Relationship of physical activity with physical function and health-related quality of life in patients having undergone allogeneic haematopoietic stem-cell transplantation.

In this study, we investigated the differences in physical activity before and after transplantation, and the relationship between physical activity and physical function and health-related quality of life (QOL) in 30 patients who underwent allogeneic haematopoietic stem cell transplantation (allo-HSCT). Duration and intensity of physical activity were quantified using a three-dimensional accelerometer. Physical function was quantified by handgrip and knee-extensor strength, with the 6-minute walk test (6MWT) used as a measure of exercise capacity. Health-related QOL was assessed using the 36-item Short-Form Health Survey. The proportion of daily activities performed at an intensity >3.0 metabolic equivalents (METs) increased significantly after allo-HSCT (p < .05). Daily activity time performed at an intensity of 1.6-2.9 METs significantly correlated only with left knee strength (p < .05). In contrast, the total number of daily steps and the proportion of activity performed at 1.6-2.9 METs and >3.0 METs were positively correlated with the 6MWT (p < .05). Additionally, physical functioning and general health subscales in health-related QOL positively correlated with daily activities performed at >3.0 METs (p < .05). Physical activity was associated with 6MWT and health-related QOL. These findings have implications for rehabilitation planning for patients undergoing allo-HSCT.

NOTCH1 expression predicts patient prognosis in esophageal squamous cell cancer.

PURPOSE: The prognosis of patients with esophageal cancer remains poor, and the classification of tumor node metastasis has proven insufficient to predict patient prognosis. Therefore, novel predictive markers of esophageal cancer prognosis are needed. Notch receptors and their ligands have been reported to be upregulated in cervical, lung, colon, renal, and pancreatic cancers, but NOTCH1 expression has not been studied in esophageal cancer. METHODS: Expression of NOTCH1 was quantified by real-time reverse transcription-polymerase chain reaction in 55 primary esophageal squamous cell carcinomas (ESCCs) and their paired normal esophageal mucosa. We then examined the correlations between NOTCH1 expression, clinicopathological factors, and prognosis in patients with ESCC. RESULTS: The probability of overall survival was significantly lower for patients with high NOTCH1 expression (p = 0.0028; log-rank test). Overexpression of NOTCH1 was identified as a significant and independent prognostic factor (p = 0.0061) in patients who had undergone surgical treatment for ESCCs. The hazard ratio for predicting early death was 4.298 (95% confidence interval 1.515-12.195) for high versus low NOTCH1 expression. CONCLUSIONS: Our data indicate that NOTCH1 may be a candidate molecular prognostic marker and a molecular target for the development of an effective therapeutic intervention for patients with ESCC.

Expression of epidermal growth factors and a tight junction protein in the nasal mucosa of patients with chronic hypertrophic rhinitis.

BACKGROUND: ErbB family receptors and tight junction proteins participate in the pathologic process including tissue remodelling of inflammatory diseases in the upper and lower respiratory tracts. This study aimed at investigating the expressions of erbB1, 2, 3, 4, and a tight junction protein, claudin-1, in the nasal mucosa of patients with chronic hypertrophic rhinitis. METHODS: Inferior turbinates were collected from 10 turbinectomised patients with allergic and non-allergic chronic hypertrophic rhinitis. The expressions of erbB1, 2, 3, 4, and claudin-1 were examined by fluorescence immunohistochemistry and by quantitative real-time transcription-polymerase chain reaction (qRT-PCR). RESULTS: All erbB1-4 and claudin-1 were detected, and mainly localised in the epithelial cells and nasal gland cells. The immunoreactivity for claudin-1 was positively correlated with the expressions of erbB1, 2 and 4, but negatively correlated with that of erbB3. The mRNA expressions of erbB1, 2 and 4 were positively correlated with one another, whereas the expression of erbB3 showed negative correlation with the immunoreactivity for erbB2 and 4. CONCLUSIONS: These results suggest a possible participation of erbBs and claudin-1 in tissue remodelling in chronic hypertrophic rhinitis.

ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes.

