Relationship between iron deficiency and expression of genes involved in iron metabolism in human myocardium and skeletal muscle.

BACKGROUND: Iron deficiency (ID) is associated with adverse prognosis in patients with heart failure. This study aims to investigate the relationship between ID and expression of genes involved in iron metabolism in human myocardium and skeletal muscle, focusing on Transferrin 1 receptor (TfR1), the main pathway of cellular iron uptake. METHODS: Patients undergoing elective CABG were assessed prior to surgery with echocardiography and serum iron parameters. Core needle biopsies were collected from the left and right ventricle (LV, RV), the right atrium and intercostal skeletal muscle (SM). Gene expression analyses were done by mRNA sequencing. RESULTS: Of 69 patients (median age 69 years, 91% men), 28% had ID. 26% had HFrEF, 25% had HFpEF physiology according to echocardiographic findings and NT-proBNP levels, and 49% had normal LV function. The expression of TfR1 was increased in patients with ID compared to patients without ID in ventricular tissue (p = 0.04) and in intercostal SM (p = 0.01). The increase in TfR1 expression in LV and RV was more pronounced when analysing patients with absolute ID (S-Ferritin<100 µg/L). Analysing the correlation between various iron parameters, S-Ferritin levels showed the strongest correlation with TfR1 expression. There was no correlation with NT-proBNP levels and no difference in TfR1 expression between different HF phenotypes. CONCLUSIONS: In patients undergoing elective CABG we found an association between ID and increased TfR1 expression in myocardium regardless of LV function, indicating physiologically upregulated TfR1 expression in the presence of ID to restore intracellular iron needs. CLINICAL TRIAL REGISTRATION: Clinicaltrials.govNCT03671122.

Associations between echocardiographic manifestations and bacterial species in patients with infective endocarditis: a cohort study.

BACKGROUND: The diagnosis of infective endocarditis (IE) is based on microbiological analyses and diagnostic imaging of cardiac manifestations. Echocardiography (ECHO) is preferred for visualization of IE-induced cardiac manifestations. We investigated associations between bacterial infections and IE manifestations diagnosed by ECHO. METHODS: In this cohort study, data from patients aged 18 years or above, with definite IE admitted at the Karolinska University Hospital between 2008 and 2017 were obtained from Swedish National Registry of Endocarditis. Bacteria registered as pathogen were primarily selected from positive blood culture and for patients with negative blood culture, bacteria found in culture or PCR from postoperative material was registered as pathogen. Patients with negative results from culture or PCR, and patients who did not undergo ECHO during hospital stay, were excluded. IE manifestations diagnosed by ECHO were obtained from the registry. Chi-squared test and two-sided Fisher's exact test was used for comparisons between categorical variables, and student's t test was used for continuous numerical variables. Multivariable analyses were performed using logistic regression. Secular trend analyses were performed using linear regression. Associations and the strength between the variables were estimated using odds ratios (ORs) with 95% confidence intervals (CIs). P < 0.05 was considered significant. RESULTS: The most common bacteria were Staphylococcus aureus (n = 239, 49%) and viridans group streptococci (n = 102, 21%). The most common manifestations were vegetation in the mitral (n = 195, 40%), aortic (n = 190, 39%), and tricuspid valves (n = 108, 22%). Associations were seen between aortic valve vegetations and Enterococcus faecalis among patients with native aortic valves, between mitral valve vegetations and streptococci of group B or viridans group, between tricuspid valve vegetations and S. aureus among patients with intravenous drug abuse, and between perivalvular abscesses as well as cardiovascular implantable electronic device (CIED)-associated IE and coagulase negative staphylococci (all P < 0.05). CONCLUSIONS: Associations were found between certain bacterial species and specific ECHO manifestations. Our study contributes to a better understanding of IE manifestations and their underlying bacterial etiology, which pathogens can cause severe infections and might require close follow-up and surgical treatment.

