Chronic fatigue syndrome: Abnormally fast muscle fiber conduction in the membranes of motor units at low static force load.

OBJECTIVE: Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are disorders of unknown etiology and unclear pathophysiology, with overlapping symptoms of - especially muscular -fatigue and pain. Studies have shown increased muscle fiber conduction velocity (CV) in the non-painful muscles of FM patients. We investigated whether CFS patients also show CV abnormalities. METHODS: Females with CFS (n = 25), with FM (n = 22), and healthy controls (n = 21) underwent surface electromyography of the biceps brachii, loaded up to 20% of maximum strength, during short static contractions. The mean CV and motor unit potential (MUP) velocities with their statistical distribution were measured. RESULTS: The CV changes with force differed between CFS-group and both FM-group and controls (P = 0.01). The CV of the CFS-group increased excessively with force (P < 0.001), whereas that of the controls increased only slightly and non-significantly, and that of the FM-group did not increase at all. In the CFS-group, the number of MUPs conveying very high conduction velocities increased abundantly with force and the MUPs narrowed. CONCLUSION: Our results suggest disturbed muscle membrane function in CFS patients, in their motor units involved in low force generation. Central neural deregulation may contribute to this disturbance. SIGNIFICANCE: These findings help to detangle the underlying mechanisms of CFS.

The efficacy and safety of valganciclovir vs. oral ganciclovir in the prevention of symptomatic CMV infection in children after solid organ transplantation.

Routine prophylaxis for CMV with valganciclovir is common in adult recipients but data to support its use in children are scarce. The aim of this study was to compare the efficacy and safety of valganciclovir vs. ganciclovir in a pediatric cohort. We performed a retrospective analysis of 92 children after KTx and/or LTx. All children have received IV ganciclovir for two wk, and then oral ganciclovir (TID; n = 41) before 2004, or valganciclovir (OD; n = 51) thereafter. Treatment was given for three months in R+/D+ or R+/D- recipients and for six months in R-/D+. Patients were followed for one yr post transplant. Both groups were comparable in their demographic and transplant-related history. Symptomatic CMV infection/disease developed in 13.7% vs. 19.5% of valganciclovir and ganciclovir groups, respectively (P-NS). Time-to-onset of CMV infection was comparable in both groups (P-NS); rates of acute allograft rejection were similar in both groups (3.9% vs. 9.8%). Risk factors for CMV infection included young age, serostatus of R-/D+, and allograft from cadaver donor. No significant side effects were noted in both groups. As in adults, valganciclovir appears to be as efficacious and safe as oral ganciclovir. Valganciclovir should be considered as a possible prophylactic treatment for CMV in pediatric recipients of KTx or LTx.

Effects of the flaxseed lignans secoisolariciresinol diglucoside and its aglycone on serum and hepatic lipids in hyperlipidaemic rats.

The present study involved a comparative analysis of the effects of purified flaxseed lignans, secoisolariciresinol diglucoside (SDG) and its aglycone metabolite (SECO), in hyperlipidaemic rats. For hypercholesterolaemia, female Wistars (six rats per group) were fed a standard or 1 % cholesterol diet and orally administered 0, 3 or 6 mg SDG/kg or 0, 1.6 or 3.2 mg SECO/kg body weight once daily for 4 weeks. Hypertriacylglycerolaemia was induced in male Sprague-Dawley rats (ten rats per group) by supplementing tap water with 10 % fructose. These rats were orally administered 0, 3 or 6 mg SDG/kg body weight once daily for 2 weeks. Fasting blood samples (12 h) were collected predose and at the end of the dosing period for serum lipid analyses. Rats were killed and livers rapidly excised and sectioned for lipid, mRNA and histological analyses. Chronic administration of equimolar amounts of SDG and SECO caused similar dose-dependent reductions in rate of body-weight gain and in serum total and LDL-cholesterol levels and hepatic lipid accumulation. SDG and SECO failed to alter hepatic gene expression of commonly reported regulatory targets of lipid homeostasis. SDG had no effect on serum TAG, NEFA, phospholipids and rate of weight gain in 10 % fructose-supplemented rats. In conclusion, our data suggest that the lignan component of flaxseed contributes to the hypocholesterolaemic effects of flaxseed consumption observed in humans. Future studies plan to identify the biochemical mechanism(s) through which flaxseed lignans exert their beneficial effects and the lignan form(s) responsible.

