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Biomedical subjects

S Johansson

Publications and source records attributed to S Johansson.

At least 73 records · Page 4Linked to original sources

Calcaneal ultrasound measurements are determined by age and physical activity. Studies in two Swedish random population samples.

AIM: To present reference values and correlations with body composition, blood variables and lifestyle factors. SUBJECTS: Two random population samples from Göteborg, Sweden, one comprising 184 men and 455 women aged 25-64 years (MONICA) and the other 860 women aged 55-82 years (BEDA) were studied. METHODS: Calcaneal ultrasound measurement (LUNAR Achilles) and bioimpedance were measured. Smoking habits, coffee consumption, physical activity, psychological stress, education and marital status, as well as blood lipids, blood pressure, and fractures were studied. RESULTS: Broadband ultrasound attenuation and stiffness were higher in men than in women (P < 0. 001), but speed of sound did not differ between sexes. Speed of sound, broadband ultrasound attenuation and stiffness decreased with age (P < 0.001). In both sexes speed of sound, broadband ultrasound attenuation and stiffness correlated positively to body size variables, and negatively with smoking in women after adjustment for age. Speed of sound, broadband ultrasound attenuation and stiffness were positively related to physical activity in both sexes, and these relationships were the only ones that remained in multivariate analyses in addition to age (negative). Osteoporotic fractures increased with age. Speed of sound, broadband ultrasound attenuation and stiffness were lower amongst women with osteoporotic fractures. CONCLUSION: Speed of sound, broadband ultrasound attenuation and stiffness decreased with age and increased with physical activity, but body weight and height were not correlated in multivariate analyses. Osteoporotic fractures increased with age and were associated with lower calcaneal ultrasound values.

Adult↗

Ipsilateral local recurrence in relation to therapy and morphological characteristics in patients with ductal carcinoma in situ of the breast.

METHOD AND RESULTS: A standardized histopathological protocol has been designed, in which different histological characteristics of ductal carcinoma in situ (DCIS) are reported: nuclear grade (ng), growth pattern according to Andersen et al., necrosis, size of the lesion, resection margins and focality. Using this protocol a re-evaluation of a population-based consecutive series of 306 cases of DCIS has been done as well as a thorough clinical follow-up. After a median follow-up of 63 months, 13% have developed ipsilateral local recurrences, invasive and/or in situ. Ipsilateral local recurrence-free survival (IL-RFS) was significantly better for patients operated with mastectomy (ME) or breast conserving therapy (BCT) with radiotherapy (RT) than for patients operated with BCT without RT (5-year IL-RFS 96% vs 94% vs 79%, P<0.001). In the subgroup of BCT without RT there were significant differences in IL-RFS between histopathological subgroups: ng 1 + 2 (non-high grade) vs ng 3 (high grade; P=0.014), non-high-grade without comedo-type necrosis vs non-high-grade with comedo-type necrosis vs high-grade (the Van Nuys classification system; P=0.025). Growth pattern (not diffuse vs diffuse) and margins (free vs involved or not evaluated) showed a tendency (P=0.07 and 0.05, respectively) to be associated to IL-RFS. In contrast, no significant differences in IL-RFS were found in subgroups based on mode of detection, focality or size. Ninety-four per cent of the local recurrences after BCT appeared at the previous operation site. CONCLUSIONS: In the BCT without RT group, combinations of either non-high grade and not a diffuse growth pattern or non-high grade and free margins identified groups (constituting approximately 30% of the patients) were at low risk of developing ipsilateral recurrences (6-10%), compared to a 31-37% recurrence risk in the remaining groups during the observed follow-up time. The beneficial effect of post-operative RT for these low-risk groups can be questioned, and should be studied further.

Adult↗

Cellular invasion by Staphylococcus aureus involves a fibronectin bridge between the bacterial fibronectin-binding MSCRAMMs and host cell beta1 integrins.

