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Biomedical subjects

U Johansson

Publications and source records attributed to U Johansson.

At least 19 recordsLinked to original sources

Key factors for human islet isolation and clinical transplantation.

BACKGROUND: To further improve the outcome of clinical islet transplantation analysis of the impact of donor- and process-related factors could be of great importance. MATERIALS AND METHODS: Thirty-eight consecutive clinical islet transplantations were performed with consecutive islet isolations. Univariate analysis for donor- and isolation-related variables were correlated with recipient C-peptide levels at 2 and 4 weeks after transplantation. "Warm ischemia time" was defined as the time from start of University of Wisconsin solution perfusion in the donor until the pancreas was removed to the back table. RESULTS: Short "warm ischemia time" (WIT), low expression of tissue factor (TF) in pancreatic tissue, and high creatinine levels in the donor were variables related to high C-peptide values after islet transplantation. Furthermore, hospitalization length longer than 4 days was associated with low C-peptide levels. The number of islet equivalents (IEQ) did not correlate with the clinical outcome, possibly due to the fact that IEQ number was included in the release criteria for clinical islet transplantation CONCLUSIONS: Successful clinical islet transplantation is strongly correlated with donor and pancreas procurement factors rather than isolation process-related variables. "WIT" may induce TF expression in the pancreatic tissues. TF has been identified as the main trigger of the instant blood-mediated-inflammatory reaction in clinical islet transplantation. Therefore, assay of TF expression in pancreatic tissues could be applied as useful screening tool to identify "good" pancreata for clinical transplantation.

Analysis of Variance↗

Intakes of plant foods, fibre and fat and risk of breast cancer--a prospective study in the Malmö Diet and Cancer cohort.

The objective of this study was to investigate prospectively the associations between intakes of plant foods, fibre and relative fat and risk of breast cancer in a subsample of 11 726 postmenopausal women in the Malmö Diet and Cancer cohort. Data were obtained by an interview-based diet history method, a structured questionnaire, anthropometrical measurements and national and regional cancer registries. During 89 602 person-years of follow-up, 342 incident cases were documented. Cox regression analysis examined breast cancer risks adjusted for potential confounders. High fibre intakes were associated with a lower risk of postmenopausal breast cancer, incidence rate ratio=0.58, 95% CI: 0.40, 0.84, for the highest quintile of fibre intake compared to the lowest quintile. The combination high fibre-low fat had the lowest risk when examining the effect in each cell of cross-classified tertiles of fibre and fat intakes. An interaction (P=0.049) was found between fibre- and fat-tertiles. There was no significant association between breast cancer risk and intakes of any of the plant food subgroups. These findings support the hypothesis that a dietary pattern characterised by high fibre and low fat intakes is associated with a lower risk of postmenopausal breast cancer.

Aged↗

Ligation of CD47 during monocyte differentiation into dendritic cells results in reduced capacity for interleukin-12 production.

We have previously shown that the CD47-binding thrombospondin-1 (TSP-1)-derived peptide 4N1K induces a rapid apoptosis-like death of human monocytes and dendritic cells (DCs). However, not all cells were susceptible to the peptide-induced cell death and here, we have investigated whether surviving monocytes could differentiate into functionally normal DCs. We found that the cell-surface phenotype, the T-cell stimulatory capacity and the ability to undergo lipopolysaccharide (LPS)-induced maturation into CD83+ DCs were essentially identical in 4N1K-derived and control DCs. Interleukin-10 (IL-10) production was also normal, but a significant downregulation of the pro-inflammatory cytokines IL-12 and tumour necrosis factor-alpha (TNF-alpha) was observed in the 4N1K-derived DCs. To the contrary, simultaneous stimulation of control DCs with 4N1K and LPS + interferon-gamma did not alter IL-12 production. These results indicate that although activation of the TSP-1-binding region of CD47 on monocytes induces apoptosis in a large proportion of the cells, it does not hamper the overall capacity of the surviving cells to differentiate into DCs. Such DCs, however, have a reduced capacity for IL-12 and TNF-alpha production, and the possibility that this is linked to the uptake of apoptotic cells is discussed.

