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Biomedical subjects

C Johansson

Publications and source records attributed to C Johansson.

At least 55 records · Page 3Linked to original sources

Long-term results and functional outcome after Ripstein rectopexy.

PURPOSE: The aim of this study was to evaluate operative mortality, morbidity, and functional results after Ripstein rectopexy for rectal prolapse and internal rectal intussusception. METHODS: Sixty-nine patients with rectal prolapse and 43 with internal rectal intussusception were included. All patient records were studied and complications registered. Long-term follow-up was possible in 105 patients and performed by clinical examination and standardized interview, telephone interview, or patient records. Seventy-six patients were prospectively evaluated, comparing bowel function before and after rectopexy. RESULTS: There was no operative mortality. Operative morbidity was 33 percent, and most complications were minor. Severe early complications included one large-bowel obstruction and one transient ureteric stenosis. Median time of follow-up was seven years in patients with rectal prolapse and 5.4 years in patients with internal rectal intussusception. Late complications included two rectovaginal fistulas and one lethal sigmoid fecaloma. Five patients underwent subtotal colectomy for severe constipation. There was one recurrent prolapse (1.6 percent). Functional evaluation showed that incontinence improved (P = 0.049), whereas the number of bowel movements per week decreased (P < 0.001). Frequency of emptying difficulties did not change significantly in patients with rectal prolapse but increased in patients with internal rectal intussusception (P = 0.038). CONCLUSION: Ripstein rectopexy can be performed with low mortality and recurrence rate, but with a high early complication rate. There were also some serious late complications. Continence was improved, although increased constipation was a problem in some patients, especially among those with internal rectal intussusception.

Adolescent↗

Improved extraction torque of hydroxyapatite-coated pedicle screws.

Loosening of the screws is a problem in instrumentation with pedicle screws. Coating with hydroxyapatite improves the holding characteristics for metal implants, but the possible effects on the anchorage of pedicle screws have not been described. In this study, seven patients were operated on with spinal instrumentation using four stainless steel pedicle screws. Hydroxyapatite-coated screws were used in either the upper or the lower of the instrumented levels. The insertion torque was measured. In four cases the screws were removed after 10-22 months and the extraction torque was measured. The mean insertion torque was found to be significantly greater in the hydroxyapatite-coated screws (107 Ncm) than in the standard screws (76 Ncm). In three cases, the extraction torque for the hydroxyapatite-coated screws exceeded the range for the torque wrench (600 Ncm), while the conventional screws were loose (< 5 Ncm). In one case, the extraction torque was 475 and 550 Ncm for the coated screws, and 5 and 25 Ncm for the conventional screws. The difference in extraction torque was significant. Hydroxyapatite coating was shown to have improved the purchase of pedicle screws very effectively. By using fully coated screws, as in the present study, extraction was extremely difficult compared to extraction of conventional stainless steel screws, which were regularly loose. By reducing the area of the screws that is coated, it may be possible to achieve an enhanced purchase while extraction will be easier when compared to fully coated screws.

Adolescent↗

Association analysis with microsatellite and SNP markers does not support the involvement of BCL-2 in systemic lupus erythematosus in Mexican and Swedish patients and their families.

We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2.

Alleles↗

Positive atopy patch test reactions to Pityrosporum orbiculare in atopic dermatitis patients.

BACKGROUND: Pityrosporum orbiculare, although a part of our normal cutaneous microflora, can cause skin infections and induce specific immunoglobulin (Ig) E antibodies in atopic dermatitis patients. P. orbiculare is therefore considered to be one of the trigger factors for atopic dermatitis. OBJECTIVE: To investigate if P. orbiculare can induce an eczematous reaction in atopic dermatitis patients, seborrhoeic dermatitis patients and healthy controls. METHODS: Fifteen atopic dermatitis patients, eight seborrhoeic dermatitis patients and eight healthy controls were patch tested with extract of P. orbiculare on non-lesional, tape-stripped skin of the back. NaCl was used as a negative control. The patch tests were evaluated after 24, 48 and 72 h. Skin biopsies were taken from P. orbiculare patch test sites at 24 h and 72 h, from NaCl patch test sites at 72 h, from non-lesional skin and, in the atopic dermatitis patients, also from lesional skin. The skin biopsies were investigated with immunohistochemical techniques. P. orbiculare-specific IgE in serum was analysed with RAST. RESULTS: Specific IgE to P. orbiculare was found in serum from 13/15 atopic dermatitis patients and in eight of them a positive patch test reaction to P. orbiculare was observed, with a maximal reaction at 48 h. Significantly higher serum levels of P. orbiculare-specific IgE were detected in patch test-positive compared with patch test-negative atopic dermatitis patients (P < 0. 01). The seborrhoeic dermatitis patients and healthy controls were RAST and patch test-negative for P. orbiculare. In the patch test-positive atopic dermatitis patients an infiltration of CD4+ T cells and eosinophils was observed at the P. orbiculare patch test sites together with an upregulation of ICAM-1 and HLA-DR expression. CONCLUSIONS: P. orbiculare can induce an eczematous reaction in sensitized atopic dermatitis patients and may be an important trigger factor in these patients. The P. orbiculare patch test can be of diagnostic value in this subgroup of atopic dermatitis patients.