Ultrasound measurements of carotid intima-media thickness by two semi-automated analysis systems.

Increased carotid intima-media thickness (cIMT) is associated with an increased risk of cardiac events and stroke. Several semi-automated edge-detection techniques for measuring cIMT are used for research and in clinical practice. Our aim was to compare two currently available semi-automated techniques for the measurement of cIMT. Carotid ultrasound recordings were obtained from 99 subjects (mean age 54·4 ± 8·9 years, range 33-69) without known cardiovascular diseases using a General Electric (GE) Vivid 7 ultrasound scanner, 8-MHz transducer. The far-wall cIMT was evaluated 1-2 cm proximal to the carotid bulb. Three diastolic images (ECG R-wave) from the left and three images from the right common carotid arteries were analysed using GE and Artery Measurement System (AMS) semi-automated softwares. Mean systolic and diastolic blood pressures were 120 ± 13 and 76 ± 8 mmHg, respectively. The cIMTmean (left + right)/2 by GE and cIMTmean (left + right)/2 AMS were highly correlated (r = 0·92, P<0·001). Higher values were measured by GE (0·72 ± 0·12 mm) compared with AMS (0·69 ± 0·12 mm), and this was significant (P<0·001). The coefficients of variation for the intra-observer variability of cIMTmean (left + right)/2 were 1·0% (GE) and 2·2% (AMS). cIMTmean measured by GE's semi-automated edge-detection method correlated well with that measured by AMS. However, there were small but significant systematic differences between the cIMTmean values measured by the two techniques. Thus, the use of only one type of measurement program seems favourable in follow-up studies and when evaluating treatment effects.

Cardiac function in mild primary hyperparathyroidism and the outcome after parathyroidectomy.

OBJECTIVE: Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity. The extent of cardiovascular abnormalities in patients with mild-asymptomatic disease is unclear. Using sensitive echocardiographic methods, we compared cardiac structure and function in patients with mild PHPT and in healthy controls, and evaluated the changes after parathyroidectomy (PTX). METHODS: In a prospective case-control design, we studied 51 PHPT patients without any cardiovascular risk factors/diseases and 51 healthy matched controls. Cardiac structure, and systolic and diastolic function were evaluated by echocardiography and Doppler tissue imaging (DTI). Blood pressure (BP) and heart rate were measured. RESULTS: We observed no differences in systolic or diastolic function or in cardiac morphology between the PHPT patients and the age-matched healthy controls. The regional peak systolic myocardial velocities (S') measured with DTI decreased at all sites (P<0.05) after PTX (tricuspid annulus 14.23+/-1.85 to 13.48+/-1.79, septal 8.48+/-0.96 to 7.97+/-0.85, and lateral 9.61+/-2.05 to 8.87+/-1.63 cm/s, part of the mitral annulus). At baseline, systolic BP was higher in patients compared to controls (127.6+/-17.1 vs 119.6+/-12.6 mmHg, P<0.05). After PTX, both systolic (127.6+/-17.1 vs 124.6+/-16.6 mmHg, P<0.05) and diastolic (80.3+/-9.6 vs 78.4+/-8.6 mmHg, P<0.05) BP decreased. CONCLUSIONS: Our results indicate that patients with PHPT without cardiovascular risk factors have a normal global systolic and diastolic function and cardiac morphology. BP and the systolic velocities were marginally reduced after PTX, but reflected the values of the control group. Our findings warrant further investigation of the clinical and prognostic significance of these possibly disease-related inotropic effects.

Eleven years' experience with the Biocor stentless aortic bioprosthesis: clinical and hemodynamic follow-up with long-term relative survival rate.

