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Biomedical subjects

K Johansson

Publications and source records attributed to K Johansson.

At least 55 records · Page 3Linked to original sources

Structural basis for light activation of a chloroplast enzyme: the structure of sorghum NADP-malate dehydrogenase in its oxidized form.

Some key chloroplast enzymes are activated by light via a ferredoxin-thioredoxin reduction system which reduces disulfide bridges in the enzymes. We describe for the first time the structural basis for the redox activation of a chloroplast enzyme, the NADP-dependent malate dehydrogenase (MDH) from Sorghum vulgare whose structure has been determined and refined at 2.4 A resolution. In addition to the normal structural components of MDHs, the enzyme exhibits extensions at both the N- and C-termini, each of which contains a regulatory disulfide bridge which must be reduced for activation. The N-terminal disulfide motif is inserted in a cleft between the two subunits of the dimer, thereby locking the domains in each subunit. The C-terminal disulfide keeps the C-terminal residues tight to the enzyme surface and blocks access to the active site. Reduction of the N-terminal disulfide would release the stopper between the domains and give the enzyme the necessary flexibility. Simultaneous reduction of the C-terminal disulfide would free the C-terminal residues from binding to the enzyme and make the active site accessible.

Amino Acid Sequence↗

The effect of uvulopalatopharyngoplasty without tonsillectomy using local anaesthesia: a prospective long-term follow-up.

This paper presents the long-term effect of restricted surgery for snoring and sleep apnoea. Patients with obstructive sleep apnoea (OSAS) (19) or heavy snoring (HS) (36) were studied prospectively for five to seven years after uvulopalatopharyngoplasty without tonsillectomy performed by regular surgical technique using local anaesthesia (LUPP). Five years after surgery, 90 per cent answered a questionnaire. All OSAS patients were offered a polysomnography, and the HS patients were offered a sleep study. Eighty per cent still showed a positive effect on daytime somnolence, and 77 per cent on snoring. Side-effects were reported by 40 per cent; most common was choking (20 per cent) the first year. Eighteen per cent had local problems such as globus sensation. The polysomnography showed that 80 per cent were still 'responders' with an apnoea index (AI) reduction of > 50 per cent. None of the HS patients had developed OSAS. In conclusion, LUPP in selected patients with OSAS or HS has a good long-term effect. Side-effects are common, but diminish with time.

Airway Obstruction↗

Prospective study of symptoms and gastro-oesophageal reflux 10 years after posterior partial fundoplication.

BACKGROUND: This was a prospective study of symptoms, and short-term and long-term reflux competence after partial fundoplication. METHODS: Some 101 patients were operated consecutively with posterior partial (270 degrees ) fundoplication. Indications for surgery were reflux disease without erosive oesophagitis in 25 patients, moderate oesophagitis in 43, severe oesophagitis in 25 and paraoesophageal hernia in eight. Symptom score, manometry and pH tests were performed before operation, 6 months after operation and after 6-14 years. RESULTS: All patients (n = 101) were free from heartburn and regurgitation at early follow-up. There was evidence of clinical recurrence at late follow-up (n = 87) in two of 22 patients without oesophagitis before operation, two of 39 with moderate oesophagitis before operation and three of 19 patients with severe oesophagitis before operation; 92 per cent had good reflux control at late follow-up. CONCLUSION: Posterior partial fundoplication shows excellent reflux control at early follow-up. Ten years later fewer than 10 per cent of patients have recurrence, which is more common in patients who had severe oesophagitis before operation.

Adult↗

Inbreeding and inbreeding depression on reproduction and production traits of White Leghorn lines selected for egg production traits.

