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PubMed1991

Heterogenous expression of decay accelerating factor and CD59/membrane attack complex inhibition factor on paroxysmal nocturnal haemoglobinuria (PNH) erythrocytes.

In order to clarify the characterization of phenotypes of paroxysmal nocturnal haemoglobinuria (PNH) erythrocytes (E), we analysed the expression of decay accelerating factor (DAF) and CD59/membrane attack complex inhibition factor (MACIF) on the membrane surface of PNH-E by means of the flow cytometric method using anti-DAF and/or CD59/MACIF monoclonal antibodies in nine PNH-patients. In two-colour analysis, this expression of PNH-E was classified into three fractions; negative, intermediate and positive according to intensity. The negative fraction was classified into two groups; one group an exclusively negative population, and the other a negative population having slightly DAF-positive E. The intermediate fraction was recognized on PNH-E of cases with PNH II-E and extremely heterogenous. In the positive fraction, this expression was almost the same as on normal E except for case 8. In single-colour analysis for DAF or CD59/MACIF, three fractions were classified as well as the definition in two-colour analysis. In single-colour analysis, the expression on PNH-E was also heterogenous in each fraction and among PNH-patients. However, the intermediate fraction for CD59/MACIF was not found on PNH-E of cases without PNH II-E, although intermediate fraction for DAF was recognized on PNH-E of some cases with PNH III-E in addition to those with PNH II-E. The results suggest that expression of CD59/MACIF and DAF on the membrane surface of PNH-E phenotypes is heterogenous and varies among PNH patients.

Adult↗
PubMed2006

To what extent does the prostate-specific antigen nadir predict subsequent treatment failure after transrectal high-intensity focused ultrasound therapy for presumed localized adenocarcinoma of the prostate?

OBJECTIVE: To explore the association between the prostate-specific antigen (PSA) nadir after transrectal high-intensity focused ultrasound (HIFU) therapy for organ-confined prostate cancer and subsequent treatment failure, as defined by the presence of residual disease at biopsy 6 months after treatment. PATIENTS AND METHODS: Between January 1999 and January 2005, 115 patients in a Japanese hospital were treated using a transrectal HIFU system (Sonablate, Focus Surgery, IN, USA) for presumed localized adenocarcinoma of the prostate. All treatments were primary and none of the patients had received hormone therapy. The PSA level was measured at 2-monthly intervals and all patients had a transrectal prostate biopsy taken at 6 months. Multiple logistic regression was used to examine the relationship between PSA nadir and treatment failure, as defined by the presence of disease at biopsy. RESULTS: The PSA nadir was strongly associated with treatment failure (P < 0.001). Patients with a PSA nadir of 0.0-0.2 ng/mL had a treatment failure rate of only 11% (four of 36), compared to 46% (17 of 37) in patients with a PSA nadir of 0.21-1.00 ng/mL and 48% (20 of 42) with a PSA nadir of >1.0 ng/mL. In addition, the PSA nadir was strongly associated with both preoperative PSA level and residual prostate volume. CONCLUSION: There is a clear and intuitive association between the PSA nadir and the risk of treatment failure after HIFU. These data can be used to predict the risk of residual disease in patients with prostate cancer undergoing HIFU therapy. They can also be used to inform where the target PSA nadir should be set for this novel therapy.

Adenocarcinoma↗
PubMed1997

Adjuvant chemotherapy with epirubicin and carmofur after radical resection of hepatocellular carcinoma: a prospective randomized study.