Adolescent↗

Histologic evaluation of retrieved craniofacial implants.

A retrieval study was performed on implants placed extraorally in the craniofacial region. The study included 19 implants retrieved from 16 patients. The implants were all stable at the time of removal. For various reasons, 5 of the implants were never loaded, whereas 14 of the implants had a known loading period of 3 months to 7 years 7 months. The reasons for removal varied but included the following: death in 1 case; poor results of the bone-anchored hearing aid in 7 cases; host-related reasons, varying from soft tissue irritation to infection or pain, in 6 cases; change of treatment plan in 1 case; and scheduled direct removal at the time of insertion in 1 case. The results of the histologic evaluation were similar to those reported in retrieval studies of a corresponding design used intraorally.

Adolescent↗

Salmonella infection of bone marrow-derived macrophages and dendritic cells: influence on antigen presentation and initiating an immune response.

Traditionally macrophages (MPhi) have been considered to be the key type of antigen presenting cells (APC) to combat bacterial infections by phagocytosing and destroying bacteria and presenting bacteria-derived antigens to T cells. However, data in recent years have demonstrated that dendritic cells (DC), at their immature stage of differentiation, are capable of phagocytosing particulate antigens including bacteria. Thus, DC may also be important APC for initiating an immune response to bacterial infections. Our studies focus on studying how DC and MPhi process antigens derived from bacteria with no known mechanism of phagosomal escape (i.e. Salmonella typhimurium) for T cell stimulation as well as what role these APC types have in Salmonella infection in vivo. Using an in vitro antigen processing and presentation assay with bone marrow-derived (BM) APC showed that, in addition to peritoneal elicited MPhi and BMMPhi, BMDC can phagocytose and process Escherichia coli and S. typhimurium for peptide presentation on major histocompatibility complex (MHC) class I (MHC-I) and class II MHC-II. These studies showed that both elicited peritoneal MPhi and BMMPhi use an alternate MHC-I presentation pathway that does not require the transporter associated with antigen processing (TAP) or the proteasome and involves peptide loading onto a preformed pool of post-Golgi MHC-I molecules. In contrast, DC process E. coli and S. typhimurium for peptide presentation on MHC-I using the cytosolic MHC-I presentation pathway that requires TAP, the proteasome and uses newly synthesized MHC-I molecules. We further investigated the interaction of Salmonella with BMDC and BMMPhi by analyzing surface molecule expression and cytokine secretion following S. typhimurium infection of BMDC and BMMPhi. These data reveal that Salmonella co-incubation with BMDC as well as BMMPhi results in upregulation of MHC-I and MHC-II as well as several co-stimulatory molecules including CD80 and CD86. Salmonella infection of BMDC or BMMPhi also results in secretion of cytokines including IL-6 and IL-12. Finally, injecting mice with BMDC that have been loaded in vitro with S. typhimurium primes naïve CD4(+) and CD8(+) T cells to Salmonella-encoded antigens. Taken together, our data suggest that DC may be an important type of APC that contributes to the immune response to Salmonella.

Animals↗

Salmonella enterica serovar typhimurium-induced maturation of bone marrow-derived dendritic cells.