1. The rate of inbreeding and its effect on reproduction and egg production traits were studied in White Leghorn lines selected for egg production traits. The experiment was carried out for 10 generations in a control line (C) and in lines selected for increased egg number (EN), egg weight (EW) and egg mass (EM). 2. Data were available on reproduction traits, such as percent fertile eggs (PF), percent hatched of fertile eggs (PHF) and percent hatched of total eggs set (PHT), and on egg production traits such as age at 1st egg (AFE), egg number and egg weight. 3. The rate of increase in average inbreeding per generation was 1.50, 1.24, 1.14 and 0.18% for the line EN, EW, EM and C, respectively. The effect of inbreeding on reproduction and production traits was estimated by including the inbreeding coefficient of the hen (Fh), embryo (Fe) and mate (Fs) as a partial linear regression in the model. 4. There was a significant effect of inbreeding on reproduction traits in line EW attributable to the inbreeding of the hen, embryo and mate. No such effect was observed in the other lines. 5. In all lines inbreeding tended to reduce egg number and delay sexual maturity. In general, all lines reacted differently to inbreeding.

Animals↗

Single-step divergent selection for male comb shape in two White Leghorn lines.

1. Divergent selection for comb shape (SH, the way that the cockerel bears the comb) was performed in 2 White Leghorn lines in a study aimed at assessing possibilities for improving SH. 2. Line A, selected for large comb size (CS) at 29 weeks of age, had great SH problems whereas Line H, selected for high hyaluronic acid concentration in the comb (HA), had minor SH problems. Multivariate analyses were used to estimate genetic parameters for SH, CS and HA in lines A and H and in a control line (C). 3. Significant direct selection responses for SH were achieved in both lines. There were significant unfavourable correlated responses for CS in both lines. 4. The correlated responses for HA were not significant and were unfavourable in Line A and favourable in Line H. 5. Heritabilities for SH and CS were high in both lines and relatively low for HA. Most of the genetic correlations were in agreement with the correlated responses obtained.

Animals↗

Attitudes toward management of patients with subacromial pain in Swedish primary care.

OBJECTIVE: We aimed to describe the attitudes among GPs and physiotherapists toward the diagnostic approach and management of patients with a common shoulder disorder. METHOD: A questionnaire was sent out to 188 GPs and 71 physiotherapists. The total response rate was 71.8%. The questions were based on a written case simulation with cues about history and symptoms. RESULTS: The results showed a unanimous opinion of the diagnosis. Rotator cuff tendinitis was marked as the most probable. The two groups showed similarities in the way that they would examine the patient. The GPs referred the patients to the physiotherapists significantly more often than the other way around. The most probable choice of treatment made by the GPs was non-steroidal anti-inflammatory drugs (NSAIDs) and by the physiotherapists, movement exercises together with ergonomics. Most treatment alternatives had at least 20% of the responders marking a neutral attitude, and few treatments were disregarded. CONCLUSIONS: We conclude that in Swedish primary care GPs and physiotherapists have a uniform diagnostic approach towards patients with subacromial pain, but their choice of treatment reflects an uncertainty about the effectiveness of conservative treatments. The questioned pathogenesis of the suggested diagnosis and lack of research regarding the efficacy of conservative treatments could explain this uncertainty.

Adult↗

Morphological and biochemical investigation of nitric oxide synthase and related enzymes in the rat and pig urothelium.

We investigated the enzymes involved in the NADPH-diaphorase (d) reaction in the rat and pig bladder urothelium. The urothelial cell layer displayed intense and uniform NADPH-d activity. Preincubation with the flavoprotein inhibitor diphenyleneiodionium chloride (DPI) and the alkaline phosphatase inhibitor levamisole concentration-dependently decreased the urothelial NADPH-d activity. Immunoreactivities to neuronal (n), endothelial (e), or inducible (i) nitric oxide synthase (NOS) were not detected in rat or pig urothelial cells. In rats, the urothelium was uniformly immunoreactive for NADPH cytochrome P450 reductase, whereas the pig urothelium displayed inconsistent labeling. In lipopolysaccharide (LPS)-treated rats, the bladder urothelium showed positive iNOS immunoreactivity. The iNOS labeling was found predominantly in cells located in the basal layer of the urothelium. In the pig bladder mucosa, a Ca2+-dependent NOS activity was evident in cytosolic and particulate fractions that was quantitatively comparable to the NOS activity found in the smooth muscle. In ultrastructural studies of urothelial cells, NADPH-d reaction products were found predominantly on membranes of the nuclear envelope, endoplasmatic reticulum and mitochondria. In conclusion, NADPH-d staining of the urothelium cannot be taken as an indicator for the presence of constitutively expressed NOS. Activity of alkaline phosphatase and cytochrome P450 reductase may account for part of the NADPH-d reaction in urothelial cells. However, LPS treatment of rats caused expression of iNOS in urothelial cells.