The intrahepatic recurrence rate is extremely high, even after radical resection of hepatocellular carcinoma (HCC). One report showed intra-arterial administration of epirubicin to be effective in the treatment of nonresectable HCC. We evaluated the effect of postoperative adjuvant chemotherapy including this drug. Fifty-seven patients who had undergone radical resection of HCC were entered in this study. Using the sealed-envelope method, 27 patients were assigned to a group undergoing resection only and 29 patients to a group also receiving adjuvant chemotherapy after resection. The protocol of the chemotherapy was intra-arterial administration of epirubicin (40 mg/m2) at 1 month after resection followed by intravenous administration of epirubicin (40 mg/m2) every 3 months for 2 years. In addition, 1-hexylcarbamoyl-5-fluorouracil (HCFU; carmofur), 300 mg/d, was administered orally every day, beginning from 1 month after the resection and continuing (in principle) for 24 months. The clinicopathologic backgrounds were well randomized between the two groups. The chemotherapy protocol was performed completely in only five patients (7.2%). Twenty-four (82.8%) patients had to cease the protocol due to various reasons: change to a new therapy after recurrence of HCC in 19 cases (79.2%), severe side effects of the chemotherapy in three cases (12.5%), liver failure in one case (4.2%), and a postoperative complication in one case (4.2%). The mean total doses were 128 +/- 114 mg for epirubicin and 144 +/- 84 g for HCFU. The cumulative overall and disease-free survival rates for 5 years were not significantly different between the two groups. The results of this prospective randomized study suggest that this adjuvant chemotherapy protocol with epirubicin and HCFU after radical resection of HCC was not effective.

Antibiotics, Antineoplastic↗
PubMed1985

Effects of nerve growth factor and heart cell conditioned medium on neurite regeneration of aged sympathetic neurons in culture.

The effects of nerve growth factor (NGF) and heart-cell-conditioned medium (HCM) on the neurite regeneration of aged sympathetic neurons were investigated in culture. Investigation of HCM was carried out by two different methods: one was the use of whole HCM on collagen substratum, which reflected component(s) effective in solution (HCM-S); the other was the use of polyornithine (PORN)-binding component(s) (P-HCM). Superior cervical ganglion neurons prepared from male mice from 6 to 30 months of age were cultured in MEM-10% FCS on collagen or gelatin-PORN substratum for 3 days. The number of neurons with neurites and the length of neurites were quantified as neurite production and elongation, respectively. Neuronal survival was not affected by addition of NGF, HCM-S or P-HCM. Neurite production of early adult neurons was enhanced by NGF, HCM-S or P-HCM. In contrast, neurite production of aged neurons was enhanced by only HCM-S, but not NGF or P-HCM. HCM-S did not promote neurite elongation in neurons at any age. Neurite elongation of early adult neurons was enhanced by NGF or P-HCM. Neurite elongation of aged neurons was enhanced by P-HCM. However, responsiveness of NGF for neurite elongation varied according to substrata. No age-related difference was found in neurite production and elongation in the absence of NGF, HCM-S or P-HCM. These results indicate that responsiveness of aged sympathetic neurons is various in different growth factors.

Age Factors↗
PubMed1986

High-performance liquid chromatographic determination of 6,8-difluoro-1-(2-fluoroethyl)-1,4- dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid and its metabolites in laboratory animals.

A simple, sensitive and specific high-performance liquid chromatographic method for a new quinolone antimicrobial agent, 6,8-difluoro-1-(2-fluoroethyl)-1,4- dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylic acid (AM-833, I), and its metabolites in serum and urine has been developed for their simultaneous determination. This method is based on ion-pair extraction and separation by ion-pair reversed-phase chromatography with ultraviolet or fluorescence detection. The major metabolites in the serum and urine of mice, rats, dogs and monkeys were N-desmethyl I (compound II) and I N-oxide (compound III). Rabbit serum and urine contained N-desmethyl-3-oxo I (compound IV), 3-oxo I (compound V) and N-desmethyl-4-formyl I (compound VI) in addition to compounds I, II and III. Unchanged drug accounted for 80-90% of total serum concentrations in mice and more than 90% in rats, dogs and monkeys up to 6 h after dosing, whereas the fraction of compound I in rabbits was 34-67%. Unchanged drug was the most predominant in the urine of mice, rats, dogs and monkeys, whereas compound II was the most abundant in rabbit urine. Although rabbits and monkeys excreted 70-80% of dose in three-day urine, the total urinary excretion of mice, rats and dogs was relatively low, 40-50% of oral dose. The fraction of compound I in total urinary excretion was 63, 73, 27, 55 and 78% in mice, rats, rabbits, dogs and monkeys, respectively. These results suggest that there is a species difference in the metabolism and excretion pathway of compound I.