Fibromyalgia: Increased reactivity of the muscle membrane and a role of central regulation.

OBJECTIVE: Fibromyalgia (FM) is characterized by widespread muscle pain and central neural deregulation. Previous studies showed increased muscle fiber conduction velocity (CV) in non-painful muscles of FM patients. This study investigates the relationship between central activation and the CV in FM. METHODS: Twenty-two females with primary FM and 21 controls underwent surface electromyography of the non-painful biceps brachii. Mean CVs were calculated from the motor unit potential velocities (CV-MUPs), and the CV-MUPs' statistical distributions were presented as histograms. The amount of muscle activity (average rectified voltage, ARV) was measured. RESULTS: The CV was higher in the FM-group than in the controls (P = 0.021), with CV-MUPs generally shifted to higher values, indicative of increased muscle membrane propagation speeds. The largest increase in the CV of the FM-group occurred when adopting and maintaining a limb position at only 5% of maximum strength (P < 0.001); the CV did not, as normal, increase with greater force. However, the ARV in both groups similarly increased with force. CONCLUSIONS: In fibromyalgia patients, the muscle membrane propagation speed increases independently of the force load or amount of muscle activity produced. When adopting a limb position, the patients show an augmented muscle membrane reaction, suggesting deregulation from higher neural centers. SIGNIFICANCE: These findings contribute to understanding fibromyalgia.

Risk of Skin Diseases in Maintenance Hemodialysis.

INTRODUCTION: Maintenance hemodialysis (HD) patients are potential transplant recipients. One of the most common cancers in the population of kidney recipients is skin neoplasm. Skin infections are also of a particular importance. In this population, especially in patients on the transplant waiting list, full dermatological examination, including dermatoscopy, should be carried out routinely. MATERIALS AND METHODS: The research was comprised of 105 HD patients (57 men, 48 women) with a mean age of 60.8 (range 25-94) years. The patients' skin condition was assessed and a dermatoscopic examination was performed. We compared the incidence of skin diseases in the two subpopulations: HD patients (n = 89) and HD patients active on the transplant waiting list (n = 16). RESULTS: Bacterial, fungal, and viral infections in the group of HD patients occurred in 24.7%, 14.6%, and 6.7% of patients, respectively. In HD patients on the waiting list, bacterial skin diseases were reported in 12.5% of patients, and neither fungal nor viral infections were noticed. Malignant skin lesions and precancerous conditions, such as basal cell carcinoma and keratosis actinic, developed in 4.5% and 3.4% of the HD patients. These malignancies did not occur in HD patients on the waiting list. The results show proper qualification for transplantation in maintenance HD patients before the waiting list. In the group of dialysis patients, 67.4% required dermatological care, while in the HD waiting group only 12.5% required dermatological care. CONCLUSIONS: The presented results prove the necessity of performing dermatological examinations on HD patients. Some dermatological skin lesions, if not diagnosed and treated, could progress to cancer after organ transplantation.

Level of Education and Knowledge of Skin Cancer Risk Factors in Patients Undergoing Maintenance Hemodialysis.

INTRODUCTION: An increased risk of skin cancer is particularly important in patients undergoing maintenance hemodialysis (HD), who are potential transplant recipients. In transplant recipients who are exposed to immunosuppressive therapy, neoplastic skin disease my take a more aggressive course. Increased exposure to photoradiation, elderly age, a low skin phototype, sunburn during childhood, and a history of smoking are the main factors contributing to the development of skin neoplasms. Knowledge of these risk factors as well as education on sun protection should be important for such patients. PATIENTS AND METHODS: We studied 105 HD patients (57 men, 48 women) with a mean age of 60.8 (range 25-94) years. Knowledge of skin cancer risk factors was assessed on the basis of a questionnaire regarding skin cancer risk factors. RESULTS: In the study group, 23.8% of patients claimed that they frequently and intensively engage in sunlight exposure. However, only 11.4% have started to apply sunblockers recently. Sunburn during adolescence was reported by 12.4% patients. Among the patients studied, 65.7% had skin phototype I or II, and only 34.3% had phototype III. In the investigated study group, 55.2% admitted smoking: 30.5% smoked more than 20 pack-years. Among the patients studied only 2.86% could name 3 skin cancer risk factors, 29.5% 2 risk factors, 60% 1 risk factor, and 7.6% could not name any risk factor. CONCLUSIONS: The results presented prove that patients undergoing HD lack knowledge regarding skin cancer risk factors, which explains the necessity of education, particularly on the dangers of sun radiation.