Animals↗

Bayesian analysis of birth weight and litter size in Baluchi sheep using Gibbs sampling.

Variance and covariance components for birth weight (BWT), as a lamb trait, and litter size measured on ewes in the first, second, and third parities (LS1 through LS3) were estimated using a Bayesian application of the Gibbs sampler. Data came from Baluchi sheep born between 1966 and 1989 at the Abbasabad sheep breeding station, located northeast of Mashhad, Iran. There were 10,406 records of BWT recorded for all ewe lambs and for ram lambs that later became sires or maternal grandsires. All lambs that later became dams had records of LS1 through LS3. Separate bivariate analyses were done for each combination of BWT and one of the three variables LS1 through LS3. The Gibbs sampler with data augmentation was used to draw samples from the marginal posterior distribution for sire, maternal grandsire, and residual variances and the covariance between the sire and maternal grandsire for BWT, variances for the sire and residual variances for the litter size traits, and the covariances between sire effects for different trait combinations, sire and maternal grandsire effects for different combinations of BWT and LS1 through LS3, and the residual covariations between traits. Although most of the densities of estimates were slightly skewed, they seemed to fit the normal distribution well, because the mean, mode, and median were similar. Direct and maternal heritabilities for BWT were relatively high with marginal posterior modes of .14 and .13, respectively. The average of the three direct-maternal genetic correlation estimates for BWT was low, .10, but had a high standard deviation. Heritability increased from LS1 to LS3 and was relatively high, .29 to .37. Direct genetic correlations between BWT and LS1 and between BWT and LS3 were negative, -.32 and -.43, respectively. Otherwise, the same correlation between BWT and LS2 was positive and low, .06. Genetic correlations between maternal effects for BWT and direct effects for LS1 through LS3 were all highly negative and consistent for all parities, circa -.75. Environmental correlations between BWT and LS1 through LS3 were relatively low and ranged from .18 to .29 and had high standard errors.

Animal Husbandry↗

"Quasi-REML" correlation estimates between production and health traits in the presence of selection and confounding: a simulation study.

Performance of the "quasi-REML" method for estimating correlations between a continuous trait and a categorical trait, and between two categorical traits, was studied with Monte Carlo simulations. Three continuous, correlated traits were simulated for identical populations and three scenarios with either no selection, selection for one moderately heritable trait (Trait 1, h2 = .25), and selection for the same trait plus confounding between sires and management groups. The "true" environmental correlations between Traits 2 (h2 = .10) and 3 (h2 = .05) were always of the same absolute size (.20), but further data scenarios were generated by setting the sign of environmental correlation to either positive or negative. Observations for Traits 2 and 3 were then reassigned to binomial categories to simulate health or reproductive traits with incidences of 15 and 5%, respectively. Genetic correlations (r(g12), r(g13), and r(g23) and environmental correlations (r(e12), r(e13), and r(e23)) were estimated for the underlying continuous scale (REML) and the visible categorical scales ("quasi-REML") with linear multiple-trait sire and animal models. Contrary to theory, practically all "quasi-REML" genetic correlations were underestimated to some extent with the sire and animal models. Selection inflated this negative bias for sire model estimates, and the sign of r(e23) noticeably affected r(g23) estimates for the animal model, with greater bias and SD for estimates when the "true" r(e23) was positive. Transformed "quasi-REML" environmental correlations between a continuous and a categorical trait were estimated with good efficiency and little bias, and corresponding correlations between two categorical traits were systematically overestimated. Confounding between sires and contemporary groups negatively affected all correlation estimates on the underlying and the visible scales, especially for sire model "quasi-REML" estimates of genetic correlation. Selection, data structure, and the (co)variance structure influences how well correlations involving categorical traits are estimated with "quasi-REML" methods.

Animal Husbandry↗

Effects of compression bandaging with or without manual lymph drainage treatment in patients with postoperative arm lymphedema.