Zinc-finger protein 143 (ZNF143) is a human homolog of Xenopus transcriptional activator staf that is involved in selenocystyl tRNA transcription. We previously showed that ZNF143 expression is induced by treatment with DNA-damaging agents and that it preferentially binds to cisplatin-modified DNA. In this study, the potential function of ZNF143 was investigated. ZNF143 was overexpressed in cisplatin-resistant cells. ZNF143 knockdown in prostate cancer caused increased sensitivity for cisplatin, but not for oxaliplatin, etoposide and vincristine. We also showed that ZNF143 is associated with tumor suppressor gene product p73 but not with p53. p73 could stimulate the binding of ZNF143 to both ZNF143 binding site and cisplatin-modified DNA, and modulate the function of ZNF143. We provide a direct evidence that both Rad51 and flap endonuclease-1 are target genes of ZNF143 and overexpressed in cisplatin-resistant cells. Taken together, these experiments demonstrate that an interplay of ZNF143, p73 and ZNF143 target genes is involved in DNA repair gene expression and cisplatin resistance.

The complete nucleotide sequence of the tobacco chloroplast genome: its gene organization and expression.

The complete nucleotide sequence (155 844 bp) of tobacco (Nicotiana tabacum var. Bright Yellow 4) chloroplast DNA has been determined. It contains two copies of an identical 25 339 bp inverted repeat, which are separated by a 86 684 bp and a 18 482 bp single-copy region. The genes for 4 different rRNAs, 30 different tRNAs, 39 different proteins and 11 other predicted protein coding genes have been located. Among them, 15 genes contain introns. Blot hybridization revealed that all rRNA and tRNA genes and 27 protein genes so far analysed are transcribed in the chloroplast and that primary transcripts of the split genes hitherto examined are spliced. Five sequences coding for proteins homologous to components of the respiratory-chain NADH dehydrogenase from human mitochondria have been found. The 30 tRNAs predicted from their genes are sufficient to read all codons if the ;two out of three' and ;U:N wobble' mechanisms operate in the chloroplast. Two sequences which autonomously replicate in yeast have also been mapped. The sequence and expression analyses indicate both prokaryotic and eukaryotic features of the chloroplast genes.

Effects of ML-236b (compactin) on sterol synthesis and low density lipoprotein receptor activities in fibroblasts of patients with homozygous familial hypercholesterolemia.

We studied biochemical genetics of low density lipoprotein (LDL) receptor mutations in fibroblasts from six homozygous and five heterozygous patients with familial hypercholesterolemia (FH). Three of six homozygotes are receptor-negative type and the other three homozygotes are receptor-defective type. In the cells from three receptor-negative homozygotes, the receptor binding, internalization, and degradation of (125)I-LDL were 0.5+/-0.3 ng/mg protein (mean+/-SEM), 14+/-8 and 8+/-6 ng/mg protein per 6 h (four normal cells; 44+/-3, 386+/-32, and 1,335+/-214 ng/mg protein per 6 h), respectively. In the cells from three receptor-defective homozygotes, the receptor binding, internalization, and degradation of (125)I-LDL were 6+/-2, 29+/-8, and 90+/-32 ng/mg protein per 6 h, respectively. In these six homozygotes, two pairs of siblings are included. Two siblings in the same family were classified as receptor-negative and two siblings in another family were classified as receptor-defective. The receptor-negative phenotypes and the receptor-defective phenotypes bred true in individual families. The cells from five heterozygotes showed approximately 46% of the normal activities of receptor.ML-236B, competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), completely inhibited the incorporation of [(14)C]acetate into digitonin-precipitable sterols in fibroblasts from normal subjects and heterozygous and homozygous patients with FH with the concentration of 0.5 mug/ml. However, at 0.05 mug/ml of ML-236B sterol synthesis in fibroblasts from homozygotes was not completely suppressed in contrast to normal and heterozygous cells. Moreover, after preincubation with 0.05 mug/ml of ML-236B for 24 h in medium containing lipoproteins, sterol synthesis in the cells from receptor-negative homozygote showed 75% of the initial activity compared with that of 25% without preincubation. In the cells from a normal subject and a heterozygote, sterol synthesis was inhibited even after preincubation. These results suggest that (a) the inhibitory effect of ML-236B is overcome in homozygote cells by their high intracellular levels of HMG-CoA reductase and (b) that a higher dose of ML-236B may be required to lower serum cholesterol levels in FH homozygotes than in heterozygotes.