Paired Analysis of Outcomes After Kidney Transplantation in Peritoneal and Hemodialysis Patients.

BACKGROUND: The impact of dialysis modality before kidney transplantation (hemodialysis or peritoneal dialysis) on outcomes is not clear. In this study we retrospectively analyzed the impact of dialysis modality on posttransplant follow-up. METHODS: To minimize donor bias, a paired kidney analysis was applied. One hundred thirty-three pairs of peritoneal dialysis (PD) and hemodialysis (HD) patients were transplanted at our center between 1994 and 2016. Those who received kidneys from the same donor were included in the study. HD patients were significantly older (44 vs 48 years), but the Charlson Comorbidity Index was similar (3.12 vs 3.46) in both groups. The groups did not differ significantly with respect to immunosuppressive protocols and number of mismatches (2.96 vs 2.95). RESULTS: One-year patient (98% vs 96%) and graft (90% vs 93%) survival was similar in the PD and HD patient groups. The Kaplan-Meier curves of the patients and graft survival did not differ significantly. Delayed graft function (DGF) and acute rejection (AR) occurred significantly more often in the HD recipients. Graft vessel thrombosis resulting in graft loss occurred in 9 PD (6.7%) and 4 HD (3%) patients (P > .05). Serum creatinine concentration and estimated glomerular filtration rate (using the Modification of Diet in Renal Disease guidelines) showed no difference at 1 month, 1 year, and at final visit. On multivariate analysis, factors significantly associated with graft loss were graft vessel thrombosis, DGF, and graft function 1 month after transplantation. On univariate analysis, age, coronary heart disease, and graft loss were associated with death. Among these factors, only coronary heart disease (model 1) and graft loss were significant predictors of death on multivariate analysis. CONCLUSION: The long-term outcome for renal transplantation is similar in patients with PD and HD. These groups differ in some aspects, however, such as susceptibility to vascular thrombosis in PD patients, and to DGF and AR in HD patients.

Altered expression of SOCS3 in the hypothalamic arcuate nucleus during seasonal body mass changes in the field vole, Microtus agrestis.

We have previously shown that cold-acclimated (8 degrees C) male field voles (Microtus agrestis) transferred from short day (SD, 8 h light) to long day (LD, 16 h light) photoperiod exhibit an increase in body mass lasting 4 weeks, after which they stabilise at a new plateau approximately 7.5 g (24.8%) higher than animals maintained in SD. By infusing voles with exogenous leptin, we have also demonstrated that SD voles respond to the hormone by reducing body mass and food intake, whereas LD animals increasing body mass are resistant to leptin treatment. In the present study, we investigated whether seasonal changes in body mass could be linked to modulation of the leptin signal by suppressor of cytokine signalling-3 (SOCS3). We used in situ hybridisation to examine hypothalamic arcuate nucleus (ARC) expression of SOCS3, neuropeptide Y (NPY), agouti-related peptide (AgRP), pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) genes in 90 voles exposed to either SD or LD for up to 11 weeks. LD voles increasing body mass had significantly higher levels of SOCS3 mRNA than SD or LD voles with a stable body mass. There were no associated changes in expression of NPY, AgRP, POMC and CART genes. These results suggest that voles that regulate body mass at either the lower (SD) or upper (LD) plateau remain sensitive to leptin action, whereas SOCS3-mediated leptin resistance is a short-term mechanism that enables animals to move between the stable body mass plateaus. Our data provide evidence that expression of SOCS3 in the ARC is involved in the modulation of the strength of the leptin signal to facilitate seasonal cycles in body mass and adiposity.

One-year observation of kidney allograft recipients converted from cyclosporine microemulsion to tacrolimus.