Anabasine↗

CD47 ligation induces a rapid caspase-independent apoptosis-like cell death in human monocytes and dendritic cells.

CD47 is a versatile cell-surface molecule expressed on nearly all haematopoietic cells. In its capacity as a thrombospondin-1 (TSP-1) receptor, CD47 has recently been shown to mediate cell death in certain cells, for example, activated but not resting T cells. Here, we have investigated the possibility that human monocytes and dendritic cells (DCs) undergo cell death, following CD47 ligation. Using the TSP-1-derived CD47-binding peptide 4N1K, we found that both freshly isolated monocytes and monocyte-derived DCs underwent a rapid, caspase-independent cell death. This was characterized by the simultaneous presence of phosphatidylserine exposure, plasma membrane permeability, reduced mitochondrial membrane potential and highly fragmented DNA. Not all cells were sensitive to 4N1K-induced apoptosis; a plateau of cell death reached at an average of 38% of the monocyte and DCs populations. The results presented here, thus, show that CD47 can mediate a rapid apoptosis-like cell death of human monocytes and DCs.

Antigens, CD↗

Two new HLA Cw* alleles, Cw*0105 and Cw*1405, detected by sequence based typing.

During recent years, the view of the relative importance of the HLA Cw locus has undergone substantial change. From being an HLA locus with both limited polymorphism and biological significance there are now more than a hundred different alleles known and the biological importance of HLA Cw, both as a transplantation antigen and as a receptor for NK cells, is well established. Sequence based typing has been shown to be a powerful tool, especially for HLA Cw typing. Here we describe two new HLA Cw* alleles found during routine typing of potential bone marrow donors and hematological patients. The HLA Cw*0105 differs from Cw*0102 at positions 361 and 368 in exon 3 leading to a Trp to Arg and Cys to Ser substitution, respectively. HLA Cw*1405 differs from Cw*14021 by a single nucleotide substitution at position 368. This mutation results in an amino acid substitution of Phe for Tyr.

Alleles↗

Identification of a new HLA-DPB1 allele,HLA-DPB1*9001.

During routine typing of a potential bone marrow donor, a new HLA DPB1 allele was identified. The new allele, officially named HLA DPB1*9001, differs from HLA DPB1*01011 in the second hypervariable region, where a single nucleotide substitution in position 191 changes the codon 35 from TAC to TTC with a predicted amino acid change from Tyr to Phe.

Alleles↗

Identification of a new isoform of human IL-12 p35 mRNA.

This study has identified an alternate mRNA isoform of the human interleukin-12 p35 gene differing from normal p35 transcripts by the deletion of exon 3. Exon 3-lacking p35 mRNA was produced by both dendritic cells and Epstein-Barr virus-transformed B cells and was detected only when transcription of normal p35 mRNA was abundant.

Alternative Splicing↗

Predicting return to work after brain injury using occupational therapy assessments.

PURPOSE: The aim of this study was to evaluate the value of occupational therapy assessments used in an outreach rehabilitation programme to predict return to work after brain injury. The assessments represent the ICIDH-2 levels of body function and activity. METHOD: Fifty-six persons in a late phase after brain injury who had been admitted to the rehabilitation programme during 2 years were followed up according to work status. The follow up was made at a minimum of 2 years after injury. Demographic data and scores from the occupational therapy assessments were compared for the two groups who were back to work or studies (BTW) and not back to work or studies (NBTW). RESULTS: Assessments of memory, visual perception and apraxia separated between the two groups BTW and NBTW. Logistic regression showed that memory score in combination with data on PADL made up the best predictive model. In a subgroup with 21 persons where data on IADL were added to memory and PADL the predictive value was even stronger. CONCLUSIONS: In this study we found that occupational therapy assessments were valuable in predicting failure to return to work or studies after brain injury.

Adolescent↗

Reducing the time of co-incubation of gametes in human in-vitro fertilization has no beneficial effects.