Animals↗
PubMed2002

Increased serum cholesteryl ester transfer protein in obese children.

OBJECTIVE: To determine whether serum cholesteryl ester transfer protein (CETP), which is one of the physiologically active gene products secreted from adipose tissue, is increased and associated with atherogenic lipoprotein profile in obese children. RESEARCH METHODS AND PROCEDURES: Subjects were 42 consecutive outpatient Japanese obese children, 29 boys and 13 girls, ranging in age from 5 to 14 years, and 25 age-matched non-obese children, 13 boys and 12 girls, as the control group for measuring CETP mass. Blood was drawn after an overnight fast and, at the same time, and anthropometric measurements including height, body weight, waist girth, hip girth, and triceps and subscapular skinfold thicknesses were taken. Paired samples were obtained from 15 obese children who underwent psychoeducational therapy. Serum CETP mass was assayed by an enzyme-linked immunosorbent assay. RESULTS: The serum levels of triglyceride, total cholesterol (TC), low-density lipoprotein cholesterol, TC/high-density lipoprotein cholesterol (HDLC), apolipoproteins (apo) B, apo B/apo A(1), and insulin in obese children were significantly higher than the respective reference values. Serum CETP level was approximately 2-fold higher (98.7 +/- 3.6 vs. 50.9 +/- 4.0 nM, means +/- SEM, p < 0.001) in the obese children than in the controls. In 15 obese children, whose percentage of overweight declined during therapy, CETP levels decreased significantly. CETP level was correlated with HDLC, TC/HDLC, and insulin, and with percentage of overweight when the data of the obese and non-obese children were combined. DISCUSSION: CETP is increased and associated with the atherogenic lipoprotein profile in obese children.

Adolescent↗
PubMed2000

Lymphatic drainage of carbon particles injected into the pleural cavity of the monkey, as studied by video-assisted thoracoscopy and electron microscopy.

OBJECTIVES: The aim of this study was to clarify the dynamics of lymphatic drainage of the pleural cavity to understand the mechanism of malignant pleural effusion. METHODS: We injected carbon particles into the pleural cavity of monkeys subjected to general anesthesia. We then observed the parietal pleura with a video-assisted thoracoscope and scanning and transmission electron microscopes to examine the regions of the parietal pleura where the carbon particles had been absorbed. RESULTS: The video-assisted thoracoscope showed that the carbon particles had gone directly to the costal, mediastinal, and diaphragmatic pleura by 10 to 15 minutes after injection. From the scanning and transmission electron microscopes, we found that the parietal pleura in the costal and mediastinal regions consisted of 3 elements: a layer of small mesothelial cells, the macula cribriformis, and lymphatic lacunae. Stomata (3-5 microm in diameter) were found between the small mesothelial cells. The macula cribriformis was composed of densely packed collagen fibrils and had many foramina (3-10 microm in diameter). Intrapleurally injected carbon particles were carried into the lymphatic lacunae via the stomata and vesicles of the mesothelial cells and the foramina of the macula cribriformis. The lymphatic lacunae filled with carbon particles were richly distributed in both the anterior costal pleura and the mediastinal pleura. CONCLUSION: We suggest that the mesothelial stomata and the macula cribriformis are structures essential to the absorption of macromolecules and cellular elements from the pleural cavity into the lymphatic system.

Animals↗
PubMed2005

Glucosylceramide accumulates preferentially in lamellar bodies in differentiated keratinocytes.