Murine bone marrow-derived dendritic cells (DC) can phagocytose and process Salmonella enterica serovar Typhimurium for peptide presentation on major histocompatibility complex class I (MHC-I) and MHC-II molecules. To investigate if a serovar Typhimurium encounter with DC induces maturation and downregulates their ability to present antigens from subsequently encountered bacteria, DC were pulsed with serovar Typhimurium 24 h prior to coincubating with Escherichia coli expressing the model antigen Crl-OVA. Quantitating presentation of OVA epitopes contained within Crl-OVA showed that Salmonella-pulsed DC had a reduced capacity to process Crl-OVA-expressing E. coli for OVA(257-264)/K(b) and OVA(265-277)/I-A(b) presentation. In addition, time course studies of DC pulsed with Crl-OVA-expressing serovar Typhimurium showed that OVA(257-264)/K(b) complexes could stimulate CD8OVA T-hybridoma cells for <24 h following a bacterial pulse, while OVA(265-277)/I-A(b) complexes could stimulate OT4H T-hybridoma cells for >24 but <48 h. The phoP-phoQ virulence locus of serovar Typhimurium also influenced the ability of DC to process Crl-OVA-expressing serovar Typhimurium for OVA(265-277)/I-A(b) presentation but not for OVA(257-264)/K(b) presentation. Furthermore, pulsing of DC with serovar Typhimurium followed by incubation for 24 or 48 h altered surface expression of MHC-I, MHC-II, CD40, CD54, CD80, and CD86, generating a DC population with a uniform, high expression level of these molecules. Finally, neither the serovar Typhimurium phoP-phoQ locus nor lipopolysaccharides (LPS) containing lipid A modifications purified from phoP mutant strains had a different effect on DC maturation from that of wild-type serovar Typhimurium or purified wild-type LPS. Thus, these data show that Salmonella or Salmonella LPS induces maturation of DC and that this process is not altered by the Salmonella phoP virulence locus. However, phoP did influence OVA(265-277)/I-A(b) presentation by DC infected with Crl-OVA-expressing serovar Typhimurium when quantitated after 2 h of bacterial infection.

Animals↗

Isometric force and endurance in soleus muscle of thyroid hormone receptor-alpha(1)- or -beta-deficient mice.

The specific role of each subtype of thyroid hormone receptor (TR) on skeletal muscle function is unclear. We have therefore studied kinetics of isometric twitches and tetani as well as fatigue resistance in isolated soleus muscles of R-alpha(1)- or -beta-deficient mice. The results show 20-40% longer contraction and relaxation times of twitches and tetani in soleus muscles from TR-alpha(1)-deficient mice compared with their wild-type controls. TR-beta-deficient mice, which have high thyroid hormone levels, were less fatigue resistant than their wild-type controls, but contraction and relaxation times were not different. Western blot analyses showed a reduced concentration of the fast-type sarcoplasmic reticulum Ca(2+)-ATPase (SERCa1) in TR-alpha(1)-deficient mice, but no changes were observed in TR-beta-deficient mice compared with their respective controls. We conclude that in skeletal muscle, both TR-alpha(1) and TR-beta are required to get a normal thyroid hormone response.

Animals↗

Transient but not permanent neonatal diabetes mellitus is associated with paternal uniparental isodisomy of chromosome 6.

OBJECTIVES: The factors determining the pathogenesis of transient and permanent neonatal diabetes mellitus are poorly characterized. The purpose of this study was to examine the role of chromosome 6 in the pathogenesis of neonatal diabetes mellitus and to detect differences between these 2 phenotypes. METHODS: Microsatellite markers (D6S334, D6S286, D6S310, D6S308, D6S292, D6S311, and D6S403) and human leukocyte antigen DQ alleles were examined using polymerase chain reaction and DNA fragment electrophoresis in 3 patients with transient and 3 patients with permanent neonatal diabetes mellitus. Humoral markers of islet cell autoimmunity and clinical characteristics were analyzed in the 2 groups. RESULTS: A patient with transient neonatal diabetes mellitus (TND) and macroglossia carrying paternal uniparental isodisomy (UPD) of chromosome 6 has been identified. The isodisomy affected the whole chromosome; no maternal chromosome 6 sequences were detected. The permanent neonatal diabetes mellitus cases and the other 2 cases with TND did not have UPD. None of the patients had high-risk type 1 diabetes human leukocyte antigen DQ alleles and most infants were negative for islet cell-specific autoantibodies indicating that none of the 2 forms of neonatal diabetes mellitus is likely to be of autoimmune origin. An association of TND and persistent granulocytopenia is described for the first time. CONCLUSIONS: We propose that transient and permanent forms of neonatal diabetes mellitus have different genetic background and represent different disease entities. TND is associated with UPD of chromosome 6 suggesting that an imprinted gene on chromosome 6 is responsible for this phenotype. It seems that 2 copies of the paternal allele are necessary for the development of TND; therefore, it is likely that overexpression of a putative gene located on chromosome 6 alters pancreatic beta-cell maturation and insulin secretion.

Chromosomes, Human, Pair 6↗

Undergraduate medical education: tendencies and requirements in a rapidly developing Europe.