OBJECTIVE: The long-term durability and hemodynamics of stentless valves are largely unknown. Our aim was to prospectively investigate long-term hemodynamic function and clinical outcome after aortic valve replacement with the Biocor stentless aortic bioprosthesis. PATIENTS AND METHODS: Between October 1990 and November 2000 we inserted the Biocor stentless aortic valve in 112 patients (male/female: 38:74) with a mean age of 78.5 years (median 79.3, range 60-88). The predominant diagnosis was aortic stenosis in 86% of the patients. Concomitant coronary artery bypass surgery was performed in 31% of the patients. Average prosthetic valve size was 23.3+/-1.6 mm. All patients were followed in a prospective study with a mean follow-up of 66+/-33 months. The follow-up was 100% complete with a closing interval from October 1 to December 31, 2001. The observed actuarial survival of patients was compared to expected survival for an age- and gender-matched comparison population as calculated from Swedish life tables by Statistics Sweden. Relative survival rates were calculated annually for the patient population. RESULTS: Early mortality was 7% (8/112). Late mortality was 38% (43/112). Actuarial survival at 5 and 9 years was 74+/-5% and 38+/-7%, respectively. Observed survival among patients was not different from the expected survival for the comparison population and calculation of relative survival rates indicates a 'normalized' survival pattern for the patient population. At 5 and 9 years the actuarial freedom from valve-related death was 94+/-3% and 86+/-6%; from cardiac death, 82+/-4% and 57+/-8%; from valve reoperation, 96+/-2% and 87+/-6%; from structural valve degeneration, 96+/-2% and 87+/-6%; from thromboembolism, 89+/-4% and 71+/-9%; and from endocarditis, 96+/-2% and 90+/-5%. At 9 years the transvalvular mean pressure difference for all valves was 7.3+/-1.3 mmHg (range 6-10 mmHg) measured with Doppler echocardiography. Aortic regurgitation progressed slowly over time in a few patients and necessitated reoperation in two patients. CONCLUSION: The Biocor stentless bioprosthesis has an excellent hemodynamic function and confers a good long-term outcome. This patient population could be regarded as 'cured' from valve disease since the observed survival did not differ from the expected survival for an age- and gender-matched Swedish comparison population, a conclusion that is also supported by a constant relative survival after the first postoperative year. However, despite excellent long-term hemodynamics, patients with stentless bioprostheses need to be evaluated with echocardiography at regular intervals to discover the rare cases of progressive aortic regurgitation.

Continuous haemodynamic monitoring during withdrawal of diuretics in patients with congestive heart failure.

AIMS: Right heart pressure parameters can be recorded continuously with the help of an implanted haemodynamic monitor. The aim of this study was to investigate the usefulness of the device in adjusting diuretic medication in patients with chronic congestive heart failure, and to evaluate the response of right ventricular pressure to increased volume load induced by diuretic withdrawal. METHODS AND RESULTS: Four patients with stable congestive heart failure were implanted with an implantable haemodynamic monitor. Furosemide, the only diuretic used, was reduced by 50% the first week, withdrawn completely for the second week and then reinstituted in the initial dose. Right ventricular systolic and diastolic pressure, pulse pressure, dP/dt, estimated diastolic pulmonary artery pressure and heart rate were sampled continuously. Patients were evaluated by body weight, NYHA class, serum creatinine, serum brain natriuretic peptide, the 6 min walk test, quality of life and echocardiography on days 0, 7, 14 and 21. We observed significant changes in right ventricular pressure parameters in parallel with clinical signs and symptoms of worsening heart failure, such as increased body weight, a shorter walking distance and impaired quality of life. Moreover elevated levels of brain natriuretic peptide and lower creatinine levels were observed. CONCLUSION: Haemodynamic changes due to increased volume load can be detected with an implantable haemodynamic monitor. Such data provide useful information for tailoring an optimal diuretic dose in patients with congestive heart failure.

Dilation of the sinotubular junction causes aortic insufficiency after aortic valve replacement with the Toronto SPV bioprosthesis.