Quantitative rest technetium-99m tetrofosmin imaging in predicting functional recovery after revascularization: comparison with rest-redistribution thallium-201.

OBJECTIVES: This study was undertaken to 1) compare the regional myocardial tracer distributions between rest technetium (Tc)-99m tetrofosmin and rest-redistribution thallium (Tl)-201 images in patients with coronary artery disease and left ventricular dysfunction; and 2) assess the comparative values of these agents for predicting functional recovery after revascularization. BACKGROUND: Tc-99m tetrofosmin is a new myocardial perfusion imaging agent, but its role for detecting viable myocardium is still unclear. METHODS: Thirty-six patients with coronary artery disease and left ventricular dysfunction underwent rest Tc-99m tetrofosmin, rest-redistribution Tl-201 and gated blood pool scintigraphy. In 21 patients with successful revascularization confirmed by follow-up angiography, gated blood pool scintigraphy was repeated after revascularization. Optimal threshold cutoffs to separate reversible from irreversible dysfunction were determined by receive operating characteristic analysis. RESULTS: Regional Tc-99m tetrofosimin activity highly correlated with redistribution Tl-201 activity (r = 0.93). The diagnostic performance for predicting functional recovery, as measured by the area under the receiver operating characteristic curves, measured 0.66 +/- 0.07 (mean +/- SD) for Tc-99m tetrofosmin and 0.67 +/- 0.07 for Tl-201 (p = 0.60, 96.7% power to detect difference in area of 0.10). The optimal threshold cutoffs for viability were considered to be 50% of peak activity for Tc-99m tetrofosmin and 55% of peak activity for Tl-201. The positive and negative predictive values for reversible dysfunction were, respectively, 69% and 82% for Tc-99m tetrofosmin and 69% (p = 0.99 vs. Tc-99m tetrofosmin) and 71% (p = 0.66 vs. Tc-99m tetrofosmin) by Tl-201. CONCLUSIONS: The diagnostic performance of quantitative rest Tc-99m tetrofosmin imaging in predicting functional recovery after revascularization is comparable to that of rest-redistribution Tl-201.

Nucleotide sequence of a putative sensory kinase gene from the cyanobacterium, Anacystis nidulans 6301.

The nucleotide sequence of a 2,146 bp portion of the Anacystis nidulans (Synechococcus PCC6301) genome has been determined. This region contains an open reading frame (ORF) of 392 codons, whose predicted protein sequence shows partial homology to those of E. coli phoM and envZ. Hence ORF392 is suggested to be a sensory kinase gene in cyanobacteria.

The chloroplast gene for ribosomal protein CL23 is functional in tobacco.

Chloroplast rpl23 loci potentially coding for a polypeptide homologous to the E. coli L23 ribosomal protein are frame-shifted in spinach and several other plants, indicating that these loci are pseudogenes. In tobacco, rpl23 constitutes a continuous open reading frame of 93 codons and its transcript initiates at least 66 bp upstream from the initiation codon. The N-terminal amino acid sequence of a 13 kDa protein from the 50 S subunit of tobacco chloroplast ribosomes matches that derived from the tobacco rpl23 locus. This shows that rpl23 is a functional gene in tobacco.

The chloroplast infA gene with a functional UUG initiation codon.

All chloroplast genes reported so far possess ATG start codons and sometimes GTGs as an exception. Sequence alignments suggested that the chloroplast infA gene encoding initiation factor 1 in the green alga Chlorella vulgaris has TTG as a putative initiation codon. This gene was shown to be transcribed by RT-PCR analysis. The infA mRNA was translated accurately from the UUG codon in a tobacco chloroplast in vitro translation system. Mutation of the UUG codon to AUG increased translation efficiency approximately 300-fold. These results indicate that the UUG is functional for accurate translation initiation of Chlorella infA mRNA but it is an inefficient initiation codon.