This study pinpoints the necessity to constantly monitor local approaches in undergraduate medical education on an inter-European scale. Traditional undergraduate medical curricula need restructuring to account for the increasing amount of medical knowledge and rapid changes and developments in societies, nosology, therapy and IT. European undergraduate medical curricula should be harmonized not egalized, with a focus on inter-European sharing of resources, mobility, credit (allocation, accumulation and transfer), definition of European and trans-European mission statements, identification of quality metrics, advice on dealing with conflicting aims such as specialization and generalization, on communicating core knowledge instead of providing overabundance of information, and on introducing multifaceted teaching and learning methods, as well as providing strategies for life long learning. Sound medical education can no longer and nowhere be considered under the autonomous auspices of individual Medical Schools or national philosophies. It has to be perceived and structured as a competitive and flexible approach which promotes life long learning of teachers, students, physicians and other related staff with international awareness. It is stressed that student and staff mobility, as well as virtual mobility in the form of worldwide available teaching modules and expertise have to be incorporated into national medical curricula. This is to guarantee up-to-date education in support of patient demands, future professionality and competitiveness of students, physicians and Public Health System institutions. The formal approaches of traditional subject related curricula as well as problem based learning must be linked with quality approved state of the art ODL, evaluated international CME strategies and training in the utilization of IT in preparation of lifelong learning. Strategies for the use of IT need updating on a regular basis to diminish the gap between undergraduate and postgraduate medical education. General European perspectives of medical education are discussed in relation to ECTS, ODL, compulsory credited and evaluated CME and relicensing of physicians. Prime features of ETM--the most reputed and well-known European medical CME initiative fostering quality assured international awareness are described and recommended for local and nationwide implementation. Specific links of the Bonn undergraduate medical curriculum with credited and evaluated CME and imminent European strategies are detailed. The authors conclude that European universities not adapting at least some of the outlined curricular necessities will rapidly lose their competitiveness compared to other national and international Medical Schools. Harmonized European ethical mission statements and consequent utilization of IT deserve special considerations in this context.

Computer-Assisted Instruction↗

[Use of new materials results in improved prostheses. Metals, polymers, ceramics and composite materials extend durability].

Advances in our knowledge of multifactorial host-biomaterial interactions have improved the outcome of joint replacement surgery. Fixation and aseptic loosening are the principal foci of research. Wear debris from articulating parts is a major cause of prosthetic loosening. Tri-biological analysis, and the development of new materials and surface finishes have reduced wear particle production. The use of modular implants increases flexibility and facilitates surgical fit, but also introduces new problems such as dissociation of components, corrosion and wear. In the future, as design, biomaterials and surgical technique become further optimized, arthroplasty may also become an alternative for use in younger patients.

Arthroplasty, Replacement↗

NMR characterization of the NADP(H)-binding domain of Escherichia coli transhydrogenase: sequential assignment and global fold.

The soluble NADP(H)-binding domain of Escherichia coli transhydrogenase (186 amino acids, 20.4 kDa, rotational correlation time 14 ns) was characterized using NMR techniques. The global fold is similar to that of a classical dinucleotide-binding fold with six parallel beta-strands in a central sheet surrounded by helices and irregular structures, but is lacking both alphaD and alphaE. The substrate is bound in an extended conformation at the C-terminal end of the parallel beta-sheet and our data support the notion of a redox dependent structural rearrangement.

Amino Acid Sequence↗

Changes in neuropeptide Y receptors and pro-opiomelanocortin in the anorexia (anx/anx) mouse hypothalamus.

The pro-opiomelanocortinergic (POMCergic) system originating in the hypothalamic arcuate nucleus extends projections widely over the brain and has been shown to be intricately linked and parallel to the arcuate neuropeptide Y (NPY) system. Both NPY and POMC-derived peptides (melanocortins) have been strongly implicated in the control of feeding behavior, with the former exerting orexigenic effects and the latter having anorexigenic properties. Mice homozygous for the lethal anorexia (anx) mutation are hypophagic, emaciated, and exhibit anomalous processing of NPY exclusively in the arcuate nucleus, providing an interesting model to study NPY-POMC interactions. In the present study, several morphological markers were used to investigate the histochemistry and morphology of the POMC system in anx/anx mice. In situ hybridization demonstrated decreased numbers of POMC mRNA-expressing neurons in the anx/anx arcuate nucleus. In parallel, mRNA levels for both the NPY Y1 and Y5 receptors, which are expressed in POMC neurons, were decreased. Also, expression of the NPY Y2 autoreceptor was attenuated. Immunohistochemistry using antibodies against adrenocorticotropic hormone to demonstrate POMC cell bodies, against alpha-melanocyte-stimulating hormone to demonstrate axonal projections and against the NPY Y1 receptor to demonstrate dendritic arborizations, showed strikingly decreased immunoreactivities for all these markers. The present data suggest that degeneration of the arcuate POMC system is a feature characteristic of the anx/anx mouse. The possible relationship to the NPYergic phenotype of this animal is discussed.