Although Staphylococcus aureus is primarily considered an extracellular pathogen, recent evidence suggests that this bacterium can invade a variety of nonprofessional phagocytic cells. Here we investigate the early stages of cellular invasion by S. aureus and determine the bacterial and host components that are required for this process. S. aureus expresses two cell surface-associated fibronectin (FN)-binding proteins (FnbpA and FnbpB) that mediate the interaction of the bacteria with both soluble and solid-phase FN in vitro. Using a mutant of S. aureus that lacks the expression of both Fnbps, we show that the expression of either protein is necessary for efficient uptake by the mouse fibroblast line GD25beta1A. Invasion could be inhibited by soluble recombinant proteins encompassing either the FN-binding D repeat region or the A region (and B repeats) of FnbpA, suggesting that the activities of both regions are important in this process. We demonstrate that FN is also required for invasion of this cell line. In the presence of FN-depleted fetal bovine serum, the invasion level was reduced by approximately 40% compared to in the presence of whole fetal bovine serum. Invasion could be further reduced by the addition of anti-mouse FN antibodies to the assay. Finally, we utilize a mutant mouse fibroblast line, which lacks beta1 integrin expression, to demonstrate that host cell beta1 integrins are necessary for efficient cellular invasion. The level of invasion of the mutant cell line GD25 was reduced by approximately 97% compared to the beta1-expressing complemented cell line GD25beta1A. In addition, invasion of the GD25beta1A cell line could be inhibited by an RGD-containing peptide, further implicating a role for integrins in this process. Based on these observations, we put forward a model of S. aureus invasion in which host FN forms a bridge between the bacterial Fnbps and host cell beta1 integrins, leading to bacterial uptake.

Adhesins, Bacterial↗

Detection of colorectal tumor and inflammatory bowel disease during follow-up of patients with initial diagnosis of irritable bowel syndrome.

BACKGROUND: We wanted to estimate the incidence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) in the general population, and the detection of colorectal tumor (CRT) and inflammatory bowel disease (IBD) after the diagnosis of IBS and FD. METHODS: Patients aged 20-79 years newly diagnosed with IBS (N = 2956) or FD (N = 9900), together with a comparison cohort randomly sampled from the general source population, were followed-up during a mean time of 3 years. RESULTS: We found an overall incidence of 10.3 per 1000 person-years for FD and 2.6 per 1000 person-years for IBS. There was a greater prevalence of depression, stress, fatigue, and pain disorders among IBS and FD patients than in the general population. During the 1st year after a diagnosis of IBS the cumulative risk of detecting CRT was close to 1% in IBS patients. After the 1st year the risk of CRT in IBS patients was close to that in the general population. We found a significantly increased risk of detecting IBD among patients initially diagnosed as having IBS (relative risk (RR), 16.3; 95% confidence interval (CI), 6.6-40.7), which was constant during all the follow-up period. No association was found between dyspepsia and CRT, or IBD. CONCLUSION: IBS and FD shared some comorbidity features, yet demographics and incidence rates were different. Unlike the detection of colorectal tumor, the excess risk of IBD after an initial diagnosis of IBS was cumulatively increased during all the follow-up period. The continuously increased risk of IBD detection in IBS patients favors a true association between IBS and IBD.

Adult↗

Histologic grading in breast cancer--reproducibility between seven pathologic departments. South Sweden Breast Cancer Group.

Histologic grade, including tubular formations, nuclear grade, and mitotic activity, is a well-documented prognostic factor in breast cancer. In comparison with other prognostic parameters, the evaluation of histologic grade is cheap and can be performed, in principle, in all cases of breast cancer. One possible disadvantage is that the evaluation may vary between different pathological departments. The aim of the present work was therefore to study the reproducibility of the histologic grading system by distributing haematoxylin-erythrosin-stained slides from 93 invasive breast cancers to the seven pathology departments within the southern healthcare region of Sweden. The evaluation was performed blindly and without any knowledge of other clinical parameters. In 31% of the cases the same histologic grade was obtained for all departments. The overall mean kappa was 0.54, indicating a moderate reproducibility. Of the three factors included in histologic grade, the agreement was best for tubular formations and poorest for nuclear grade and mitotic activity. The overall moderate reproducibility should be considered when the clinical usefulness of histologic grading is compared with other prognostic instruments.

Adult↗

Brachial plexopathy after postoperative radiotherapy of breast cancer patients--a long-term follow-up.

In 1963-1965 a group of 71 patients operated on for breast cancer with total mastectomy and axillary clearance were given aggressive postoperative telecobalt therapy to the axillary, supraclavicular and parasternal lymph node regions. The prescribed dose to these lymph node regions was 44 Gy in 11 fractions. Only two of the three fields were treated per day. Retrospective dose calculations showed that the total dose in the brachial plexus from the axillary and supraclavicular fields was c. 57 Gy in 16-17 fractions over 3-4 weeks. After a few years, symptoms and signs of brachial plexus injury appeared in many patients, which was reported in some early papers. The cohort has now been followed-up to 34 years. As expected, there was progression of both prevalence and severity of the late effects between 5 and 34 years and 11 of 12 patients who are still alive have paralysis of their arms. The neuropathy seems to be closely linked to fibrosis around the nerve trunks. The use of large daily fractions, in some cases combined with hot spots from overlapping fields, was certainly the cause of the complication.