BACKGROUND: Sphingolipids, e.g. ceramide (Cer), glucosylceramide (GlcCer) and sphingomyelin (SM), are important bulk constituents of plasma membranes in mammalian cells. In addition, these lipids are also enriched in certain intracellular organelles, as well as in the epidermal lamellar bodies (LBs) of differentiating keratinocytes (KCs). Epidermal Cer, which comprises a heterogeneous family of at least 10 members, is a key component of the stratum corneum (SC) lipids, and regulates permeability barrier function. Levels of GlcCer, but not SM, significantly increase during epidermal differentiation, and then both GlcCer and SM are enzymatically hydrolysed to Cer at and just above the transition from the stratum granulosum to the SC. OBJECTIVES: To determine: (i) whether the GlcCer contained in different pools, i.e. the membrane fraction or the LB fraction, has different metabolic fates; and (ii) whether specific molecular species of GlcCer localize to distinct subcellular pools. METHODS: To study the metabolic fate of specific molecular fractions of GlcCer and Cer, we first ascertained the full spectrum of molecular species present in cultured normal human KCs (CHK) in a differentiated condition as shown in vivo in epidermis. Cer species were analysed in CHK using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Next, the metabolic fate of the GlcCer was studied by pulse-labelling of CHK with L-[14C]-serine. RESULTS: The GlcCer of undifferentiated KCs comprised GlcCer B and Cer NS (or Cer 2), which contain nonhydroxy fatty acid (FA) as the amide-linked FA, while differentiated KCs displayed further heterogeneity of both GlcCer and Cer, including the presence of acylGlcCer and acylCer. The metabolic fates of these sphingolipids were determined. The GlcCer B level decreased over 2 days and then plateaued between days 3 and 5 following pulse-labelling of sphingolipids for 24 h. As GlcCer B declined, Cer NS (Cer 2) increased in a similar time-dependent manner. In contrast, both acylGlcCer and acylCer increased continuously in parallel over this experimental period. CONCLUSIONS: Distinct GlcCer pools segregated to those that were either hydrolysable or nonhydrolysable in differentiated KCs. We assume that the latter pool appears to be LB enriched, and also sequestrates acylGlcCer from other cellular membrane fractions.

Adult↗
PubMed1997

Retrovirus in salivary glands from patients with Sjögren's syndrome.

AIMS: To investigate the possibility of an immune response to retroviral antigens or of detecting retrovirus in Sjögren's syndrome. METHODS: Retroviruses were sought in labial salivary glands and peripheral blood mononuclear cells from patients with Sjögren's syndrome by immunoblotting assay, immunohistochemical assay, polymerase chain reaction (PCR), reverse transcriptase (RT) activity assay, and transmission electron microscopy. RESULTS: Sera from five of 15 patients with Sjögren's syndrome (33%) reacted against p24 group specific antigen (gag) of human immunodeficiency virus (HIV). Labial salivary gland biopsy specimens from seven of the 15 patients with Sjögren's syndrome (47%) contained an epithelial cytoplasmic protein reactive with a monoclonal antibody to p24 of HIV. PCR was performed to detect HIV and human T lymphotropic virus type I (HTLV-I) genes from salivary gland tissues and peripheral blood mononuclear cells from patients with Sjögren's syndrome. Mn2+ dependent, Mg2+ independent RT activity was detected in the salivary gland tissues in three of 10 patients. A-type-like retroviral particles were observed in epithelial cells of salivary glands by transmission electron microscopy. Target genes for HIV and HTLV-I were not found in any of the salivary gland tissues or peripheral blood mononuclear cells from Sjögren's syndrome patients. CONCLUSIONS: The data suggest the presence of an unknown retrovirus similar to HIV in the salivary gland which might be involved in the pathogenesis of a subpopulation in Sjögren's syndrome.

Adult↗
PubMedDate not supplied

Influence of transcatheter arterial chemoembolization on the prognosis after hepatectomy for hepatocellular carcinoma in patients with severe liver dysfunction.