Chloroplast ribosomal protein L32 is encoded in the chloroplast genome.

The 50 S subunit of chloroplast ribosomes was prepared from tobacco leaves. The proteins were fractionated and the N-terminal amino acid sequence of a 14 kDa protein was determined. This sequence matches the N-terminal sequence deduced from ORF55 located between ndhF and trnL on the small single-copy region of tobacco chloroplast DNA. The deduced protein shows homology to E. coli and B. stearothermophilus L32 proteins, and it has been named as CL32 and ORF55 as rpl32. The tobacco chloroplast genome therefore contains 21 different ribosomal protein genes.

Causes of death in patients with familial hypercholesterolemia.

Five out of 15 homozygotes and 41 out of 527 heterozygotes of familial hypercholesterolemia (FH) died during the past 10 years. Sudden death or heart failure was the cause of death in each of the 5 deceased homozygotes. Twenty heterozygotes died of myocardial infarction, 9 of sudden death, and 1 died after AC bypass surgery. Thus, 30 heterozygotes (73.2%) died of coronary heart disease (CHD). The mean age of death was significantly younger in male heterozygotes (54 years) than in the females (68 years). Rate of death from CHD in heterozygotes was 11 times higher than in the general population in Japan. Rate of death from pancreas cancer in FH was significantly higher than in the general population. These results suggest that FH is highly associated with pancreas cancer as well as CHD.

Treatment of homozygous patients with familial hypercholesterolemia by double-filtration plasmapheresis.

Two homozygous patients with familial hypercholesterolemia were treated by double-filtration plasmapheresis. The plasma separated by the first filter was subsequently led to the second filter of ethylene vinylalcohol co-polymer hollow fibers, which trap very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and low density lipoprotein (LDL) preferentially to other plasma constituents. Serum, VLDL, IDL, LDL cholesterol levels decreased by 55, 68, 59 and 55%, respectively. HDL cholesterol levels decreased by 39%. Immunoglobulins and fibrinogen levels decreased significantly. Cutaneous and tendinous xanthomas became smaller. off

Effects of CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, on serum lipid and apolipoprotein levels in heterozygous familial hypercholesterolemic patients treated by low density lipoprotein (LDL)-apheresis.

Nine heterozygous patients with familial hypercholesterolemia (FH) were treated by low density lipoprotein (LDL)-apheresis using dextran sulfate cellulose columns. After more than 3 procedures of LDL-apheresis without drug therapy, combination therapy with LDL-apheresis and CS-514 (eptastatin), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme (HMG-CoA) reductase, at a dose of 10 mg twice daily was started. Pre- and post-apheresis serum cholesterol levels were decreased significantly by CS-514, from 289 +/- 24 mg/dl (mean +/- SEM) to 247 +/- 25 mg/dl and from 118 +/- 7 mg/dl to 106 +/- 9 mg/dl, respectively. Pre- and post-apheresis apolipoprotein B levels decreased significantly on CS-514 from 160 +/- 9 mg/dl to 138 +/- 8 mg/dl and from 58 +/- 6 mg/dl to 45 +/- 6 mg/dl, respectively. No adverse effects were observed during the combination therapy. Thus, the addition of an inhibitor of HMG-CoA reductase to LDL-apheresis is a useful method for further reducing serum cholesterol and apolipoprotein B levels in FH heterozygotes.

Serum lipids, lipoprotein lipids and coronary heart disease in patients with xanthelasma palpebrarum.