The results from previous trials suggested that tacrolimus-based treatment in kidney transplantation was associated with a significantly lower incidence of acute rejection, and that cyclosporine microemulsion (CsA-Me)-treated patients converted to tacrolimus had numerically better 6-year graft survival than those remaining on CsA-Me. Death with a functioning graft and chronic graft nephropathy are the leading causes of late allograft loss. While standard cardiovascular risk factors are relevant, renal function itself becomes an important risk factor for cardiovascular morbidity and mortality in kidney transplantation patients. Expected benefits of the conversion from CsA-Me to tacrolimus with respect to renal function and cardiovascular status were the rationale for this observational study. Twenty one patients underwent conversion due to nephrotoxicity of cyclosporine (n = 18) or side effects (n = 3). Two out of 21 patients did not complete the study. The patient survival after 1 year was 100% in this group of patients; graft survival 94.7%. No cases of de novo diabetes mellitus were identified. Mean serum creatinine fell from 2.13 +/- 0.4 to 1.84 +/- 0.3 mg/dL (P < .02) and calculated glomerular filtration rate increased from 49.6 +/- 14.4 to 56.2 +/- 15.5 mL/min (P < .01). Total cholesterol decreased from 229.4 +/- 50.1 to 195.9 +/- 28.5 mg/dL (P < .005) and, low-density lipoprotein cholesterol from 125.7 +/- 37.3 to 104.4 +/- 22.6 mg/dL (P < .02). No significant changes in mean systolic or diastolic pressure or blood glucose levels were observed. The results of this observational study showed that in a group of patients with raised creatinine levels at entry, conversion to tacrolimus resulted in improved graft function and a more favorable cardiovascular risk profile.

Do Patients With End-Stage Chronic Renal Failure Treated With the Use of Hemodialysis Have Healthy Skin? Evaluation of Skin Lesions and Basic Education About Risk Factors for Skin Cancer in This Patient Population.

BACKGROUND: Considering the increasing incidence of skin cancers in patients after renal transplantation, evaluation of skin condition in dialysis patients, from whom kidney transplant recipients are recruited, appears to be very important. Particular importance is attached to the identification of such dialysis patients in the population who require dermatologic care before qualifying for transplantation. The objective of this study was to determine the prevalence of skin diseases in the dialysis patient population. Education of the patients regarding risk factors for skin cancer and the need for sun protection was performed. METHODS: Full dermatologic examination, including dermatoscopy, was performed on a group of 77 dialysis patients (38 women, 39 men) and a control group of 77 healthy people (60 women, 17 men). RESULTS: Eight hemodialysis patients had healthy skin compared with 33 people from the control group. In the remaining hemodialysis patients, the following skin lesions were observed: 1) inflammatory and allergic skin disorders in 17 patients; 2) bacterial, fungal, and viral infections in 26 patients; 3) benign lesions in 39 patients; 4) malignant skin lesions and precancerous conditions in 4 patients; and 5) other skin changes in 63 patients. CONCLUSIONS: Skin lesions are common in the dialysis patient population. Only 10% of the examined population had completely healthy skin, compared with 43% of the control group. More than one-half of dialysis patients required dermatologic care compared with one-third of healthy control subjects.

Venus Flytrap HKT1-Type Channel Provides for Prey Sodium Uptake into Carnivorous Plant Without Conflicting with Electrical Excitability.

The animal diet of the carnivorous Venus flytrap, Dionaea muscipula, contains a sodium load that enters the capture organ via an HKT1-type sodium channel, expressed in special epithelia cells on the inner trap lobe surface. DmHKT1 expression and sodium uptake activity is induced upon prey contact. Here, we analyzed the HKT1 properties required for prey sodium osmolyte management of carnivorous Dionaea. Analyses were based on homology modeling, generation of model-derived point mutants, and their functional testing in Xenopus oocytes. We showed that the wild-type HKT1 and its Na(+)- and K(+)-permeable mutants function as ion channels rather than K(+) transporters driven by proton or sodium gradients. These structural and biophysical features of a high-capacity, Na(+)-selective ion channel enable Dionaea glands to manage prey-derived sodium loads without confounding the action potential-based information management of the flytrap.

Gastrointestinal Pathologies in Patients After Successful Renal Transplantation-A Pilot Study.