Reports concerning the benefit of reducing the co-incubation time of gametes in connection with IVF have been conflicting. The present randomized study was undertaken to determine whether a reduced co-incubation time would improve the embryo development and consequently the pregnancy and implantation rates. Oocytes from 87 patients were collected and half the oocytes from each patient (n = 488, group A) were randomized to 2 h incubation and the other half (n = 504, group B) to overnight incubation. The oocytes were then cultured according to our standard procedure. Significant difference (P = 0.02) was observed between the two groups regarding fertilization rate and polyspermy (group A 72.5%, 3% and group B 80.5%, 6% respectively). However, no difference was observed in further development and morphology of the embryos. The two embryos with the best morphological score were selected for transfer. No significant difference was found between the different transfer groups regarding positive serum HCG and implantation rate. CONCLUSION: The present results and results from previously published studies indicate that the most important factor in connection with the culture method currently used is the amount of sperm added for co-incubation. This should be optimized to reduce the concentration of harmful sperm waste products and create optimal culture conditions.

Journal Article↗

Does pronuclear morphology and/or early cleavage rate predict embryo implantation potential?

A total of 340 patients referred for in-vitro fertilization was included in a retrospective, comparative study in which zygotes were studied regarding alignment and polarization of nucleolar precursor bodies (NPB) and also early cleavage in relation to implantation and pregnancy rates for the 680 transferred embryos. At assessment of the pronucleus 18-19 h after sperm injection, NPB were checked for alignment/polarization. Twenty-six hours after sperm insemination the zygotes were assessed for early cleavage. At embryo transfer the two embryos with the best morphological score, irrespective of polarization and early cleavage, were selected for transfer. The overall rate of positive HCG tests 17 days after embryo transfer was 42% and the implantation rate 23%. Fourteen percent of the patients received two embryos with polarized NPB, with a positive HCG test of 51%. Embryo transfer with early-cleaved embryos was carried out in 21% of the cycles, with a pregnancy rate of 45%. Embryos with polarized NPB and/or early cleavage were transferred in 34% of the cycles, with a pregnancy rate of 51%, compared with a pregnancy rate of 38% when none of the embryos fulfilled these criteria (P-value 0.02). In this study the pregnancy rate was significantly higher when one or two embryos were polarized and/or early cleaved. It is concluded that in a cohort of morphologically good embryos, assessment for alignment/polarization of NPB and/or early cleavage can, together with conventional morphological criteria, serve as a simple non-invasive method for selection of embryos with high implantation potential.

Journal Article↗

Germline BRCA1 and HMLH1 mutations in a family with male and female breast carcinoma.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disease, predisposing to the development of colorectal cancer and other tumor types such as endometrial, small bowel, stomach, ovary and urinary tract carcinoma, while most investigators find no association between HNPCC and cancer of the breast. We have identified hMLH1 mutations in 2 Amsterdam-criteria HNPCC families where both male and female gene carriers were affected with breast cancer. To investigate whether these breast cancers were caused by other genetic factors, we analyzed the 2 breast cancer susceptibility genes BRCA1 and BRCA2. In one family we did not find any mutation in the breast cancer genes, while in the other, a BRCA1 mutation segregated in the breast cancer cases. Hereditary breast cancer, and in particular BRCA1 tumors, display discrete histo-pathological and immunohistological characteristics. The tumor from a woman with both hMLH1 mutations and a BRCA1 mutation exhibited typical BRCA1 histology, e.g., grade 3 invasive ductal carcinoma with dense lymphocytic infiltration, and immunohistology, estrogen receptor (ER) negative, progesterone receptor (PgR) negative, strongly p53 positive, c-erbB-2 negative and highly Ki67 positive (>50% stained cells). The histology of the breast tumor from the man with both one hMLH1 mutation and a BRCA1 mutation was a grade 2 invasive ductal carcinoma without any special BRCA1 features. Immunohistology was also different. This might merely reflect a true difference in male breast tumor progression vs. female. We cannot exclude that the combined effect of BRCA1 and hMLH1 dysfunction has a bearing on tumor progression.

Adaptor Proteins, Signal Transducing↗

Fruit and vegetable consumption in relation to risk factors for cancer: a report from the Malmö Diet and Cancer Study.