Serum lipids and lipoprotein lipids were studied in 53 patients (21 males and 32 females) with xanthelasma palpebrarum and 40 age-matched normal controls (20 males and 20 females). Patients were subdivided into patients with normolipidemia, hyperlipidemia or familial hypercholesterolemia (FH). In both male and female patients with hyperlipidemia or FH, the serum cholesterol (Chol) levels were significantly higher than in normal controls. In both male and female patients with normolipidemia or hyperlipidemia, the VLDL-Chol levels were significantly higher than in normal controls. Male patients with FH showed significantly higher levels of VLDL-Chol than normal controls. Both male and female patients with normolipidemia, hyperlipidemia or FH showed significantly higher levels of LDL-Chol, lower HDL-Chol levels and lower HDL-Chol/LDL-Chol ratios than normal controls. In both male and female patients with hyperlipidemia and in male patients with FH, the serum triglyceride (TG) levels were significantly higher than in normal controls. Both male and female hyperlipidemic patients showed significantly higher levels of VLDL-TG than normal controls. In male patients with FH, the VLDL-TG levels were significantly above the control levels. In male patients with normolipidermia, the LDL-TG levels were significantly higher than in normal controls. In both male and female patients with hyperlipidemia or FH, the LDL-TG levels were significantly higher than in normal controls. The HDL-TG levels in patients with normolipidemia (males) or FH (females) were significantly lower than in normal controls. The prevalence of coronary heart disease in patients with normolipidemia, hyperlipidemia or FH was 29.4%, 24.0% and 45.4%, respectively.

Improved myocardial fatty acid utilization after percutaneous transluminal coronary angioplasty.

Exercise-reinjection 201Tl imaging and resting 20-min and 3-hr BMIPP imaging were performed before and 4 mo after percutaneous transluminal coronary angioplasty (PTCA) in a patient with effort angina. Before PTCA, exercise 201Tl imaging showed decreased 201Tl activity in the septal wall, with significant fill-in on the reinjection 201Tl image. The resting 20-min BMIPP image showed decreased activity in the septal wall, with a slight redistribution on the 3-hr BMIPP image. The 201Tl and BMIPP images 4 mo after PTCA showed significant improvement in the 201Tl pattern and BMIPP uptake in the septal wall with no abnormally decreased activities.

Myocardial viability assessment with technetium-99m-tetrofosmin and thallium-201 reinjection in coronary artery disease.

UNLABELLED: Exercise-rest 99mTc-tetrofosmin myocardial perfusion images with a 2-day protocol was compared to exercise-redistribution-reinjection 201Tl images to assess the ability of 99mTc-tetrofosmin to detect viable myocardium. METHODS: We studied 25 patients with coronary artery disease and regional or global left ventricular dysfunction. Myocardial SPECT images with 99mTc-tetrofosmin were obtained 10 min after injection during exercise and 1 and 3 hr after rest injection. Within 1 wk of the 99mTc-tetrofosmin study, exercise-redistribution-reinjection 201Tl SPECT imaging was performed. RESULTS: Visual analysis demonstrated concordance between 201Tl and 99mTc-tetrofosmin imaging for defect reversibility in 126 of 209 segments (60%), with initial defects on both exercise 201Tl and 99mTc-tetrofosmin images. In the remaining discordant 83 segments (40%), 73 (88%) appeared nonreversible on 99mTc-tetrofosmin imaging but were reversible on 201Tl imaging. CONCLUSION: On the basis of defect reversibility by visual analysis, exercise-rest 99mTc-tetrofosmin imaging underestimates myocardial viability compared to 201Tl reinjection imaging. The identification of viable myocardium with both 99mTc-tetrofosmin and 201Tl can be greatly enhanced to a similar degree if the severity of reduction in activity within nonreversible defects is considered. These two agents may provide comparable information about myocardial viability by quantitative analysis of defect severity.

Significance of late redistribution thallium-201 imaging after rest injection for detection of viable myocardium.