BACKGROUND: The beneficial effect of kidney transplantation in patients requiring continuous renal replacement therapy owing to chronic kidney disease is well known and accepted. Kidney transplantation protects the patient from complications that may develop during chronic dialysis. Unfortunately, there is also evidence that kidney transplant patients are more prone to developing cancer than healthy persons. The aim of this study was to evaluate the prevalence of gastrointestinal pathologies in patients after kidney transplantation. METHODS: Adult patients after kidney transplantation, who are under the care of the Outpatient Department of Nephrology in Gdansk, received alarm symptom questionnaires and referral for testing for the presence of fecal occult blood. Then, in 45 selected patients (29 men and 16 women) endoscopic examination was performed. Mean age was 57.6 ± 10.1 (range, 35-83) years. RESULTS: Out of ∼940 patients after kidney transplantation, resting under supervision of outpatient department, 181 patients completed the questionnaire and 100 gave a stool sample for testing: 32 results were positive. After analyzing the questionnaires and stool results, 88 patients were qualified for further investigation. The endoscopic examination had been performed so far in 45 patients and revealed gastritis and/or duodenitis in 33 patients, diverticular colon disease in 18, esophagitis in 8, colon polyps in 14, stomach polyps in 3, inflammatory bowel disease in 7, and cancers in 3. CONCLUSIONS: The preliminary results indicate that patients after kidney transplantation have significant risk of gastrointestinal pathologies and require detailed diagnostic endoscopy.

Expression pattern of Rhizobium etli ccmIEFH genes involved in c-type cytochrome maturation.

In different bacterial species, ccmIEFH genes have been suggested to code for subunits of a bacterial haem-lyase catalyzing the covalent attachment of haem to c-type apoproteins. In Rhizobium etli CE3 there are two copies of ccmIEFH: one in the chromosome and the other located in plasmid pf. However, the null phenotype of chromosomal ccmF mutant indicates that the gene locus of plasmid pf is not functional. Two ccmI chromosomal mutants, previously isolated, produced detectable levels of c-type cytochromes under certain culture conditions in contrast with the ccmF mutant, suggesting that ccmF could be transcribed independently. The transcriptional organization of ccmIEFH operon was established. Two promoters from the chromosomal locus were mapped by primer extension, one located upstream of ccmI and the second located upstream of ccmF. The regulation of the expression of both promoters was studied using appropriate lacZ gene fusions (ccmI-lacZ and ccmEF-lacZ). The ccmI-lacZ gene fusion was expressed in complex medium, during exponential growth, under microaerobic conditions and in a R. etli mutant that accumulates reducing power, conditions where a higher respiration rate could be limited by c-type cytochrome content. The ccmEF-lacZ fusion was also primarily expressed in complex medium and under microaerophilic conditions. The finding of two independent promoters in this gene locus could suggest that the step catalyzed by CcmFH could be a rate-limiting step for c-type cytochrome assembly under certain culture conditions.

Oxidation of 4-alkylphenols and catechols by tyrosinase: ortho-substituents alter the mechanism of quinoid formation.

Numerous phenols and catechols are known to be substrates for tyrosinase. While the catalytic mechanism of phenol oxidation by tyrosinase has been well studied, little work has been done to determine the influence of substituents on the reaction. In the present investigation, we explored the effects of changing substituents at the 2 and 6 position on the mechanism of tyrosinase-catalyzed oxidation of 4-allyl and 4-propylphenols and catechols. We have previously demonstrated that tyrosinase initially oxidizes hydroxychavicol (4-allyl-catechol) to an o-quinone (3,5-cyclohexadien-1,2-dione) which because of the relatively acidic protons in the benzyl position, readily isomerizes to the tautomeric p-quinone methide (4-allylidene-2,5-cyclohexadien-1-one, QM) (Bolton et al., 1994). We have confirmed through GSH trapping studies that oxidation of 4-allylphenol by tyrosinase yields the same o-quinone GSH conjugates as hydroxychavicol. In contrast, the presence of additional ortho substituents dramatically alters the mechanism of tyrosinase-catalyzed oxidation of 4-alkylphenols. For example, eugenol (4-allyl-2-methoxyphenol), which possesses 1 ortho-methoxy substituents, is not oxidized to a o-quinone or a QM. However, when both ortho o-quinones or QMs which may be selectively toxic to the malignant melanocyte. Although mammalian tyrosinase is much more substrate specific compared to the mushroom tyrosinase used in this study [42], it should be possible to identify compounds which are substrates for the mammalian form but are otherwise oxidatively stable. In order to develop such target compounds an improved understanding of substituent effects on tyrosinase-catalyzed oxidation of catechols and phenols is necessary. This should for the development of strategies for therapeutic compounds that are selectively toxic toward melanoma.