BACKGROUND: The influence of preoperative transcatheter arterial chemoembolization (TACE) on postoperative survival and recurrence of hepatocellular carcinoma (HCC) after resection is still controversial. The effect of preoperative TACE on the prognosis of HCC after hepatectomy in 243 patients with liver dysfunction was evaluated. MATERIALS AND METHODS: Among 243 patients who underwent curative resection of HCC between 1992 and 2005, 124 patients had an indocyanine-green retention rate at 15 min (ICGR15) of <17% (49 underwent TACE), while 119 patients had an ICGR15 of > or =17% (66 underwent TACE). The clinical characteristics, operative results and long-term survival were compared between patients with and without preoperative TACE who had mild or severe liver dysfunction. RESULTS: There was no significant difference in the recurrence-free and overall survival rates between the TACE and no TACE groups with an ICGR15 <17%. Among the 119 patients with an ICGR15 > or =17%, there were no significant differences of preoperative characteristics, operative findings, or histology between the two groups. However, the post-resection disease-free and overall survival rates of 66 patients who underwent TACE were significantly better than those of 53 patients who did not have TACE (p = 0.009 and p = 0.0099, respectively). Using multivariate analysis, preoperative TACE was independently associated with better disease-free and overall survival after resection in patients with an ICGR15 > or =17% (p = 0.0309 and p = 0.0162, respectively). CONCLUSION: Preoperative TACE did not alter the prognosis after resection of HCC in patients with mild liver dysfunction, but it did improve the prognosis of patients with severe liver dysfunction.

Aged↗
PubMed2002

Possible relationship between insulin resistance and remnant-like lipoprotein particles in coronary endothelial dysfunction.

BACKGROUND: High insulin resistance and elevated remnant lipoprotein levels both correlate with impaired coronary vascular endothelial function. Hyperinsulinemia induces abnormalities of lipid metabolism. However, the correlation among insulin resistance, remnant lipoproteins, and endothelial function has not been clinically elucidated. HYPOTHESIS: This study was designed to elucidate the correlation among insulin resistance, remnant lipoproteins, and acetylcholine (ACh)-induced coronary artery response. METHODS: Forty-nine patients suspected of having ischemic heart disease, but without angiographically significant atherosclerotic coronary artery disease, underwent an ACh provocation test. Fasting venous blood was taken early in the morning on the day coronary angiography was performed. The insulin resistance index (IR) was determined from fasting plasma glucose and insulin concentrations, using the homeostasis model assessment (HOMA). Serum levels of remnant-like lipoprotein particle cholesterol (RLP-C) were measured. RESULTS: Homeostasis model assessment IR was significantly higher (3.65 +/- 1.38 vs. 0.75 +/- 0.14, p < 0.05) and log-transformed HOMA (Log HOMA) was even more significantly higher (0.20 +/- 0.12 vs. -0.29 +/- 0.08, p < 0.001) in the ACh-positive group (n = 23) than in the ACh-negative group (n = 26). The serum RLP-C level was also higher in the ACh-positive group than in the ACh-negative group (4.37 +/- 0.63 vs. 2.52 +/- 0.18 mg/dl, p < 0.01). Log HOMA and RLP-C levels correlated with each other (R = 0.54, p < 0.001). Multiple regression analysis indicated that only the RLP-C level was a dependent predictor of Log HOMA in various lipid profiles. CONCLUSIONS: Both high insulin resistance and elevated remnant lipoprotein levels correlated and might have a crucial role in the impairment of coronary vascular endothelial function, even in patients without angiographically significant coronary artery disease.

Acetylcholine↗
PubMed2002

Prognostic value of cyclin B1 in patients with esophageal squamous cell carcinoma.