OBJECTIVE: This study was undertaken to examine the causes of late aortic insufficiency in patients who had aortic valve replacement with the Toronto SPV bioprosthesis (St Jude Medical, Inc, St Paul, Minn). METHODS: From 1991 to 1996, 174 patients with a mean age of 63 +/- 11 years underwent aortic valve replacement with the Toronto SPV bioprosthesis and were evaluated annually by Doppler echocardiographic studies to assess valve function. The diameters of the aortic root were retrospectively measured in all patients who had aortic insufficiency and also in a random sample of 23 patients without aortic insufficiency. The mean follow-up was 5.8 years (range 4 to 9 years). RESULTS: Aortic insufficiency greater than 1+ developed in 19 patients. The diameter of the sinotubular junction increased in these patients and did not change in those without aortic insufficiency. The ratio between the diameter of the sinotubular junction and the size of the Toronto SPV bioprosthesis increased in patients who had aortic insufficiency and did not change in those without aortic insufficiency. Both 2-way analysis of covariance and analysis by a mixed linear model demonstrated a significant difference in slopes between the patients with aortic insufficiency greater than 1+ and in those without insufficiency for the ratio of the diameter of the sinotubular junction/diameter of the Toronto SPV relationships over time (aortic insufficiency. Year; P <.001). Structural valve deterioration was observed in 5 valves, and in 4 of them the sinotubular junction of the aortic root had dilated. The freedom from structural valve deterioration was 99% +/- 1% for patients without aortic insufficiency and 82% +/- 12% for those with aortic insufficiency of more than 1+ at 8 years (P =.004). One patient had moderate aortic insufficiency without structural valve deterioration and dilation of the sinotubular junction. CONCLUSIONS: Dilation of the sinotubular junction causes aortic insufficiency after aortic valve replacement with the Toronto SPV bioprosthesis and increases the risk of structural valve deterioration. Banding the sinotubular junction may prevent dilation and enhance the durability of this valve.

Novel form of ClpB/HSP100 protein in the cyanobacterium Synechococcus.

Synechococcus sp. strain PCC 7942 has a second clpB gene that encodes a 97-kDa protein with novel features. ClpBII is the first ClpB not induced by heat shock or other stresses; it is instead an essential, constitutive protein. ClpBII is unable to complement ClpBI function for acquired thermotolerance. No truncated ClpBII version is normally produced, unlike other bacterial forms, while ectopic synthesis of a putative truncated ClpBII dramatically decreased cell viability.

Mild-to-moderate hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentrations of asymmetric dimethylarginine.

OBJECTIVES: The aim of this study was to investigate endothelial function and common carotid intima-media thickness (IMT) in healthy young men with mild-to-moderate hypertriglyceridemia. Plasma asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, was measured to further elucidate the mechanisms involved. BACKGROUND: Hypertriglyceridemia is a risk factor for coronary heart disease although the mechanisms behind the increased risk remain to be defined. Acute elevation of plasma triglycerides induced by an intravenous fat load is associated with impaired endothelial function. The results of studies examining acute effects induced by a high-fat meal or effects of chronic hypertriglyceridemia on endothelial function are more inconsistent. METHODS: Flow-mediated vasodilation and nitroglycerin-induced vasodilation of the brachial artery and common carotid IMT were measured noninvasively by ultrasound technique in 15 hypertriglyceridemic (HTG) subjects and 15 matched controls, mean age 34 years. Plasma concentrations of ADMA were measured by high-performance liquid chromatography. RESULTS: Flow-mediated vasodilation was decreased in the HTG group (p < 0.0001), whereas nitroglycerin-induced vasodilation and carotid IMT did not differ significantly. Asymmetric dimethylarginine concentrations were higher in the HTG group (p < 0.05). CONCLUSIONS: Hypertriglyceridemia in young men is associated with endothelial dysfunction and increased plasma concentration of ADMA but not with increased IMT of the common carotid artery. The corollary is that chronic hypertriglyceridemia results in endothelial dysfunction, possibly due to increased ADMA concentration, and that endothelial dysfunction might precede increased IMT among the early manifestations of atherosclerosis.

