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Biomedical subjects

Michael Larsen

Publications and source records attributed to Michael Larsen.

At least 37 records · Page 2Linked to original sources
PubMed2005

The multifocal ERG in diabetic patients without retinopathy during euglycemic clamping.

PURPOSE: Prolonged multifocal electroretinogram (mfERG) implicit times have been observed in diabetes, although the acute response to hyperglycemia is an acceleration of the ERG. The hypothesis for the current investigation was that this discrepancy is caused by a protracted adaptational response of the retina to hyperglycemia. METHODS: Fourteen patients with type 1 diabetes without retinopathy were blood glucose clamped at 5 mM for 75 minutes before the recording of the mfERG. The results were compared with those found in 14 age-matched healthy subjects. RESULTS: During acute normoglycemia, patients with type 1 diabetes without retinopathy demonstrated an overall 1.36-ms delay of the P1 first-order implicit times (P = 0.0013) and a 0.72-ms delay of the second-order P1 (P = 0.0049) compared with healthy subjects at 4.9 +/- 0.28 mM blood glucose. During acute hyperglycemia, the P1 first-order delay was only 0.81 ms (P = 0.02), and the P1 second-order implicit time was comparable to that of healthy subjects (P > 0.05). The magnitude of the diabetes-associated implicit time delay, at both levels of glycemia, was proportional to the level of chronic hyperglycemia at study entry, as expressed by the patients' HbA1c. CONCLUSIONS: During acute normoglycemia, patients with type 1 diabetes without retinopathy demonstrated a delayed mfERG response compared with the healthy subjects. The delay was more pronounced during euglycemia than during hyperglycemia, and at both levels of glycemia, the delay was proportional to the patients' habitual hyperglycemia. The results show that chronic hyperglycemia induces an adaptational response that tends to normalize retinal implicit times at a higher level of habitual glycemia.

Adult↗
PubMed2005

Effect of ruboxistaurin on blood-retinal barrier permeability in relation to severity of leakage in diabetic macular edema.

PURPOSE: The purpose of the study was to investigate the effect of orally administered ruboxistaurin (RBX, LY333531), a selective protein kinase C beta inhibitor, on the permeability of the blood-retinal barrier in patients with diabetic macular edema. METHODS: Forty-one patients with diabetic macular edema were randomly assigned to an 18-month randomized, placebo-controlled, double-masked trial including four study arms (4, 16, or 32 mg/d RBX, or placebo). The RBX group comprised 30 patients (42 eyes) and the placebo group 11 patients (13 eyes). Retinal vascular leakage was assessed using vitreous fluorometry at baseline and after 3, 12, and 18 months. Statistical analysis of the effect of treatment accounted for repeated measurements and tested potential interaction with baseline permeability, HbA(1c), and arterial blood pressure. RESULTS: Statistical analysis and modeling demonstrated a significant interaction between RBX treatment at any dosage and baseline permeability (P = 0.032, mixed models). A threefold or higher increase in retinal vascular leakage at baseline was associated with a significant reduction (30%) in retinal vascular leakage after RBX treatment compared with placebo. Visual acuity was normal at baseline and remained unchanged throughout the study. CONCLUSIONS: RBX treatment was associated with a reduction of retinal vascular leakage in eyes that had diabetic macular edema and markedly elevated leakage at baseline. These data suggest that clinical benefit from RBX treatment may be most prominent in patients with severe macular edema at baseline, and trials investigating this therapy may benefit from stratification according to baseline leakage.

Administration, Oral↗
PubMed2005

Heritability of cilioretinal arteries: a twin study.

PURPOSE: To determine whether the presence of one or more cilioretinal arteries, a distinct element of the pattern of fundus vessels, is genetically programmed, influenced by environmental factors, or the result of random mechanisms of vascular development. METHODS: The fundi of 112 pairs of healthy monozygotic and dizygotic twins were examined using digital fundus photography and visual assessment of grayscale fundus photographs and color transparencies to detect the presence of cilioretinal arteries. RESULTS: Cilioretinal arteries were present in 45.1% of participants and 28.8% of eyes. The majority of cilioretinal arteries, 88.2%, were located temporally, and 11.8% were located nasally. Monozygotic twins had higher concordance rates for cilioretinal arteries than dizygotic twins. Tetrachoric correlations and Mantel-Haenszel odds ratios demonstrated statistically significant evidence of a genetic effect underlying the presence of cilioretinal arteries (P < 0.01). Statistical analysis supported the hypothesis that additive genetic factors influenced the presence of cilioretinal arteries with a heritability of 71.4%, the remaining variance being attributable to nonshared or random environmental factors. CONCLUSIONS: The presence or absence of one or more cilioretinal arteries in healthy persons is markedly influenced by genetic factors.