We examined the effects of low stretch compression bandaging (CB) alone or in combination with manual lymph drainage (MLD) in 38 female patients with arm lymphedema after treatment for breast cancer. After CB therapy for 2 weeks (Part I), the patients were allocated to either CB or CB + MLD for 1 week (Part II). Arm volume and subjective assessments of pain, heaviness and tension were measured. The mean lymphedema volume reduction for the total group during Part I was 188 ml (p < 0.001), a mean reduction of 26% (p < 0.001). During Part II the volume reduction in the CB + MLD group was 47 ml (p < 0.001) and in CB group 20 ml. These differences were not significant (p = 0.07). A percentage reduction of 11% (p < 0.001) in the CB + MLD group and 4% in the CB group was significantly different (p = 0.04). In both the CB and the CB + MLD group, a decrease of feeling of heaviness (p < 0.006 and p < 0.001, respectively) and tension (p < 0.001 for both) in the arm was found, but only the CB + MLD group showed decreased pain (p < 0.03). Low stretch compression bandaging is an effective treatment giving volume reduction of slight or moderate arm lymphedema in women treated for breast cancer. Manual lymph drainage adds a positive effect.

Adult↗

Long-term full-thickness embryonic rabbit retinal transplants.

PURPOSE: To establish the light and electron microscopic morphology of long-term full-thickness embryonic rabbit retinal transplants, with special attention paid to graft- host integration. METHODS: Eighteen rabbits received a complete embryonic neuroretina 19 days after conception. The transplants were positioned under the host retina, flat against the host retinal pigment epithelium with proper polarity, using a vitrectomy technique. After surviving 3 to 10 months, the transplants were examined by light and electron microscopy. RESULTS: The outer retina of the host had degenerated in all specimens. In 16 of the 18 eyes, well-laminated transplants with correct polarity, measuring up to 3.2 mm in length, were found. The transplants displayed long outer segments facing the host retinal pigment epithelium, and they were laminated to the level of the inner plexiform layer in which fusion with the host was often evident. Fusion was more prominent in the oldest transplants. Electron microscopy revealed bundles of neurites at different levels of maturation in close contact with Müller cell fimbriae at regular intervals along the graft-host border. CONCLUSIONS: Full-thickness embryonic rabbit retinal transplants positioned with correct polarity develop into large laminated retinas and survive without immunosuppression for at least 10 months. Host and graft adapt and almost reconstruct the normal retinal appearance. Ultrastructurally, well-developed photoreceptors and many normal synapse types are seen, and neuron sprouting is evident at the graft-host border.

Animals↗

The autoinhibition of sorghum NADP malate dehydrogenase is mediated by a C-terminal negative charge.

The chloroplastic NADP malate dehydrogenase is completely inactive in its oxidized form and is activated by thiol/disulfide interchange with reduced thioredoxin. To elucidate the molecular mechanism underlying the absence of activity of the oxidized enzyme, we used site-directed mutagenesis to delete or substitute the two most C-terminal residues (C-terminal Val, penultimate Glu, both bearing negative charges). We also combined these mutations with the elimination of one or both of the possible regulatory N-terminal disulfides by mutating the corresponding cysteines. Proteins mutated at the C-terminal residues had no activity in the oxidized form but were partially inhibited when pretreated with the histidine-specific reagent diethyl pyrocarbonate before activation, showing that the active site was partially accessible. Proteins missing both N-terminal regulatory disulfides reached almost full activity without activation upon elimination of the negative charge of the penultimate Glu. These results strongly support a model where the C-terminal extension is docked into the active site through a negatively charged residue, acting as an internal inhibitor. They show also that the reduction of both N-terminal bridges is necessary to release the C-terminal extension from the active site. This is the first report for a thiol-activated enzyme of a regulatory mechanism resembling the well known intrasteric inhibition of protein kinases.

Amino Acid Substitution↗

Alzheimer changes are common in aged drivers killed in single car crashes and at intersections.