Effects of C-peptide on forearm blood flow and brachial artery dilatation in patients with type 1 diabetes mellitus.

Recent studies suggest that C-peptide increases blood flow in both exercising and resting forearm in patients with type 1 diabetes. Now we have studied the effect of C-peptide administration on endothelial-mediated and non-endothelial-mediated arterial responses as well as central haemodynamics in 10 patients with type 1 diabetes in a placebo-controlled double-blind study. Euglycaemia was maintained with an i.v. insulin infusion before and during the study. A high-resolution ultrasound technique and Doppler echocardiography were used to assess haemodynamic functions. Brachial artery blood flow and brachial artery diameter were measured in the basal state, 1 and 10 min after reactive hyperaemia and 4 min after sublingual glyceryl trinitrate administration (GTN; endothelial-independent vasodilatation), both before and after the end of 60-min C-peptide (6 pmol kg-1 min-1) or saline infusion periods. Echocardiographic measurements were also performed before and at the end of the infusion periods. Seven healthy age-matched males served as controls for vascular studies. The patients showed a blunted brachial dilatation after reactive hyperaemia in comparison with the healthy controls (2.1 +/- 0.5% vs. 9.3 +/- 0.3%, P < 0.001), indicating a disturbed endothelial function. C-peptide infusion compared with saline resulted in increased basal blood flow (33 +/- 6%, P < 0.001) and brachial arterial dilatation (4 +/- 1%, P < 0.05). Left ventricular ejection fraction seemed to be improved (5 +/- 2%, P < 0.05) at the end of C-peptide infusion compared with placebo. The vascular response to reactive hyperaemia and GTN was not affected by C-peptide infusion. Our results demonstrate that physiological concentrations of C-peptide increase resting forearm blood flow, brachial artery diameter and left ventricular systolic function in patients with type 1 diabetes.

The truncated form of the bacterial heat shock protein ClpB/HSP100 contributes to development of thermotolerance in the cyanobacterium Synechococcus sp. strain PCC 7942.

ClpB is a highly conserved heat shock protein that is essential for thermotolerance in bacteria and eukaryotes. One distinctive feature of all bacterial clpB genes is the dual translation of a truncated 79-kDa form (ClpB-79) in addition to the full-length 93-kDa protein (ClpB-93). To investigate the currently unknown function of ClpB-79, we have examined the ability of the two different-sized ClpB homologues from the cyanobacterium Synechococcus sp. strain PCC 7942 to confer thermotolerance. We show that the ClpB-79 form has the same capacity as ClpB-93 to confer thermotolerance and that the ClpB-79 protein contributes ca. one-third of the total thermotolerance developed in wild-type Synechococcus, the first in vivo demonstration of a functional role for ClpB-79 in bacteria.

The Escherichia coli heat shock protein ClpB restores acquired thermotolerance to a cyanobacterial clpB deletion mutant.

In both prokaryotes and eukaryotes, the heat shock protein ClpB functions as a molecular chaperone and plays a key role in resisting high temperature stress. ClpB is important for the development of thermotolerance in yeast and cyanobacteria but apparently not in Escherichia coli. We undertook a complementation study to investigate whether the ClpB protein from E coli (EcClpB) differs functionally from its cyanobacterial counterpart in the unicellular cyanobacterium Synechococcus sp. PCC 7942. The EcClpB protein is 56% identical to its ClpB1 homologue in Synechococcus. A plasmid construct was prepared containing the entire E coli clpB gene under the control of the Synechococcus clpB1 promoter. This construct was transformed into a Synechococcus clpB1 deletion strain (deltaclpB1) and integrated into a phenotypically neutral site of the chromosome. The full-length EcClpB protein (EcClpB-93) was induced in the transformed Synechococcus strain during heat shock as well as the smaller protein (EcClpB-79) that arises from a second translational start inside the single clpB message. Using cell survival measurements we show that the EcClpB protein can complement the Synechococcus deltaclpB1 mutant and restore its ability to develop thermotolerance. We also demonstrate that both EcClpB-93 and -79 appear to contribute to the degree of acquired thermotolerance restored to the Synechococcus complementation strains.