BACKGROUND: It has been reported that p53 regulates the G2-M checkpoint transition through cyclin B1, and it has been suggested that p53 plays an important role in the development and progression of various malignancies. The objective of the current study was to clarify the role of the cell cycle regulators, cyclin B1 and p53, in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Tissue samples from 71 patients with ESCC were included in the current study. Expression levels of cyclin B1 and p53 in samples of normal squamous epithelium, dysplasia, and tumor cells from patients with ESCC were analyzed by immunohistochemistry. RESULTS: Several cells in the basement layer of normal epithelium expressed cyclin B1. The number of cyclin B1 positive cells tended to increase as the degree of dysplasia increased from low grade to high grade. More than 20% of tumor cells were cyclin B1 positive in 38 patients (49.3%). Several clinicopathologic parameters, including macroscopic configuration (P < 0.01), pathologic tumor status (P < 0.05), pathologic lymph node status (P < 0.001), pathologic metastatic status (P < 0.01), tumor stage (P < 0.0001), and invasion of lymphatic vessels (P < 0.05), were correlated with the overexpression of cyclin B1. Elevated expression levels of cyclin B1 also were correlated with a poor prognosis in patients with ESCC in univariate analysis (P < 0.0001) and multivariate analysis (P = 0.0135). In contrast, p53 expression exhibited no significant correlation with the level of cyclin B1 expression and was not associated with prognostic parameters in patients with ESCC. CONCLUSIONS: These findings suggest that cyclin B1 is involved in the pathogenesis of carcinoma of the esophagus and that elevated levels of cyclin B1 expression, but not p53 expression, may indicate a poor prognosis for patients with ESCC.

Adult↗
PubMed2002

Expression of progastrin-releasing peptide and gastrin-releasing peptide receptor mRNA transcripts in tumor cells of patients with small cell lung cancer.

PURPOSE: Small cell lung cancer (SCLC) is a rapidly growing neoplasm accounting for approximately 20% of patients with lung cancer. Progastrin-releasing peptide (proGRP) is produced in about two-thirds of SCLC tumors and is used as a specific marker for SCLC. Although GRP is known to have a variety of biological functions, only limited information is available concerning expression of proGRP mRNA and protein, and that of the receptor for GRP (GRPR) in SCLC tumors. METHODS: In individuals with SCLC, the levels of serum proGRP(31-98) were measured by enzyme-linked immunosorbent assay. Expression of proGRP as well as GRPR mRNA in SCLC tumor tissues was investigated by reverse transcription-nested polymerase chain reaction (PCR) amplification. The proportions of alternatively spliced proGRP mRNA transcripts were analyzed in proGRP-producing tumors by nested and competitive PCR amplification. Finally, production of proGRP protein in SCLC tumor was evaluated by using immunohistochemical staining with a polyclonal human anti-proGRP antibody. RESULTS: ProGRP mRNA transcripts could be detected only in tumor tissues recovered from individuals with high serum proGRP levels. The proportions of mRNA subtypes in each case were nearly the same, revealing type I of 55.4+/-7.6%, type II with 21-b deletion of 1.8+/-3.6%, and type III with 19-b deletion of 42.8+/-4.3%, respectively. ProGRP protein production was demonstrated in tumor tissues exclusively from individuals exhibiting high serum proGRP levels. In contrast, GRPR mRNA transcripts were detectable in cancer cells from two of five proGRP-expressing tumor tissues. CONCLUSIONS: ProGRP mRNA expression is closely related with the synthesis of proGRP protein which is eventually released into the blood. It is suggested GRP may function as an autocrine growth factor for cancer cells in a subgroup of SCLC patients through, at least in part, upregulation of GRPR expression.

Adult↗
PubMed2005

Local release of C-reactive protein from vulnerable plaque or coronary arterial wall injured by stenting.