Adult↗
PubMed2004

MiRP1 modulates HCN2 channel expression and gating in cardiac myocytes.

MinK-related protein (MiRP1 or KCNE2) interacts with the hyperpolarization-activated, cyclic nucleotide-gated (HCN) family of pacemaker channels to alter channel gating in heterologous expression systems. Given the high expression levels of MiRP1 and HCN subunits in the cardiac sinoatrial node and the contribution of pacemaker channel function to impulse initiation in that tissue, such an interaction could be of considerable physiological significance. However, the functional evidence for MiRP1/HCN interactions in heterologous expression studies has been accompanied by inconsistencies between studies in terms of the specific effects on channel function. To evaluate the effect of MiRP1 on HCN expression and function in a physiological context, we used an adenovirus approach to overexpress a hemagglutinin (HA)-tagged MiRP1 (HAMiRP1) and HCN2 in neonatal rat ventricular myocytes, a cell type that expresses both MiRP1 and HCN2 message at low levels. HA-MiRP1 co-expression with HCN2 resulted in a 4-fold increase in maximal conductance of pacemaker currents compared with HCN2 expression alone. HCN2 activation and deactivation kinetics also changed, being significantly more rapid for voltages between -60 and -95 mV when HA-MiRP1 was co-expressed with HCN2. However, the voltage dependence of activation was not affected. Co-immunoprecipitation experiments demonstrated that expressed HA-MiRP1 and HCN2, as well as endogenous MiRP1 and HCN2, co-assemble in ventricular myocytes. The results indicate that MiRP1 acts as a beta subunit for HCN2 pacemaker channel subunits and alters channel gating at physiologically relevant voltages in cardiac cells.

Animals↗
PubMed2004

Visual acuity and refractive errors in a suburban Danish population: Inter99 Eye Study.

PURPOSE: The present study was performed as part of an epidemiological study, the Inter99 Eye Study. The aim of the study was to describe refractive errors and visual acuity (VA) in a suburban Danish population. METHODS: The Inter99 Eye Study comprised 970 subjects aged 30-60 years and included a random control group as well as groups at high risk for ischaemic heart disease and diabetes mellitus. The present study presents VAs and refractive data from the control group (n = 502). All subjects completed a detailed questionnaire and underwent a standardized general physical and ophthalmic examination including determination of best corrected VA and subjective refractioning. RESULTS: Visual acuity </= 0.05 was found in one eye of one subject and VA </= 0.3 in 11 eyes of 11 subjects. The main cause of reduced visual function was strabismic amblyopia. Myopia (</= - 0.5 D, spherical equivalent refraction) was present in 33.1% of right eyes of the total population but in 56.8% of subjects with a university degree. CONCLUSIONS: Strabismic amblyopia was a significant cause of unilateral visual impairment. Myopia was approximately twice as frequent in subjects with a university degree as in the remaining study population.

Adult↗
PubMed2004

Unilateral diabetic macular oedema secondary to central retinal vein congestion.

PURPOSE: To describe two cases of strictly unilateral diabetic retinopathy with macular edema where the precipitating factor appears to have been retinal venous congestion. METHODS: Retrospective interventional case study. RESULTS: Examination of fundus photographic records demonstrated generalized venous dilation in the affected eyes years in advance of the development of unilateral diabetic macular edema. Relentless progression of edema and visual loss followed despite retinal photocoagulation treatment and ultimately the affected eyes in both patients developed central retinal vein occlusion. The fellow eyes in both patients remained without retinopathy throughout the period of observation. CONCLUSION: The sequential and strictly unilateral appearance of retinal venous dilation, diabetic macular edema, and central retinal vein occlusion in diabetic patients without fellow-eye retinopathy suggests that venous congestion induced the progression from hyperglycemic insult to vascular injury in the affected eyes. Presumably, diabetes may cause retinal vascular dysfunction that results in little or no vascular damage unless venous congestion is present. This supports that venous congestion and increased sensitivity to congestion are important components of the pathogenesis of diabetic macular edema.