The reactivity of o-quinones which do not isomerize to quinone methides correlates with alkylcatechol-induced toxicity in human melanoma cells.

Catechols are widespread in the environment, especially as constituents of edible plants. A number of these catechols may undergo oxidative metabolism to electrophilic o-quinones (3,5-cyclohexadien-1,2-dione) by oxidative enzymes such as cytochrome P450 and peroxidases. Alkylation of cellular nucleophiles by these intermediates and the formation of reactive oxygen species, especially through redox cycling of o-quinones, could contribute to the cytotoxic properties of the parent catechols. In contrast, isomerization of the o-quinones to electrophilic quinone methides (4-methylene-2,5-cyclohexadien-1-one, QM) could cause cellular damage primarily through alkylation. In this investigation, we treated human melanoma cells with two groups of catechols. These cells have high levels of tyrosinase required to oxidize catechols to quinoids. For catechols which are oxidized to o-quinones that cannot isomerize to quinone methides or form unstable quinone methides, plots of the cytotoxicity data (ED50) versus the reactivity of the o-quinones gave an excellent linear correlation; decreasing o-quinone reactivity led to a decrease in the cytotoxic potency of the catechol. In contrast, catechols which are metabolized by the o-quinone/p-quinone methide bioactivation pathway were equally cytotoxic but showed no correlation between the reactivity of the o-quinones and the cytotoxic potency of the catechols. The most likely explanation for this effect is a change in cytotoxic mechanism from o-quinone-mediated inhibition of cell growth to a bioactivation pathway based on both o-quinone and p-QM formation. These results substantiate the conclusion that the involvement of the o-quinone/ QM pathway in catechol toxicity depends on a combination between the rate of enzymatic formation of the o-quinone, the rate of isomerization to the more electrophilic QM, and the chemical reactivity of the quinoids.

Mechanisms of dimer and trimer formation from ultraviolet-irradiated alpha-tocopherol.

Alpha-Tocopherol (alpha-TH) undergoes ultraviolet (UV)-induced photooxidation on the surface of mouse skin to produce a dihydroxydimer, a spirodimer, and trimers as the major products. To study the photochemistry involved, we UV-irradiated alpha-TH in a thin film on a glass petri dish. Photooxidation yielded a mixture of dihydroxydimer, spirodimer, and trimers. In the time-course studies, the dihydroxydimer accumulated and then was further oxidized, whereas the spirodimer and trimers accumulated more gradually. Reaction of two tocopheroxyl radicals forms the dihydroxydimer, whereas the spirodimer may be formed either by photooxidation of alpha-TH to an orthoquinone methide (o-QM) followed by a Diels-Alder reaction or by photooxidation of alpha-TH to the dihydroxydimer, followed by two-electron oxidation. Irradiation of a mixture of d10-labeled and unlabeled (d0) dihydroxydimer produced a mixture of labeled and unlabeled spirodimers as detected by positive atmospheric pressure chemical ionization-mass spectrometry. The absence of mixed label spirodimers among products indicated that direct oxidation of the dihydroxydimer is a facile route to the spirodimer and is probably the major spirodimer-forming reaction in alpha-TH photooxidations. Trimer formation from the dihydroxydimer and the spirodimer was observed, however, and requires an o-QM intermediate. Photooxidation of dl0-labeled and unlabeled (d0) dihydroxydimers yielded mixed isotopomers of the trimer products, thus demonstrating that the dihydroxydimer and spirodimers underwent conversion to o-QM intermediates. Photochemical conversion of alpha-TH to UV-absorbing dimer and trimer products may contribute to photoprotection by topically applied alpha-TH.

Topologic preconditions for ring chromatids.

The paper discusses a mechanism apt to convert the topology of a straight chromatid into one that could lead to the formation of a O-ring. It is predicted that such conversions might occur only in exceptional circumstances, due to a combination of poorly correlated events.