OBJECTIVES: The purpose of this study was to assess local release of C-reactive protein (CRP) from atherosclerotic plaques or the vessel wall injured by stenting. BACKGROUND: Recent research has focused on the local production of CRP, especially in inflammatory atherosclerotic plaques. METHODS: The study consisted of two separate protocols. In protocol 1, we measured serum high-sensitivity-CRP (hs-CRP) levels in coronary arterial blood sampled just distal and proximal to the culprit lesions in 36 patients with stable angina and 13 patients with unstable angina. In protocol 2, we measured serial serum hs-CRP levels and activated Mac-1 on the surface of neutrophils in both coronary sinus and peripheral blood in 20 patients undergoing coronary stenting. RESULTS: In protocol 1, CRP was higher in distal blood than proximal blood in both stable (p < 0.05) and unstable angina (p < 0.01). The translesional CRP gradient (distal CRP minus proximal CRP, p < 0.05) as well as the proximal CRP (p < 0.05) and distal CRP (p < 0.05) was higher in unstable angina than in stable angina. In protocol 2, the transcardiac CRP gradient (coronary sinus minus peripheral blood) and activated Mac-1 increased gradually after stenting, reaching a maximum at 48 h (p < 0.001 vs. baseline for both). There was a positive correlation between the transcardiac CRP gradient and activated Mac-1 at 48 h (r = 0.45, p < 0.01). CONCLUSIONS: C-reactive protein is an excellent marker for plaque instability or poststent inflammatory status, and its source might be the inflammation site of the plaque or the coronary arterial wall injured by stenting.

Aged↗
PubMed2001

Clinical significance of antibody against oxidized low density lipoprotein in patients with atherosclerotic coronary artery disease.

OBJECTIVES: This study was designed to establish the clinical significance of antibodies against oxidized low density lipoprotein (anti-Ox-LDL) titer in atherosclerotic coronary artery disease (CAD). BACKGROUND: Oxidative modification of LDL, which plays a key role in the development of atherosclerosis, induces immunogenic epitopes in the LDL molecule, and the presence of anti-Ox-LDL has been demonstrated in human sera. METHODS: Anti-Ox-LDL titer was measured by enzyme-linked immunosorbent assay in 108 patients who had angiographically verified CAD, and 31 patients who had chest pain but no significant CAD, as controls. RESULTS: The anti-Ox-LDL titer was higher (p < 0.01) in patients with multivessel CAD (19.4 +/- 10.1 AcU/ml, n = 68) than in the controls (9.8 +/- 4.1). However, no significant difference was shown between the single-vessel CAD group (15.1 +/- 6.4, n = 40) and the controls, or between the multivessel CAD group and the single-vessel CAD group. The titer was higher in patients with unstable angina (21.5 +/- 11.8 AcU/ml, n = 20, p < 0.01), or in patients with acute myocardial infarction (23.1 +/- 12.0, n = 20, p < 0.01) than in patients with stable-effort angina or old myocardial infarction (12.2 +/- 8.6, n = 68). Multiple logistic regression analysis indicated that the anti-Ox-LDL titer most powerfully discriminated CAD patients from controls (odds ratio [OR]: 1.20, 95% confidence interval [CI]: 1.07-1.33, p = 0.0006) and acute coronary syndrome from chronic CAD (OR: 1.09, 95% CI: 1.04-1.14, p = 0.0008). CONCLUSIONS: Serum anti-Ox-LDL titer not only can predict a presence of atherosclerotic CAD but also may be a marker of plaque instability. Low density lipoprotein oxidation may play an important role in the development of plaque instability.

Aged↗
PubMed2003

New desaturation index to evaluate neonatal apnea using polygraphy.

BACKGROUND: Polygraph recordings of neonatal apnea obtained using an Eden Trace II monitor were manually analyzed to devise a new desaturation index (DSI). METHODS: Heart rate, thoracic respiratory movements, airflow, and blood oxygen saturation (SpO2) of 25 neonates in intensive care were monitored using polygraphy. The DSI was defined as the number of SpO2 decreases per hour of valid monitoring time. Neonates were divided into three groups according to DSI85: group A, DSI85 less than one decrease per hour (n = 12); group B, DSI85 ranging from one to nine decreases per hour (n = 8); and group C, DSI85 > or=10 decreases per hour (n = 5). Clinical characteristics and type of apnea in each group were compared statistically. Group C neonates were treated with aminophylline, and the effects of treatment were evaluated. RESULTS: Gestational age at birth, birthweight, age at monitoring and valid monitoring time did not differ significantly between the three groups, but mean SpO2, DSI70, the frequency of central apnea and periodic breathing did. Oxygen desaturation in group B and particularly group C was predominantly attributable to periodic breathing rather than central apnea. Aminophylline produced significant improvement in periodic breathing but exerted no significant effect on the other types of apnea. Both DSI85 and DSI70 were strongly correlated (r = 0.833). CONCLUSIONS: Polygraphic study of neonates at risk revealed marked arterial oxygen desaturation, even among those with periodic breathing. This novel DSI represents a useful tool for evaluating apnea and periodic breathing in neonates and for assessing treatment efficacy.