Diabetic Retinopathy↗
PubMed2004

Screening for diabetic retinopathy using a digital non-mydriatic camera compared with standard 35-mm stereo colour transparencies.

PURPOSE: To investigate the use of a digital non-mydriatic camera for determining the ETDRS clinical level of diabetic retinopathy, and to evaluate its use in a screening setting to appropriately determine the need for referral to an ophthalmologist (ETDRS level > or = 35). METHODS: A total of 83 patients with diabetes were photographed with and without pharmacological pupil dilation at an ophthalmology department using a digital non-mydriatic camera, obtaining two sets of five non-stereoscopic, 45 degree field images of each eye. ETDRS seven standard field, 35-mm stereoscopic colour fundus photographs were also obtained. A subgroup of 59 patients was photographed at an optician's shop using the digital non-mydriatic camera without pupil dilation. RESULTS: There was substantial agreement between the clinical level of diabetic retinopathy assessed from the 35-mm photographs and the digital images: the ophthalmology department (kappa = 0.76) with pupil dilation and (kappa = 0.66) without pupil dilation, respectively, and at the optician's (kappa = 0.60 without pupil dilation). With respect to the need for referral to an ophthalmologist, there was almost perfect agreement in the ophthalmology department (kappa = 0.88) with pupil dilation and (kappa = 0.84) without pupil dilation, respectively, and those taken at the optician's (kappa = 0.87 without pupil dilation). CONCLUSION: A digital non-mydriatic camera may be used in a screening situation to appropriately determine the need for referral to an ophthalmologist (ETDRS level > or = 35).

Adult↗
PubMed2004

Diabetic retinopathy screening using digital non-mydriatic fundus photography and automated image analysis.

PURPOSE: To investigate the use of automated image analysis for the detection of diabetic retinopathy (DR) in fundus photographs captured with and without pharmacological pupil dilation using a digital non-mydriatic camera. METHODS: A total of 83 patients (165 eyes) with type 1 or type 2 diabetes, representing the full spectrum of DR, were photographed with and without pharmacological pupil dilation using a digital non-mydriatic camera. Two sets of five overlapping, non-stereoscopic, 45-degree field images of each eye were obtained. All images were graded in a masked fashion by two readers according to ETDRS standards and disagreements were settled by an independent adjudicator. Automated detection of red lesions as well as image quality control was made: detection of a single red lesion or insufficient image quality was categorized as possible DR. RESULTS: At patient level, the automated red lesion detection and image quality control combined demonstrated a sensitivity of 89.9% and specificity of 85.7% in detecting DR when used on images captured without pupil dilation, and a sensitivity of 97.0% and specificity of 75.0% when used on images captured with pupil dilation. For moderate non-proliferative or more severe DR the sensitivity was 100% for images captured both with and without pupil dilation. CONCLUSION: Our results demonstrate that the described automated image analysis system, which detects the presence or absence of DR, can be used as a first-step screening tool in DR screening with considerable effectiveness.

Area Under Curve↗
PubMed2004

Effect of short-term hyperglycemia on multifocal electroretinogram in diabetic patients without retinopathy.

PURPOSE: To investigate the effect of variations in blood glucose level on the multifocal electroretinogram (mfERG) in patients with type 1 diabetes without retinopathy. METHODS: Fourteen patients were clamped sequentially and in random order at 5 and 15 mM blood glucose for 75 minutes on the same day. MfERG was recorded in one eye at each level of blood glucose level. RESULTS: Compared to euglycemia (5 mM), hyperglycemia was associated with an overall decrease in the implicit times and an increase in the amplitudes of the multifocal ERG. The effect of hyperglycemia on implicit time reached statistical significance for the summed first positive (P1) and second negative component (N2) of the first-order kernel (P = 0.0020 and 0.0005, respectively) and all components of the second-order kernel (P = 0.014, 0.0037, and 0034, respectively). These changes in the mfERG demonstrated no significant variation in relation to retinal location or long-term blood glucose level. CONCLUSIONS: Steady-state hyperglycemia induced shorter first- and second-order kernel implicit times in patients with type 1 diabetes without retinopathy. The effects of hyperglycemia were not significant with retinal location. These results support the hypothesis that hyperglycemia accelerates retinal metabolism.