UNLABELLED: The aim of this study was to determine whether late redistribution imaging after rest injection of 201Tl would provide further information on myocardial viability over conventional rest-early redistribution 201Tl imaging. METHODS: Twenty-nine patients with coronary artery disease and left ventricular dysfunction underwent rest, early (3-4 hr) and late (20-24 hr) redistribution 201Tl and gated blood pool studies. In 14 patients with successful revascularization, gated blood pool study was repeated after the coronary intervention. RESULTS: Nine of 29 patients showed early redistribution, and six additional patients showed further redistribution on the late images. Of 136 segments with initial 201Tl defects, 18 showed early redistribution, and 10 showed late redistribution. When a threshold of 60% of peak activity was used as an index of myocardial viability, only a small fraction (3%) of the initial 201Tl defects were additionally considered viable by the late images. In 14 patients who underwent revascularization, the positive (69%) and negative (87%) predictive values of the early redistribution images for functional recovery were similar to those obtained by the late images (68% and 86%, respectively). CONCLUSION: Although late redistribution after rest injection of 201Tl occasionally occurs, most of the clinically relevant information on myocardial viability may be obtained by conventional rest-early redistribution 201Tl imaging when the defect severity is considered an index of tissue viability.

Kinetics of iodine-123-BMIPP in patients with prior myocardial infarction: assessment with dynamic rest and stress images compared with stress thallium-201 SPECT.

UNLABELLED: Myocardial kinetics of 123I-labeled 15-(p-iodophenyl)3R, S-methylpentadecanoic acid (BMIPP) were evaluated with dynamic SPECT, and stress and rest BMIPP images were directly compared in conjunction with stress 201Tl. METHODS: We studied 26 patients with prior myocardial infarction. Two minutes after injection of BMIPP, dynamic data acquisition with a three-headed SPECT was started and continued for 12 min. Conventional SPECT images were obtained at 20 min and 3 hr after injection. On a separate day, exercise, stress 201Tl SPECT was performed at 10 min and 3 hr after injection. Exercise stress-BMIPP imaging was performed in 15 of the patients, and static SPECT images were obtained. RESULTS: With dynamic SPECT, early clearance of BMIPP from the myocardium was observed in the segments with reversible 201Tl defects, suggesting enhanced contribution of backdiffusion from BMIPP. In myocardial segments with reversible 201Tl defects, 20-min BMIPP images showed a higher frequency of reduced uptake when compared to 3-hr 201Tl (90/163) imaging. CONCLUSION: With BMIPP dynamic SPECT, an enhanced contribution of backdiffusion in the early phase from ischemic myocardium was suggested. When exercise stress BMIPP images were obtained, a more severe defect was observed than on rest BMIPP and stress 201Tl imaging, possibly due to decreased coronary blood flow and impaired fatty acid uptake induced by ischemia during exercise.

Comparison of defect size between thallium-201 and technetium-99m tetrofosmin myocardial single-photon emission computed tomography in patients with single-vessel coronary artery disease.

Defect size on exercise-rest technetium (Tc)-99m tetrofosmin myocardial perfusion imaging was compared with that on exercise-reinjection thallium-201 imaging with 20 patients with 1-vessel coronary artery disease. In each patient, exercise-reinjection thallium-201 single-photon emission computed tomography (SPECT) and exercise-rest Tc-99m tetrofosmin SPECT imaging were performed. For visual analysis of the obtained SPECT images, the left ventricular myocardium was divided into 20 segments based on 3 short-axis slices from the apical, middle, and basal ventricular levels. For quantitative analysis, a square region of interest was placed on the center of each segment which was used for visual analysis, and relative regional activity to the normal reference region was calculated for each segment. By visual interpretation of the images, exercise Tc-99m tetrofosmin imaging showed a smaller defect size than exercise thallium-201 imaging (6.9 +/- 3.9 vs 8.8 +/- 3.0 segments, p <0.01). In contrast, rest Tc-99m tetrofosmin imaging showed a defect size similar to that on reinjection thallium-201 imaging (5.9 +/- 3.6 vs 5.6 +/- 3.9 segments, p = NS). Similarly, the mean defect sizes during exercise determined by quantitative analysis were smaller on Tc-99m tetrofosmin SPECT than those on thallium-201 SPECT at all tested threshold cutoff points ranging from 50% to 70%, whereas there were no significant differences in defect sizes between rest Tc-99m tetrofosmin and reinjection thallium-201 imaging. These data indicate that exercise Tc-99m tetrofosmin SPECT defect size determined either by visual analysis or by quantitative analysis may be smaller than on exercise thallium-201 SPECT.