Hemolytic anemia after renal transplantation: analysis of case reports.

Hemolysis after renal transplantation in some cases is clearly related to hemolytic-uremic syndrome (HUS) and usually attributed to cyclosporine (CsA) treatment. Acute hemolysis in other recipients is related to anti-erythrocyte autoantibodies. In most cases these patients have received ABO-compatible, although ABO-nonidentical, organs, mostly from O blood group donors. We report three cases of autoimmune hemolytic anemia after renal transplantation. Two patients (patients: 1 and 2; ABO-compatible, but nonidentical kidneys) suffered acute hemolysis in the third week after transplantation. One patient (patient 3: ABO-identical kidney) suffered a chronic, subclinical course of disease beginning 5 months after transplantation. The clinical picture of this disease was completely different from HUS. The existence of severe anemia (patients 1 and 2), hyperbilirubinemia (particularly high in patient 3), increased serum lactic dehydrogenase levels, and decreased serum haptoglobin in the presence of good graft function suggested an hemolytic anemia. In all patients the direct antiglobulin test was positive. The acute or chronic symptoms of hemolysis disappeared, at 2 and 5 weeks, respectively, after conversion from CsA to tacrolimus. Hemolysis in these patients probably relates to alloantibodies derived from passenger B lymphocytes transplanted with the organs. Because hemolysis has been most frequently related to CsA therapy, it is suggested that B lymphocytes proliferated and produced antibodies because CsA effects to inhibit T-cell function generally spares B-cell activity. It is proposed that a subtype of B cells, which are resistant to CsA, produces anti-A and/or anti-B antibodies. Treatment with tacrolimus appears to be successful, probably due to its alternate, and likely more effective, manner of B-cell suppression.

A study of the connectedness among distant neuronal populations in the human brain during mental activity.

In this article, we present the results of a study of connectedness among distant neuronal populations in human deep-brain structures. The time characteristics involved and the stability of the connections between different neuronal populations during monotonous mental activity are discussed. We show that a stable connectedness does correlate with mental activity; however, the connections themselves do not correlate with one another. We also show that the individual connections, the elements of the system which make mental activity possible, can function with various degrees of rigidity or flexibility.

[Stable maintenance of dicentric mini-chromosomes in CHL4 mutants in yeast]. / Stabil'noe podderzhanie ditsentricheskikh mini-khromosom u mutanta drozhzhei po genu chl4.

Earlier we have identified the chl4-1 mutation in a screen for yeast mutants with increased loss of chromosome III and circular artificial minichromosome in mitosis. Mutation in the CHL4 gene leads to a 50-100-fold promotion in the rate of chromosome loss per cell division compared to the isogenic wild type strain. Detailed analysis of behaviour of the circular minichromosome marked by the CUP1 gene has shown that minichromosome nondisjunction (2:0 segregation) leading to an increase in the copy number of minichromosome in part of a cell population is the main reason of minichromosome instability in the mutant. The unique peculiarity of chl4-1 mutation is the ability of the strains carrying this mutation to stably maintain circular dicentric minichromosomes without any rearrangement during many generations. (In the wild type strains dicentric minichromosomes are extremely unstable. As a consequence of that there is a strong selection for cells harboring monocentric derivatives in a population of cells derived from a cell containing a dicentric plasmid). Introduction of the second centromere into one of the natural chromosomes (chromosomes II or III) in the chl4-1 mutant leads to the same dramatic consequences as that in the wild type strain (mitotic lag of cells harboring dicentric chromosomes and, as a result of that, selective pressure for cells harboring monocentric derivatives of dicentric chromosome). A genomic clone of CHL4 was isolated by complementation of the chl4-1 mutation. Nucleotide sequence analysis of CHL4 revealed a 1.4-kb open reading frame with a predicted 53-kDa protein sequence. Analyzing the sequence of the CHL4 protein we have found a region meeting the necessary requirements for the helix-turn-helix (HTH) structure. This region of the CHL4 protein has about 40% homology with the repressor of tryptophane operon (TrpR) of E. coli. A strain containing a null allele of CHL4 was viable under standard growth conditions, but had temperature-sensitive phenotype (conditional lethality at 34 degrees C). We suggest that the CHL4 gene product is one of the components of the segregation cell machinery.