Adult↗
PubMed2003

Evaluation of prevalence and clinical implications of anthelmintic resistance in gastrointestinal nematodes in goats.

OBJECTIVE: To determine prevalence of resistance to all anthelmintics that are commonly used to treat gastrointestinal nematodes (GINs) in goats. DESIGN: Prospective study. ANIMALS: 777 goats. PROCEDURE: On each farm, goats were assigned to 1 of 5 treatment groups: untreated controls, albendazole (20 mg/kg [9.0 mg/lb], p.o., once), ivermectin (0.4 mg/kg [0.18 mg/lb], p.o., once), levamisole (12 mg/kg [5.4 mg/lb], p.o., once), or moxidectin (0.4 mg/kg, p.o., once), except on 3 farms where albendazole was omitted. Fecal samples were collected 2 weeks after treatment for determination of fecal egg counts (FECs), and percentage reductions were calculated by comparing data from anthelmintic-treated and control groups. Nematode populations were categorized as susceptible, suspected resistant, or resistant by use of guidelines published by the World Association for the Advancement of Veterinary Parasitology. RESULTS: Resistance to albendazole was found on 14 of 15 farms, and resistance to ivermectin, levamisole, and moxidectin was found on 17, 6, and 1 of 18 farms, respectively. Suspected resistance to levamisole and moxidectin was found on 4 and 3 farms, respectively. Resistance to multiple anthelmintics (albendazole and ivermectin) was found on 14 of 15 farms and to albendazole, ivermectin, and levamisole on 5 of 15 farms. Mean overall FEC reduction percentages for albendazole, ivermectin, levamisole, and moxidectin were 67, 54, 94, and 99%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Anthelmintic resistance in GINs of goats is highly prevalent in the southern United States. The high prevalence of resistance to multiple anthelmintics emphasizes the need for reexamination of nematode control practices.

Albendazole↗
PubMed2003

Corneal fluorescence in relation to genetic and environmental factors: a twin study.

PURPOSE: Corneal fluorescence is believed to be caused by advanced glycation end products formed by non-enzymatic glycation on corneal proteins. The purpose of the present twin study was to examine whether the process is related to genetic or environmental factors. METHODS: Corneal fluorescence was measured in 59 monozygotic and 54 dizygotic twin pairs. The influences of genetic and environmental factors were estimated using structural equation modelling. RESULTS: Interindividual variation in corneal fluorescence was attributable to environmental factors, whereas the effect of genetic factors was of little or no significance. Corneal fluorescence correlated significantly with smoking habits (r = 0.38) and the 2-hour oral glucose tolerance test response (r = 0.27), and increased with age (p < 0.0001). CONCLUSION: Fluorophore accumulation in the cornea was attributable to age and environmental effects, of which smoking was the most conspicuous identifiable factor, although glucose was also of relevance. However, the greater part of interindividual variation in corneal fluorescence remains unexplained.

Adult↗
PubMed2003

Kinetics of retinal lipoprotein precipitation and elimination after closure of subretinal new vessels.

PURPOSE: To study the kinetics of retinal precipitation and elimination of lipoprotein in relation to photodynamic therapy of subretinal new vessels. METHODS: This was a retrospective observational study of subretinal precipitate before and after photodynamic therapy for subfoveal new vessels secondary to age-related macular degeneration in 14 eyes demonstrating precipitate at one or more visits, using digital red-free gray-scale fundus photography, intravenous fluorescein angiography, optical coherence tomography, and morphometric mapping. RESULTS: In 14 eyes of 14 patients, the area covered by lipoprotein precipitate increased from a mean of 0.54 optic disc areas (range, 0-2.61) before treatment to a mean of 0.65 optic disc areas (range, 0.01-3.04) at 45 d after treatment (P = 0.18). Eyes with a serous detachment at baseline, before the initial treatment (n = 10) demonstrated more treatment-related precipitation than eyes without a serous detachment at baseline (n = 4; P = 0.034). Two eyes with a large amount of precipitate and a long follow-up demonstrated net elimination of precipitate from approximately 100 days after the initial treatment, with uniexponential precipitate half-lives of 43 and 32 days. CONCLUSIONS: Photodynamic therapy for subfoveal new vessels may be associated with retinal precipitation of lipoprotein, presumably because early extraction of water and salts from the subretinal fluid increases the concentration of leaked plasma proteins. Despite reperfusion of the subretinal vessels, macromolecular leakage appears to cease within 100 days, indicating that functional maturation of the new vessels has occurred, with an associated decrease in pore size.