Adrenocorticotropic Hormone↗

[New materials improve joint prostheses. Metals, polymers, ceramics and composite materials extend the durability].

Advances in our knowledge of multfactorial host-biomaterial interactions have improved the outcome of joint replacement surgery. Fixation and aseptic loosening are the principal foci of research. Wear debris from articulating parts is a major cause of prosthetic loosening. Tribological analysis, and the development of new materials and surface finishes have reduced wear particle production. The use of modular implants increases flexibility and facilitates surgical fit, but also introduces new problems such as dissociation of components, corrosion and wear. In the future, as design, biomaterials and surgical technique become further optimised, arthroplasty may also become an alternative for use in younger patients.

Animals↗

Endocrine and behavioral traits in low-avoidance Sprague-Dawley rats.

In the present series of experiments, we have examined the endocrine profile of two stable colonies of Sprague-Dawley rats, here labeled Stock A, and Stock B, differing markedly in their ability to acquire a conditioned avoidance response. On separate occasions, the animals were subjected to five daily sessions (approximately 20 trials per 15 min session) of conditioned avoidance training, measurements of startle reactivity to an auditory stimulation and open-field spontaneous locomotor activity observations. The experiments were concluded by taking blood samples for later analysis of plasma glucose and plasma levels of the following hormones: insulin, gastrin, CCK, glucagon, somatostatin, oxytocin and corticosterone. The low-performing Stock B animals were characterized by [1] being more reactive to sensory stimulation: higher startle amplitude and shorter startle latency; [2] having higher plasma insulin and corticosterone levels, whereas plasma gastrin and oxytocin were significantly lowered and a strong tendency for a decrease also in plasma CCK. There were no differences in spontaneous locomotor activity between the two substrains. Taking total variability in avoidance performance into account, there was a statistically significant positive correlation between plasma oxytocin, as well as gastrin, levels and avoidance performance. The evidence obtained here, and in other laboratories, suggests that the Stock B animals display hormonal changes indicative of a submissive-defensive reaction pattern. Thus, the avoidance acquisition deficits displayed by the present Sprague-Dawley stocks A and B, are in all probability caused by emotional reactions when challenged with external stimuli requiring active responding.

Acoustic Stimulation↗

Mapping of residues in the NADP(H)-binding site of proton-translocating nicotinamide nucleotide transhydrogenase from Escherichia coli. A study of structure and function.

Conformational changes in proton pumping transhydrogenases have been suggested to be dependent on binding of NADP(H) and the redox state of this substrate. Based on a detailed amino acid sequence analysis, it is argued that a classical betaalphabetaalphabeta dinucleotide binding fold is responsible for binding NADP(H). A model defining betaA, alphaB, betaB, betaD, and betaE of this domain is presented. To test this model, four single cysteine mutants (cfbetaA348C, cfbetaA390C, cfbetaK424C, and cfbetaR425C) were introduced into a functional cysteine-free transhydrogenase. Also, five cysteine mutants were constructed in the isolated domain III of Escherichia coli transhydrogenase (ecIIIH345C, ecIIIA348C, ecIIIR350C, ecIIID392C, and ecIIIK424C). In addition to kinetic characterizations, effects of sulfhydryl-specific labeling with N-ethylmaleimide, 2-(4'-maleimidylanilino)naphthalene-6-sulfonic acid, and diazotized 3-aminopyridine adenine dinucleotide (phosphate) were examined. The results are consistent with the view that, in agreement with the model, beta-Ala348, beta-Arg350, beta-Ala390, beta-Asp392, and beta-Lys424 are located in or close to the NADP(H) site. More specifically, beta-Ala348 succeeds betaB. The remarkable reactivity of betaR350C toward NNADP suggests that this residue is close to the nicotinamide moiety of NADP(H). beta-Ala390 and beta-Asp392 terminate or succeed betaD, and are thus, together with the region following betaA, creating the switch point crevice where NADP(H) binds. beta-Asp392 is particularly important for the substrate affinity, but it could also have a more complex role in the coupling mechanism for transhydrogenase.

Amino Acid Sequence↗