Adult↗

The cytoplasmic tyrosines of integrin subunit beta1 are involved in focal adhesion kinase activation.

We have previously shown that mutation of the two tyrosines in the cytoplasmic domain of integrin subunit beta1 (Y783 and Y795) to phenylalanines markedly reduces the capability of beta1A integrins to mediate directed cell migration. In this study, beta1-dependent cell spreading was found to be delayed in GD25 cells expressing beta1A(Y783/795F) compared to that in wild-type GD25-beta1A. Focal adhesion kinase (FAK) tyrosine phosphorylation and activation were severely impaired in response to beta1-dependent adhesion in GD25-beta1A(Y783/795F) cells compared to that in wild-type GD25-beta1A or mutants in which only a single tyrosine was altered (beta1A(Y783F) or beta1A(Y795F)). Phosphorylation site-specific antibodies selective for FAK phosphotyrosine 397 indicated that the defect in FAK phosphorylation via beta1A(Y783/795F) lies at the level of the initial autophosphorylation step. Indeed, beta1A-dependent tyrosine phosphorylation of tensin and paxillin was lost in the beta1A(Y783/795F) cells, consistent with the impairment in FAK activation. In contrast, p130(CAS) overall tyrosine phosphorylation was unaffected by the beta1 mutations. Despite the defect in beta1-mediated FAK activation, FAK was still localized to focal adhesions. Taken together, the phenotype of the GD25-beta1A(Y783/795F) cells resembles, but is distinct from, the phenotype observed in FAK-null cells. These observations argue that tyrosines 783 and 795 within the cytoplasmic tail of integrin subunit beta1A are critical mediators of FAK activation and cell spreading in GD25 cells.

Amino Acid Substitution↗

Overall mortality among patients surviving an episode of peptic ulcer bleeding.

STUDY OBJECTIVE: The authors investigated whether patients who have survived an acute episode of peptic ulcer bleeding (PUB) have an excess long term all cause mortality compared with the general population free of PUB. DESIGN: Follow up study of previously identified cohort of patients with a PUB episode and a general population cohort. SETTING: The source population included all people aged 30 to 89 years, registered with general practitioners in the United Kingdom. PATIENTS: All patients alive one month after the PUB episode constituted the cohort of PUB patients (n = 978). A control group of 5000 people was randomly sampled from the source population. The same eligibility criteria as for patients with PUB were applied to the control series. Also, controls had to be free of PUB before start date. MAIN RESULTS: Relative risk of mortality among PUB patients was 2.1, 95% CI: 1.7, 2.6) compared with the general population. This increased mortality risk occurred mainly in the patients less than 60 years old. No difference was observed between men and women. The excess mortality was not only circumscribed to deaths attributable to recurrent gastrointestinal bleed, but also cardiovascular, cancer and other causes. CONCLUSIONS: People who have survived an acute episode of PUB have a reduced long term survival compared with the general population. This reduction was stronger among middle age patients than in the elderly.

Adult↗

Determination of the border between the transmembrane and cytoplasmic domains of human integrin subunits.

In this study we have determined the position of the C-terminal end of the transmembrane domains of human integrin subunits (alpha2, alpha5, beta1, beta2) in microsomal membranes using the glycosylation mapping technique. In contrast to the common view, the transmembrane helices were found to extend roughly to Phe(1129) in alpha2, to Phe(1026) in alpha5, to Ile(757) in beta1, and to His(728) in beta2. The alpha-carbon of the conserved lysine present near the C-terminal end of the transmembrane helix (Lys(1125) in alpha2, Lys(1022) in alpha5, Lys(752) in beta1, and Lys(724) in beta2) is buried in the plasma membrane, and the charged amino group most likely reaches into the polar head-group region of the lipid bilayer. A possible role for the conserved lysine in integrin function is discussed.

Amino Acid Motifs↗

Use of cimetidine, omeprazole, and ranitidine in pregnant women and pregnancy outcomes.