Aged↗
PubMed2003

Automated detection of diabetic retinopathy in a fundus photographic screening population.

PURPOSE: To evaluate the performance of an automated fundus photographic image-analysis algorithm in high-sensitivity and/or high-specificity segregation of patients with diabetes with untreated diabetic retinopathy from those without retinopathy. METHODS: This was a retrospective cross-sectional study of 260 consecutive nonphotocoagulated eyes in 137 diabetic patients attending routine photographic retinopathy screening. Mydriatic 60 degrees fundus photography on 35-mm color transparency film was used, with a single fovea-centered field. Routine grading was based on visual examination of slide-mounted transparencies. Reference grading was performed with specific emphasis on achieving high sensitivity. Computer-assisted automated red lesion detection was performed on digitized transparencies. RESULTS: When applied in a screening population comprising patients with diabetes with untreated diabetic retinopathy in any eye and patients with diabetes without retinopathy, the automated lesion detection correctly identified 90.1% of patients with retinopathy and 81.3% of patients without retinopathy. A per-eye analysis for methodological purposes demonstrated that the automated lesion detection could be adapted to simulate various visual evaluation strategies. When adapted at high sensitivity, the automated system demonstrated sensitivity at 93.1% and specificity at 71.6%. When adapted at high specificity the automated system demonstrated sensitivity at 76.4% and specificity at 96.6%, closely matching routine visual grading at sensitivity 76.4% and specificity 98.3%. CONCLUSIONS: Automated detection of untreated diabetic retinopathy in fundus photographs from a screening population of patients with diabetes can be made with adjustable priority settings, emphasizing high-sensitivity identification of diabetic retinopathy or high-specificity identification of absence of retinopathy, covering opposing extremes of visual evaluation strategies demonstrated by human observers.

Aneurysm↗
PubMed2003

Automated detection of fundus photographic red lesions in diabetic retinopathy.

PURPOSE: To compare a fundus image-analysis algorithm for automated detection of hemorrhages and microaneurysms with visual detection of retinopathy in patients with diabetes. METHODS: Four hundred fundus photographs (35-mm color transparencies) were obtained in 200 eyes of 100 patients with diabetes who were randomly selected from the Welsh Community Diabetic Retinopathy Study. A gold standard reference was defined by classifying each patient as having or not having diabetic retinopathy based on overall visual grading of the digitized transparencies. A single-lesion visual grading was made independently, comprising meticulous outlining of all single lesions in all photographs and used to develop the automated red lesion detection system. A comparison of visual and automated single-lesion detection in replicating the overall visual grading was then performed. RESULTS: Automated red lesion detection demonstrated a specificity of 71.4% and a resulting sensitivity of 96.7% in detecting diabetic retinopathy when applied at a tentative threshold setting for use in diabetic retinopathy screening. The accuracy of 79% could be raised to 85% by adjustment of a single user-supplied parameter determining the balance between the screening priorities, for which a considerable range of options was demonstrated by the receiver-operating characteristic (area under the curve 90.3%). The agreement of automated lesion detection with overall visual grading (0.659) was comparable to the mean agreement of six ophthalmologists (0.648). CONCLUSIONS: Detection of diabetic retinopathy by automated detection of single fundus lesions can be achieved with a performance comparable to that of experienced ophthalmologists. The results warrant further investigation of automated fundus image analysis as a tool for diabetic retinopathy screening.

Algorithms↗
PubMed2003

Evaluation of heredity as a determinant of retinal nerve fiber layer thickness as measured by optical coherence tomography.