With increasing age, diseases affecting the cognitive functions are more frequent. These diseases may increase the risk for fatal car crashes. We analyzed the frequency of neuropathological alterations characteristic of Alzheimer's disease (i.e. neuritic and diffuse plaques, and neurofibrillary tangles) in two association areas of the brain, parietal and frontal cerebral cortex, from 98 fatally injured aged drivers. In the age groups of 65-75 and over 75 years of age, 50% and 72% of the drivers, respectively, had neuritic plaques in either parietal and/or frontal cortex. In 14% of all killed drivers the number of neuritic plaques reached the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) age-related histologic score C, which indicates the diagnosis of Alzheimer's disease (AD), and an additional 33% had score B, which suggests the diagnosis of AD. Neuropathological AD changes were most common in the brains of drivers killed in single vehicle crashes, followed by multivehicle crashes at intersections and least common in multivehicle crashes elsewhere, but the differences did not reach statistical significance. In a great majority (80-85%) of cases the killed aged driver was the guilty party of the crash. The results imply, that incipient AD may contribute to fatal crashes of aged drivers, and therefore the forensic autopsy of these victims should include neuropathological examination.

Accidents, Traffic↗

Correlations between cholinergic neurons and muscarinic m2 receptors in the rat retina.

Acetylcholine is well established as the neurotransmitter of starburst amacrine cells in the vertebrate retina but their function is poorly understood. We compared the distribution of muscarinic m2 receptors in the rat retina with the localization of the starburst cell processes. mAChR2 immunoreactivity appeared in a central band in the inner plexiform layer, which did not co-localize with the processes of the cholinergic amacrine cells. We found co-labelling of VAChT and ChAT making it highly unlikely that there are undetected cholinergic neurons in rat retina. Most mAChR2 receptors were located far from the cholinergic neurons, suggesting that most of them are unlikely to be associated with conventional cholinergic synapses.

Acetylcholine↗

[Genetic factors are often found inl Alzheimer disease. An extensive twin study to clarify the heredity-environment relationship].

Genetic and environmental risk factors are central concerns in dementia research. Through twin studies one can study the relative importance of genetic and environmental risk factors. One such study, based on the Swedish Twin Registry, shows that genetic effects are of considerable importance for developing Alzheimer's disease, even late in life, but that environmental factors are also important. For vascular dementia, the results indicate that non-genetic factors are of primary importance.

Aged↗

Structure of betaine aldehyde dehydrogenase at 2.1 A resolution.

The three-dimensional structure of betaine aldehyde dehydrogenase, the most abundant aldehyde dehydrogenase (ALDH) of cod liver, has been determined at 2.1 A resolution by the X-ray crystallographic method of molecular replacement. This enzyme represents a novel structure of the highly multiple ALDH, with at least 12 distinct classes in humans. This betaine ALDH of class 9 is different from the two recently determined ALDH structures (classes 2 and 3). Like these, the betaine ALDH structure has three domains, one coenzyme binding domain, one catalytic domain, and one oligomerization domain. Crystals grown in the presence or absence of NAD+ have very similar structures and no significant conformational change occurs upon coenzyme binding. This is probably due to the tight interactions between domains within the subunit and between subunits in the tetramer. The oligomerization domains link the catalytic domains together into two 20-stranded pleated sheet structures. The overall structure is similar to that of the tetrameric bovine class 2 and dimeric rat class 3 ALDH, but the coenzyme binding with the nicotinamide in anti conformation, resembles that of class 2 rather than of class 3.

Aldehyde Oxidoreductases↗

Impairments of some cognitive functions are common in crash-involved older drivers.

The relationship between limitations in different cognitive functions, measured with a neuropsychological test battery, and moving traffic violations among older drivers was investigated. Thirty-seven drivers aged 65 years or more, with temporarily suspended driving licenses (suspended drivers) were identified 23 were crash-involved and 14 were not. When compared to 31 controls with clean driving records, crash-involved suspended drivers performed less well on tests of visuoconstructive ability (p = 0.008), psychomotor speed (p = 0.019) and visuospatial memory (p = 0.036). Non-crash-involved suspended drivers did not differ from controls. A combination of three tests (of visuoconstructive ability, visuospatial memory and verbal episodic memory) succeeded in correctly classifying 65.2% of the crash-involved suspended drivers. The results support the idea of cognitive decrements as an important causal factor in crashes of older drivers.

Accidents, Traffic↗