops during a period of 48 years were calculated using the model. The mean cumulative exposure was estimated to be 2.6 f ml-1 * year. The annual cumulative exposure was highest for truck mechanics in the early 1960s. The car mechanics had a time-weighted average fibre exposure range of 0.11-0.41 f ml-1 (mean 0.21 f ml-1) in 1965 compared to 0.003-0.08 f ml-1 (mean 0.021 f ml-1) in 1985. In order to validate the model, the mechanic's fibre exposure estimated using the model were compared with representative asbestos exposure measurements for car mechanics during the 1960s and the 1970s (correlation coefficient = 0.69). Five lung physiological variables (FVC, TLC, FEV1, TLco and CV%) were used to study exposure-response relationships. None of the exposure parameters suggested any significant relationship between exposure and decrease in lung function.

Adult↗

PubMed1995

Fiber exposure assessment in the Swedish rock wool and slag wool production industry in 1938-1990.

OBJECTIVE: A multiplicative model was developed to assess past exposure to respirable fibers among rock wool and slag wool production workers in Sweden in 1938-1990. METHODS: Information on the job titles, work tasks and employment times of 1487 workers exposed to man-made vitreous fibers was obtained from company records and interviews with older employees. A mathematical model developed earlier for assessing historical fiber exposure, based on factory averages, was further developed. Matrices of multipliers for each plant that were specific for job title were modified to assess fiber exposure with respect to job title and calendar period. The model was based on measurements made in 1977. Two methods of exposure assessment were compared, cumulative exposure based on factory average (model I) and cumulative exposure based on job title (model II). RESULTS: The exposure changed considerably in the two factories during the period 1938-1990, and it varied also between job titles. The estimated average fiber (f) exposure level at the two plants in the middle of the 1940s was 1.32 and 0.78 f.ml-1. These values are 26 and 16 times higher, respectively, than the exposure in 1980. Process changes, as well as the addition of binders and oil, reduced the exposure drastically around 1950. The mean cumulative respirable fiber exposure for the 1487 subjects was 1.44 (range 0.05-18.40) f.ml-1.year. The cleaners had 14 times higher annual fiber exposure than the preproduction workers. CONCLUSIONS: Model II was judged to be more valid than model I in assessing exposure to man-made vitreous fibers.

Adult↗

PubMed1995

Cancer incidence, mortality and exposure-response among Swedish man-made vitreous fiber production workers.

OBJECTIVE: The objective of this study was to provide an extended follow-up of workers in three Swedish plants producing man-made vitreous fibers (MMVF). METHOD: Mortality and cancer incidence was investigated among 3539 male and female workers, employed for at least one year before 1978. Mortality was followed from 1952 to 1990 and cancer incidence from 1958 to 1989. National and regional mortality and cancer incidence rates were used to calculate the expected numbers. RESULTS: Twenty-seven lung cancer deaths were observed compared with 23 expected (standardized mortality ratio 117, 95% confidence interval 81-176), based on regional mortality. With a latency time of 30 years, the lung cancer risk was significantly elevated, but not trend was found for the standardized mortality ratio with increasing duration of exposure to MMVF. The lung cancer and stomach cancer mortality was higher in the rock wool industry than in the fiber glass industry. Fiber exposure from 1938 to 1990 was estimated in the two rock wool plants by applying a model for historical fiber exposure estimation, specific for different job titles in the rock wool production industry. No relationship was found between individually cumulated rock wool fiber exposure and lung cancer or stomach cancer risk. CONCLUSIONS: The numbers of lung cancers and stomach cancer cases were low and did not therefore allow more general conclusions regarding the cancer hazard for exposed workers. A large European study in progress will probably allow more precise conclusions.

Adult↗