OBJECTIVE: To examine the associations between the consumption of fruit and vegetables and other markers of cancer risk. DESIGN: A cross-sectional survey within the population-based prospective Malmö Diet and Cancer (MDC) Study. Information on food habits was collected through the modified diet history method designed and validated for the MDC Study. Data on smoking and alcohol habits, leisure time physical activity, birth country, education, socioeconomic status and cohabitation status were collected through a questionnaire. SETTING: Malmö, the third largest city in Sweden. SUBJECTS: All subjects who entered the MDC Study during winter 1991 to summer 1994 (men and women living in Malmö, aged between 46 and 68 years), with a total of 15 173. RESULTS: Women consumed more fruit and vegetables than men. Low consumption of both fruits and vegetables was associated with unfavourable nutrient profiles: higher percentage of energy from fat and lower intakes of antioxidant nutrients and dietary fibre. Low consumption was also associated with smoking, low leisure time physical activity, low education and being born in Sweden. High age was associated with low vegetable consumption in both genders. CONCLUSION: This study indicates that several established risk markers and risk factors of cancer may be independently associated with low fruit and vegetable consumption. The findings suggest that the adverse effects of factors such as smoking, low physical activity and a high-fat diet could partly be explained by low consumption of fruit or vegetables. The implied health benefits of a low or moderate alcohol consumption may be similarly confounded by high consumption of fruit or vegetables.

Aged↗

Enriched environment increases neurogenesis in the adult rat dentate gyrus and improves spatial memory.

The fetal and even the young brain possesses a considerable degree of plasticity. The plasticity and rate of neurogenesis in the adult brain is much less pronounced. The present study was conducted to investigate whether housing conditions affect neurogenesis, learning, and memory in adult rats. Three-month-old rats housed either in isolation or in an enriched environment were injected intraperitoneally with bromodeoxyuridine (BrdU) to detect proliferation among progenitor cells and to follow their fate in the dentate gyrus. The rats were sacrificed either 1 day or 4 weeks after BrdU injections. This experimental paradigm allows for discrimination between proliferative effects and survival effects on the newborn progenitors elicited by different housing conditions. The number of newborn cells in the dentate gyrus was not altered 1 day after BrdU injections. In contrast, the number of surviving progenitors 1 month after BrdU injections was markedly increased in animals housed in an enriched environment. The relative ratio of neurogenesis and gliogenesis was not affected by environmental conditions, as estimated by double-labeling immunofluorescence staining with antibodies against BrdU and either the neuronal marker calbindin D28k or the glial marker GFAp, resulting in a net increase in neurogenesis in animals housed in an enriched environment. Furthermore, we show that adult rats housed in an enriched environment show improved performance in a spatial learning test. The results suggest that environmental cues can enhance neurogenesis in the adult hippocampal region, which is associated with improved spatial memory.

Aging↗

Dietary patterns in high and low consumers of meat in a Swedish cohort study.

The objective was to examine relationships between meat and other food items which have been associated with higher risk of cancer in the colon and prostate in some epidemiological studies. The study was conducted as a population-based cohort study comprising 11648 subjects (4816 male and 6742 female) born between 1926 and 1945 and living in the city of Malmö, Sweden. Data on mean daily intake of foods and nutrients were assessed with a diet history method combining a 7-day menu book and a food frequency questionnaire. Increasing meat intake, expressed in quintiles and adjusted for energy, was associated with decreasing intakes of poultry, fish, fruits, bread, cereals and cheese in both sexes. Low negative correlations between meat intake and ascorbic acid (r= -0.11) and fiber (r= -0.16 to -0.20) were noted. The average intake of fat from meat out of total fat intake was 13.6% in men and 11.9% in women. No major associations were noted between meat and the cholesterol raising fatty acids C:12:0, C:14:0, C:160 nor for C:20:4 or its precursor C:18:2. In conclusion, our findings indicate that meat consumption is negatively associated with food groups rich in antioxidants and fiber and the positive covariance reported between meat and cancer and coronary heart disease might, therefore, not be directly linked to components in meat.

Adult↗