PURPOSE: To study to what extent genetic factors determine the retinal nerve fiber layer thickness (RNFLT) in healthy subjects. METHODS: In vivo peripapillary optical coherence tomography (OCT), clinical examination, lens fluorescence, and fundus photography were performed on both eyes of 25 monozygotic and 25 dizygotic same-sex pairs of twins. The cross-sectional study included twins aged from 20 to 45 years recruited from a population-based register. Only healthy eyes were included. MAIN OUTCOME VARIABLES: peripapillary OCT RNFLT, reproducibility, and heritability (the proportion of the total observed variance statistically attributable to genetic factors). RESULTS: The within-pair difference in RNFLT was 4.6% (0.7%-15.2%; median [range]) in monozygotic versus 7.3% (0.2%-20%) in dizygotic twins (P = 0.032, Mann-Whitney test). The RNFLT heritability was 66%. The RNFLT measurement was found to decrease 3.8 microm per decade (P = 0.003). The RNFLT heritability increased to 82%, when corrected for the effect of age and excluding within-pair refractive differences of 2 D or more. The signal-to-noise ratio correlated with lens transmittance (r = 0.25, P = 0.012), age (r = -0.29, P = 0.004), and RNFLT (r = 0.43, P < 0.001). Intravisit RNFLT reproducibility was 4.2%. CONCLUSIONS: Peripapillary RNFLT in healthy adults, as measured by OCT, was determined predominantly by genetic factors in this study population. Theoretically, these factors may involve variations in the number of ganglion cells and nerve fiber formations early in life and/or in the rate at which these structures are subsequently lost.

Adult↗
PubMed2002

Retinal atrophy in idiopathic central serous chorioretinopathy.

PURPOSE: To study retinal atrophy in idiopathic central serous chorioretinopathy (ICSC). DESIGN: Observational case series. METHODS: Twenty-four eyes in 23 consecutive patients aged 33 to 67 years and 50 eyes in 25 healthy volunteers aged 24 to 70 years were studied. Observational procedures included: biomicroscopy, fundus photography, fluorescein angiography, optical coherence tomography, photocoagulation. Retinal thickness after resolution of detachment, definite attenuation being defined as foveal thickness less than the mean -2 SD in healthy volunteers; duration of symptoms; best-corrected visual acuity (BCVA). RESULTS: Definite retinal attenuation, retinal thickness ranging from 51% to 74% of normal, was found in nine eyes of nine patients with idiopathic central serous chorioretinopathy (ICSC). Their duration of symptoms was longer (P =.0014) and their BCVA was lower (P =.015) than eyes in patients with normal-range foveal thickness who, nevertheless, had thinner foveae than healthy subjects (P =.10). The most severe reduction of foveal thickness, to half the normal (three eyes of three patients), was associated with BCVA 0.5 or less, multifocal retinal pigment epithelial abnormalities, and more than 10 years' duration of symptoms. Retinal attenuation was seen only after a duration of symptoms of more than 4 months, being most pronounced in the photoreceptor layer, particularly in the fovea. CONCLUSION: Foveal attenuation in ICSC is associated with more than 4 months' duration of symptoms and persistent BCVA reduction despite resolution of the serous detachment. We found no other likely cause of atrophy than the prolonged absence of contact between photoreceptors and retinal pigment epithelial cells.

Adult↗
PubMed2002

Molecular analysis of KTI12/TOT4, a Saccharomyces cerevisiae gene required for Kluyveromyces lactis zymocin action.

TOT, the putative Kluyveromyces lactis zymocin target complex from Saccharomyces cerevisiae, is encoded by TOT1-7, six loci of which are isoallelic to RNA polymerase II (RNAPII) Elongator genes (ELP1-6). Unlike TOT1-3 (ELP1-3) and TOT5-7 (ELP5, ELP6 and ELP4 respectively), which display zymocin resistance when deleted, TOT4 (KTI12) also renders cells refractory to zymocin when maintained in multicopy or overexpressed from the GAL10 promoter. Elevated TOT4 copy number results in an intermediate tot phenotype, which includes mild sensitivities towards caffeine, Calcofluor white and elevated growth temperature, suggesting that TOT4 influences TOT/Elongator function. Tot4p interacts with Elongator, as shown by co-immunoprecipitation, and cell fractionation studies demonstrate partial co-migration with RNAPII and Elongator. As Elongator subunit interaction is not affected by either deletion of TOT4 or multicopy TOT4, Tot4p may not be a structural Elongator subunit but, rather, may regulate TOT/Elongator in a fashion that requires transient physical contact with TOT/Elongator. Consistent with a regulatory role, the presence of a potential P-loop motif conserved between yeast and human TOT4 homologues suggests capability of ATP or GTP binding and P-loop deletion renders Tot4p biologically inactive.

Adaptor Proteins, Signal Transducing↗