Evidence documenting the safety of acid-suppressing drugs in pregnancy is very limited. The authors assessed the prevalence of congenital malformations in first trimester-exposed pregnancies to cimetidine, omeprazole, and ranitidine and compared it with nonexposed pregnancies between 1991 and 1996. Two different sources were used, the United Kingdom General Practice Research Database and the Italian Friuli-Venezia Giulia Health Database. The final study cohort included 1,179 pregnancies from the United Kingdom and 1,057 from Italy. Abortions or ectopic pregnancies were not included. There were 20 stillbirths and 2,261 live-born babies in both cohorts combined, with 100 offspring identified with a malformation. The overall malformation rate was 4.4%. The relative risks for nongenetic congenital malformations associated with the use of cimetidine, omeprazole, and ranitidine were 1.2 (95% confidence interval (CI): 0.6, 2.3), 0.9 (95% CI: 0.3, 2.2), and 1.4 (95% CI: 0.8, 2.4), respectively, compared with the nonexposed. No specific grouping in the distribution of malformations was observed in any of the three exposed groups. Moreover, no relation was found between drug exposure and preterm delivery or growth retardation. These findings suggest that the use of acid-suppressing drugs during the first trimester of pregnancy is not associated with a major teratogenic risk.

Abnormalities, Drug-Induced↗

Beta1 integrin promotes but is not essential for metastasis of ras-myc transformed fibroblasts.

To investigate the role of beta1 integrin during tumor metastasis, we established a ras-myc transformed fibroblastoid cell line with a disrupted beta1 integrin gene on both alleles (GERM 11). Stable transfection of this cell line with an expression vector encoding beta1A integrin resulted in beta1A integrin-expressing sublines. Tumors were induced by subcutaneous injection of GERM 11 cells and 3 independent beta1 integrin expressing sublines (GERM 116, 1A10, 2F2) into syngeneic mice. After 10 days tumors were surgically removed. While average weights of GERM 11 and GERM 116 tumors were similar, tumors induced by the high expressing clones 1A10 and 2F2 were markedly smaller, suggesting an inverse correlation of tumor growth and beta1 integrin expression. The metastasis potential of all three beta1 integrin-expressing GERM 11 sublines tested was significantly higher than that of the beta1-deficient GERM 11 cells. GERM 116 tumors led in all animals to severe metastasis in lung and liver, while GERM 11 tumors induced only a few metastatic foci in the lung. Stroma of both tumors contained nidogen and high amounts of tenascin C, but only a few very low levels of fibronectin, laminin-1, and collagen type I. Beta1 integrin, therefore, increases but is not essential for metastasis of ras-myc transformed fibroblasts.

Alleles↗

Health resource utilization and drug treatment pattern in a cohort of patients with a first episode of gastroesophageal reflux disease.

PURPOSE: To describe the demographics, comorbidity, and health care resource utilization, as well as treatment patterns among gastroesophageal reflux disease (GORD) patients. METHODS: We identified a population-based cohort of newly diagnosed GORD patients receiving cimetidine, ranitidine or omeprazole. Our final study population consisted of 1193 patients, who were followed up for 1 year. RESULTS: Mild symptoms were reported in 44% of cases, moderate in 52%, and 4% had a severe episode. Moderate and severe cases were more likely to undergo endoscopy and to be hospitalized for GORD than mild cases. They also had a higher probability of receiving long-term continuous treatment and to start initial treatment with omeprazole rather than with cimetidine or ranitidine. Initial treatment failure was greater among severe cases and in patients started on H(2)-blockers. CONCLUSION: This study has shown that severity of initial GORD episode is significantly associated with an increased use of health resources, and is the major determinant of initial treatment failure. Patients started on H(2)-blockers also had a greater risk of initial treatment failure compared to patients started on omeprazole.

Journal Article↗

Characterization of a hyaluronan receptor on rat sinusoidal liver endothelial cells and its functional relationship to scavenger receptors.

Hyaluronan is a widely distributed extracellular component of connective tissue with several mechanical and cell biological functions. The serum level of hyaluronan is elevated in rheumatic and liver diseases and in certain malignancies. The major route of hyaluronan clearance from the blood is via the liver, taken up predominantly by sinusoidal liver endothelial cells. We have purified a novel hyaluronan binding protein from liver that also has an affinity for the N-terminal propeptide of type I procollagen, a physiological scavenger receptor ligand. A polyclonal antibody raised against the protein was found to inhibit the binding and degradation of hyaluronan as well as two scavenger receptor ligands by cultured sinusoidal liver endothelial cells. Immunostaining of nonpermeabilized liver cells and liver sections showed that the antibody specifically stains the surface of sinusoidal liver endothelial cells. After pretreatment with monensin to block the recirculation of endocytic receptors, the immunostaining was specifically associated with early endosomes of these cells. Thus, this rat sinusoidal liver endothelial cell hyaluronan receptor shares functional properties with the scavenger receptor family, a group of proteins shown to play a key role in the uptake of atherogenic lipids and other waste products from the tissues.

Animals↗

Signal transduction-mediated adherence and entry of Helicobacter pylori into cultured cells.