Aminophylline↗
PubMed2005

Sphere formation and expression of neural proteins by human corneal stromal cells in vitro.

PURPOSE: To demonstrate the presence of corneal stromal precursors that express neural markers in vitro. METHODS: To isolate sphere-forming cells, human corneal stromal cells were subjected to a reaggregation-free neurosphere assay in medium containing methylcellulose gel matrix. To promote differentiation, the isolated sphere colonies were plated in wells with medium containing fetal bovine serum. Expression of nestin, vimentin, keratocan, alpha-smooth muscle actin (alphaSMA), beta-III tubulin, neurofilament M (NFM), and glial fibrillary acidic protein (GFAP) was examined in the sphere colonies and their progeny (i.e., cells migrated from sphere colonies), by immunocytochemistry and/or reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Human corneal stromal cells formed sphere colonies that had no self-renewal capability. The frequency of sphere-forming cells was 1.5% +/- 0.1% (range, 1.3%-1.6%). Most of the cells within these colonies expressed nestin and vimentin, whereas some expressed beta-III tubulin, NFM, GFAP, and alphaSMA by immunocytochemistry. Ninety-one percent and 89% of the progeny expressed vimentin and alphaSMA, respectively, whereas nestin was undetectable. beta-III tubulin-, NFM-, and GFAP-positive cells were detected in the progeny at the frequency of 7.2%, 0.9%, and 0.5%, respectively. Semiquantitative RT-PCR showed that nestin, NFM, GFAP, and keratocan gene expression was higher in the sphere colonies, whereas vimentin and alphaSMA expression increased in the progeny. CONCLUSIONS: Adult human corneal stroma contains precursor cells that express neural markers.

Adult↗
PubMed1996

Prognostic significance of abnormal p53 accumulation in primary, resected non-small-cell lung cancers.

PURPOSE: This study was conducted to evaluate the prognostic significance of p53 abnormalities in primary, resected non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Methodologic validation of immunohistologic detection of p53 abnormalities in routine pathology sections was assessed using 31 lung cancer specimens for which p53 gene status was known from our previous molecular biologic studies. Applying the optimized cutoff value, we evaluated the prognostic significance of p53 abnormalities in an independent cohort of 208 NSCLC patients with complete follow-up data, whose resections were consecutively performed between January 1984 and December 1988. RESULTS: Immunohistologic detection of p53 abnormalities appeared to be reliable and showed approximately 90% concordance with the p53 gene status. Using the selected cutoff value of 10%, 46% of 208 NSCLCs showed p53 abnormalities. There was no relationship between p53 abnormalities and clinical outcome in the entire cohort, which represented all histologic subtypes of NSCLC (P = .58). Based on the reasoning that the influence of p53 abnormalities may have been obscured by distinct biologic roles depending on histologic subtypes, we also separately analyzed subsets of patients with adenocarcinomas (n = 100) and with squamous cell carcinomas (n = 88) and found that it may be a useful prognosticator only in adenocarcinoma patients (P = .04). CONCLUSION: p53 abnormalities are not a significant prognostic factor in primary, resected NSCLC when all histologic subtypes are combined, but may be a useful prognosticator for adenocarcinomas. Additional studies are warranted for further evaluation, specifically of adenocarcinomas.

Adenocarcinoma↗