Angiotensin-converting enzyme gene polymorphism influences degree of left ventricular hypertrophy and its regression in patients undergoing operation for aortic stenosis.

Insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with increased left ventricular hypertrophy (LVH) in patients with cardiomyopathy and congestive heart failure. Patients with aortic stenosis (AS) have varying degrees of LVH at a given valve area. The aim of this study was to examine the relation between ACE gene polymorphism and the degree of LVH in patients undergoing operation for AS. Eighty-two patients who underwent operation for AS with a stentless valve were followed prospectively with echocardiographic assessments of left ventricular mass index (LVMI). ACE gene polymorphism was determined by polymerase chain reaction. The genotype (DD, ID, and II) frequency was the same as in healthy controls. The pressure difference across the aortic valve did not differ between genotypes. Patients with the DD genotype of the ACE gene had a higher LVMI (197 +/- 47 g/m2) preoperatively than those with ID (175 +/- 41 g/m2) or II (155 +/- 43 g/m2) genotypes (p = 0.01). LVMI decreased significantly in DD (p <0.001) and ID (p <0.001) genotypes but not in the II genotype during follow-up (mean 15 months). There was a significant difference in regression of LVMI over time between genotypes (p = 0.0056), with no significant difference between genotypes at follow-up. The DD genotype of the ACE gene is associated with increased preoperative LVH in patients treated surgically for AS. The DD genotype appears to be an important factor which increases hypertrophic myocardial reactivity to pressure overload.

Temporal variability of exercise Doppler echocardiography in patients with nonstented aortic bioprostheses.

Temporal variability and reproducibility of Doppler-derived variables obtained during supine symptom-limited exercise was investigated in 26 patients who were in clinically and hemodynamically stable condition with normally functioning nonstented aortic bioprostheses (stentless porcine, n = 13; cryopreserved homografts, n = 13). All patients had normal systolic left ventricular function and underwent 2 similar exercise tests within 12 months (mean time interval 7.2 +/- 1.9 months). The coefficient of variation was 8% to 9% for primary Doppler-derived variables (ie, velocities and velocity time integrals) at rest and during exercise. The coefficient of variation for calculated maximal pressure difference was 16% at rest and 15% at peak exercise. Measurement variability assessed from repeated measurements from the same videotaped recording was approximately 2%. High reproducibility was shown for most variables with intraclass correlation coefficients of 0.85 or more. We conclude that Doppler echocardiography can be used in patients with nonstented aortic bioprostheses with the same high reproducibility during exercise as at rest. The results provide clinically useful information regarding temporal variability for Doppler-derived variables.

Effects of exercise on Doppler-derived pressure difference, valve resistance, and effective orifice area in different aortic valve prostheses of similar size.

The effects of increased transvalvular volume flow on Doppler-derived measurements were compared in similarly sized, normally functioning, mechanical prostheses, stented and stentless porcine bioprostheses, and homografts. Homograft and stentless valves showed the largest effective orifice area and the lowest pressure differences and valve resistance at rest and during exercise-induced increase in flow rates.

Hemodynamic performance of cryopreserved aortic homograft valves during midterm follow-up.