BACKGROUND & AIMS: An ability to invade host cells could be a means for Helicobacter pylori to achieve resistance to antibiotic therapy. The aim of this study was to investigate the mechanisms involved in adherence and entry of H. pylori into cultured cells. METHODS: Coinfection with Yersinia expressing mutant or wild-type YopH tyrosine phosphatase was used. Genistein and cytochalasin D were used as inhibitors of adherence and entry; entry was monitored by a gentamicin-protection assay. Target cells were AGS cells and a beta1-integrin-deficient cell line with its corresponding beta1-integrin-expressing transfectant. RESULTS: H. pylori induced phosphorylation of 125-130-kilodalton proteins, similar in size to the target proteins of Yersinia YopH. Adherence of H. pylori was inhibited by Yersinia organisms expressing enzymatically active YopH but not by inactive YopH. Adherence and entry of H. pylori was considerably higher with beta1-integrin-transfected cells than with beta1-integrin-deficient cells. Antibodies directed against alpha5- and beta1-integrin chains reduced adherence to the alpha5beta1-integrin-expressing gastric cell line AGS. Entry was inhibited by both cytochalasin D and genistein. Entry, but not adherence, was higher for 2 type I strains than for a type II isolate. CONCLUSIONS: Invasion of gastric epithelium via an integrin-mediated pathway could contribute to the ability of H. pylori to establish persistent infection.

Bacterial Adhesion↗

The CrescoTi Precision method: description of a simplified method to fabricate titanium superstructures with passive fit to osseointegrated implants.

Casting distortion and inadequate handling in the dental laboratory are 2 factors that can cause misfit between a cast framework and the implant analogs in the master cast. This article describes the CrescoTi Precision procedure, which has been developed for correction of misfit between cast titanium frameworks and supporting dental implants. The simplicity and accuracy of the procedure appear to demonstrate technical progress toward obtaining optimal precision of fit of the superstructure components, thereby eliminating stress forces that may be transformed to the peri-implant bone.

Dental Alloys↗

Echovirus 5: infectious transcripts and complete nucleotide sequence from uncloned cDNA.

Echovirus 5 (EV5) may be isolated from various neurological and exanthematic diseases. To determine the relationship of EV5 to other enteroviruses and for studies of its interactions with the target cell, the complete nucleotide sequence of EV5 was determined. Three overlapping fragments, collectively representing the complete genome, were amplified with RT-PCR and sequenced. Analysis of the EV5 sequence revealed a typical enterovirus-like organization of the genome. To verify that the cDNA generated sequence was derived from infectious viruses, complete EV5 genomes were amplified in one amplicon by long distance PCR. Transfection of in vitro transcribed RNA from these amplicons into cell cultures resulted in replicating EV5. Comparison of the overall nucleotide and amino acid sequences demonstrates that EV5 can be regarded as a coxsackievirus B-like enterovirus. Variable sequences between EV5 and the well characterized coxsackievirus B3 (CVB3) are for the most part observed for amino acid residues that correspond to exposed sequences in the CVB3 capsid. This observation indicates that the reported EV5 strain recently diverged from group B coxsackieviruses.

Amino Acid Sequence↗

Seven novel macrocyclic polypeptides from Viola arvensis.

Seven novel macrocyclic polypeptides, designated as varv peptides B-H, have been isolated from the aerial parts of Viola arvensis. Their primary structures have been elucidated by automated Edman degradation and mass spectrometry. They all consist of 29 or 30 amino acid residues, covalently cyclized via the amide backbone and by three internal disulfide bridges. Their amino acid sequences are as follows: varv peptide B, cyclo-(TCFGGTCNTPGCSCDPWPMCSRNGLPVCGE); varv peptide C, cyclo-(TCVGGTCNTPGCSCSWPVCTRNGVPICGE); varv peptide D, cyclo-(TCVGGSCNTPGCSCSWPVCTRNGLPICGE); varv peptide E, cyclo-(TCVGGTCNTPGCSCSWPVCTRNGLPICGE); varv peptide F, cyclo-(TCTLGTCYTAGCSCSWPVCTRNGVPICGE); varv peptide G, cyclo-(TCFGGTCNTPGCSCDPWPVCSRNGVPVCGE); and varv peptide H, cyclo-(TCFGGTCNTPGCSCETWPVCSRNGLPVCGE). The varv peptides B-H exhibited high degrees of homology with the hitherto known macrocyclic peptides varv peptide A, kalata B1, violapeptide I, circulins A and B, and cyclopsychotride A.

Amino Acid Sequence↗