OBJECTIVES: The aim of this prospective study of adult patients operated with a cryopreserved aortic homograft was to use serial echocardiographic data to evaluate the postoperative hemodynamic performance of these valves. BACKGROUND: Only limited data on hemodynamic performance of aortic homografts at rest and during exercise are available. Controversy also exists regarding incidence and progression of aortic regurgitation (AR). METHODS: Fifty-nine patients aged 39-86 years who received an aortic homograft (median size 21 mm) implanted with subcoronary technique were studied with serial Doppler-echocardiography (D-E). In 31 of these patients, D-E also was performed during supine exercise. RESULTS: Overall survival was 100% during a median follow-up of 28 months (range 4-54). During follow-up AR grade II or more was detected in 25% of the patients with an increasing time-related risk of developing AR. Maximum and mean pressure differences at 7 months follow-up calculated with the short form of the Bernoulli equation were 11.4 (4.6) and 5.5 (2.1) mm Hg, respectively. During supine exercise that increased cardiac output 72%, maximum pressure difference increased from 11.9 (5.2) to 18.5 (9.5) mm Hg. CONCLUSIONS: The aortic homograft valve shows low pressure differences at rest and during exercise, but AR grade I or II is often seen during follow-up. As AR progresses with time we stress the importance of echocardiographic follow-up of patients with aortic homografts.

The cyanobacterium Synechococcus resists UV-B by exchanging photosystem II reaction-center D1 proteins.

Current ambient UV-B levels can significantly depress productivity in aquatic habitats, largely because UV-B inhibits several steps of photosynthesis, including the photooxidation of water catalyzed by photosystem II. We show that upon UV-B exposure the cyanobacterium Synechococcus sp. PCC 7942 rapidly changes the expression of a family of three psbA genes encoding photosystem II D1 proteins. In wild-type cells the psbAI gene is expressed constitutively, but strong accumulations of psbAII and psbAIII transcripts are induced within 15 min of moderate UV-B exposure (0.4 W/m2). This transcriptional response causes an exchange of two distinct photosystem II D1 proteins. D1:1 is encoded by psbAI, but on UV-B exposure, it is largely replaced by the alternate D1:2 form, encoded by both psbAII and psbAIII. The total content of D1 and other photosystem II reaction center protein, D2, remained unchanged throughout the UV exposure, as did the content and composition of the phycobilisome. Wild-type cells suffered only slight transient inhibition of photosystem II function under UV-B exposure. In marked contrast, under the same UV-B treatment, a mutant strain expressing only psbAI suffered severe (40%) and sustained inhibition of photosystem II function. Another mutant strain with constitutive expression of psbAII and psbAIII was almost completely resistant to the UV-B treatment, showing no inhibition of photosystem II function and only a slight drop in electron transport. In Synechococcus the rapid exchange of alternate D1 forms, therefore, accounts for much of the cellular resistance to UV-B inhibition of photosystem II activity and photosynthetic electron transport. This molecular plasticity may be an important element in community-level responses to UV-B, where susceptibility to UV-B inhibition of photosynthesis changes diurnally.

Rest and exercise hemodynamics of an extended stentless aortic bioprosthesis.

BACKGROUND AND AIMS OF THE STUDY: Aortic valve surgery in patients with a narrow aortic root remains a clinical problem. The Extended Biocor Stentless porcine bioprosthesis was specifically designed to allow widening of the aortic annulus in patients with narrow aortic roots. The aim of this prospective study was to evaluate the hemodynamic performance of this prosthesis. METHODS: Serial Doppler echocardiography was used in 50 patients (mean age 77 years, range: 60 to 87 years) during a 15-month follow up after aortic valve replacement. Valve hemodynamics were also assessed in 30 patients at 15 months after surgery, during increased flow rates induced by a supine bicycle exercise test. RESULTS: Of these patients, 60% received valves sized 23 mm or smaller. The mean pressure difference before hospital discharge was 13.8 +/- 5.8 mmHg and this decreased by 40% during the first six months. During the same period there was a significant increase in effective orifice area and a decrease in left ventricular mass. Symptom-limited supine exercise increased cardiac output by 65% while the mean pressure difference increased only slightly (from 8.1 +/- 3.2 to 11.9 +/- 3.6 mmHg). Trivial aortic regurgitation (grade 1+) was detected in 12% of patients at 15 months follow up. All patients who were in NYHA functional class III or IV before surgery were in class I or II after surgery. CONCLUSIONS: We conclude that the Extended Biocor Stentless prosthesis shows low Doppler-derived transvalvular pressure gradients both at rest and during exercise, and also when small-sized valves are employed. Doppler echocardiography, showing low incidence of aortic regurgitation and early regression of left ventricular hypertrophy, demonstrate the beneficial hemodynamic performance of this valve.

The heat shock protein ClpB mediates the development of thermotolerance in the cyanobacterium Synechococcus sp. strain PCC 7942.

The heat shock protein CIpB (HSP100) is a member of the diverse group of Clp polypeptides that function as molecular chaperones and/or regulators of energy-dependent proteolysis. A single-copy gene coding for a ClpB homolog was cloned and sequenced from the unicellular cyanobacterium Synechococcus sp. strain PCC 7942. The predicted polypeptide sequence was most similar to sequences of cytosolic ClpB from bacteria and higher plants (i.e., 70 to 75%). Inactivation of clpB in Synechococcus sp. strain PCC 7942 resulted in no significant differences from the wild-type phenotype under optimal growth conditions. In the wild type, two forms of ClpB were induced during temperature shifts from 37 to 47.5 or 50 degrees C, one of 92 kDa, which matched the predicted size, and another smaller protein of 78 kDa. Both proteins were absent in the delta clpB strain. The level of induction of the two ClpB forms in the wild type increased with increasingly higher temperatures, while the level of the constitutive ClpC protein remained unchanged. In the delta clpB strain, however, the ClpC content almost doubled during the heating period, presumably to compensate for the loss of ClpB activity. Photosynthetic measurements at 47.5 and 50 degrees C showed that the null mutant was no more susceptible to thermal inactivation than the wild type. Using photosynthesis as a metabolic indicator, an assay was developed for Synechococcus spp. to determine the importance of ClpB for acquired thermotolerance. Complete inactivation of photosynthetic oxygen evolution occurred in both the wild type and the delta clpB strain when they were shifted from 37 directly to 55 degrees C for 10 min. By preexposing the cells at 50 degrees C for 1.5 h, however, a significant level of photosynthesis was retained in the wild type but not in the mutant after the treatment at 55 degrees C for 10 min. Cell survival determinations confirmed that the loss of ClpB synthesis caused a fivefold reduction in the ability of Synechococcus cells to develop thermotolerance. These results clearly show that induction of ClpB at high temperatures is vital for sustained thermotolerance in Synechococcus spp., the first such example for either a photosynthetic or a prokaryotic organism.

The cyanobacterium Synechococcus sp. PCC 7942 possesses a close homologue to the chloroplast ClpC protein of higher plants.

The Clp family consists of large, ubiquitous proteins that function as molecular chaperones and/or regulators of ATP-dependent proteolysis. A single copy gene coding for one of these proteins, ClpC, was cloned from the unicellular cyanobacterium Synechococcus sp. PCC 7942. The predicted polypeptide is most similar (ca. 88%) to the chloroplast-localized ClpC protein from higher plants. Using degenerate PCR primers specific for the two distinct ATP-binding domains characteristic of all ClpA-C proteins, partial sequences homologous to clpC from Synechococcus were also identified in five other cyanobacterial strains. The Synechococcus clpC gene is transcribed under standard growth conditions as a monocistronic message of around 2.7 kb. The level of this message, however, decreases slightly after a shift from 37 to 47.5 degrees C for 2 h, similar to expression previously observed for clpC mRNA from heat-shocked higher plants. At the protein level, the amount of ClpC remains relatively unchanged during the high temperature shift, while that of the known heat shock protein GroEL rises considerably. In contrast, the constitutive level of ClpC in Synechococcus increases considerably under conditions of rapid growth, both with increasing light intensities or CO2 concentrations. This, and the fact that attempts to inactivate clpC expression fail to produce a viable phenotype, suggest that ClpC activity is essential for growth in this obligate photoautotrophic cyanobacterium.