Biomedical subjects

C Y Hsu

Publications and source records attributed to C Y Hsu.

At least 91 records · Page 5Linked to original sources

PubMed1999

Differential effect of cycloheximide on neuronal and glioma cells treated with chemotherapy and radiation.

Dividing cells and non-dividing cells are distinct in their cell cycle kinetics, and react differently when facing cytotoxic stimuli. A protein synthesis inhibitor, cycloheximide (CHX), has recently been found to protect neuronal cells from oxidative stress. We investigated whether CHX exerts differential effects on dividing and non-dividing cells in the brain under cytotoxic stimuli. Mitotic C6 rat glioma cells and postmitotic neuronal cells were studied with a cytotoxic regimen combining gamma-irradiation (RT) and 1,3-bis,2-chloroethyl-1-nitrosourea (BCNU). Cells were exposed to BCNU (1 g/ml) for 15 h before gamma-irradiation and incubated with CHX (1 g/ml) from 30 min before and until 5 h after irradiation. Clonogenic assay was used to assess cytotoxic effects on C6 glioma cells. LDH assay was used for the viability of H19-7 postmitotic neuronal cells. A 2.27-3.75 fold enhancement of cytotoxicity was noticed with the addition of CHX to BCNU and 2-10 Gy of radiation. Our data demonstrated that CHX enhanced cytotoxicity of RT plus BCNU, while no additional toxicity was incurred to the postmitotic neuronal cells when CHX was added. We further studied whether the inhibition of DNA repair, assayed by single-cell DNA electrophoresis (comet assay), is a contributing factor for the enhanced cytotoxicity on C6 glioma cells. Interestingly, the initial DNA damage after RT plus BCNU was equivalent; whereas DNA repair was significantly less at 5 h after radiation in CHX-treated C6 glioma cells. Protecting non-dividing neuronal cells to avoid excessive functional deficit is an integral part of a successful brain tumor treatment regimen. Taking advantage of the differential effect of CHX on glioma and neuronal cells may improve tumor control without excessive neural toxicity.

Animals↗

PubMed1999

Pyrrolidine dithiocarbamate induces bovine cerebral endothelial cell death by increasing the intracellular zinc level.

The antioxidant and metal-chelating effects of pyrrolidine dithiocarbamate (PDTC) have been extensively studied. PDTC prevents cell death induced by various insults. However, PDTC itself may cause cell death in selected experimental paradigms. PDTC induced bovine cerebral endothelial cell death. However, in serum-depleted medium, PDTC did not affect the cell viability, suggesting that certain factors in serum may mediate the cytotoxic effect of PDTC. The metal chelators bathocuproine disulfonic acid, o-phenanthroline, bathophenanthroline disulfonic acid, and N,N,N',N'-tetrakis(2-pyridyl-methyl)ethylenediamine (TPEN) prevented the cell death induced by PDTC. In a serum-deprived condition, addition of exogenous metals, copper or zinc, restored the cytotoxic effect of PDTC. These data indicate that metals such as copper or zinc in serum may mediate the cytotoxic effect of PDTC. The potency of zinc for PDTC-induced endothelial cell death was greater than that of copper. Zn-EDTA did not block PDTC-induced cell death, whereas Ca-EDTA and Cu-EDTA were able to prevent this PDTC effect. PDTC increased the intracellular fluorescence of the zinc probe dye N-(6-methoxy-8-quinolyl)-p-toluenesulfonamide, which was quenched by TPEN or various EDTA preparations but not by Zn-EDTA. Results suggest that an increase in intracellular zinc concentration is required in PDTC-induced cerebral endothelial cell death.

Animals↗

PubMed1999

Quantitative magnetic resonance imaging in experimental hypercapnia: improvement in the relation between changes in brain R2 and the oxygen saturation of venous blood after correction for changes in cerebral blood volume.

Acute hypercapnia simultaneously induces increases in regional cerebral blood volume (rCBV) and the oxygen saturation of cerebral venous blood (Yv). Changes in both physiologic parameters may influence the changes in R2 (deltaR2) that can be measured in the brain with gradient echo magnetic resonance imaging. The authors examined the effect of incorporating independent measurements of the change in rCBV (deltarCBV) on the fidelity of the relation between deltaR2 and deltaYv in the setting of experimental hypercapnia. A two-dimensional T2-weighted gradient echo sequence was used to measure deltaR2 in the brain parenchyma of anesthetized rats in response to hypercapnia with respect to the control state. In parallel, estimates of rCBV were obtained using a three-dimensional steady-state approach in conjunction with a paramagnetic contrast agent during both control and hypercapnic states so that a deltarCBV could be calculated. Regional CBV values of 2.96 +/- 0.82% and 5.74 +/- 1.21% were obtained during the control and hypercapnic states, respectively, and linear relations between rCBV and CO2 tension in both arterial (r = 0.80) and jugular venous (r = 0.76) blood samples were obtained. When correlating deltaR2 directly with deltaYv, no clear relation was apparent, but a strong linear relation (r = 0.76) was observed when correction for deltarCBV was incorporated into the data analysis. These results are consistent with the current understanding of the mechanisms of blood oxygen level-dependent (BOLD) contrast and underscore the potential importance of taking into account deltarCBV when quantitative estimates of deltaYv from the "BOLD effect" are intended.

Animals↗

PubMed1999

Predictors of acute hospital costs for treatment of ischemic stroke in an academic center.

BACKGROUND AND PURPOSE: We sought to determine predictors of acute hospital costs in patients presenting with acute ischemic stroke to an academic center using a stroke management team to coordinate care. METHODS: Demographic and clinical data were prospectively collected on 191 patients consecutively admitted with acute ischemic stroke. Patients were classified by insurance status, premorbid modified Rankin scale, stroke location, stroke severity (National Institutes of Health Stroke Scale score), and presence of comorbidities. Detailed hospital charge data were converted to cost by application of department-specific cost-to-charge ratios. Physician's fees were not included. A stepwise multiple regression analysis was computed to determine the predictors of total hospital cost. RESULTS: Median length of stay was 6 days (range, 1 to 63 days), and mortality was 3%. Median hospital cost per discharge was $4408 (range, $1199 to $59 799). Fifty percent of costs were for room charges, 19% for stroke evaluation, 21% for medical management, and 7% for acute rehabilitation therapies. Sixteen percent were admitted to an intensive care unit. Length of stay accounted for 43% of the variance in total cost. Other independent predictors of cost included stroke severity, heparin treatment, atrial fibrillation, male sex, ischemic cardiac disease, and premorbid functional status. CONCLUSIONS: We conclude that the major predictors of acute hospital costs of stroke in this environment are length of stay, stroke severity, cardiac disease, male sex, and use of heparin. Room charges accounted for the majority of costs, and attempts to reduce the cost of stroke evaluation would be of marginal value. Efforts to reduce acute costs should be monitored for potential cost shifting or a negative impact on quality of care.

Academic Medical Centers↗

PubMed1999

Renal cell carcinoma: unusual pediatric renal tumors.

Renal cell carcinoma (RCC), the most common renal tumor in adults, is rare in childhood, with an incidence much lower than that of Wilms' tumor. It is initially asymptomatic, but clinically overt symptoms such as an abdominal mass or hematuria may indicate late-stage disease and a poor prognosis. In this report, we describe the imaging features of pediatric RCC and emphasize the value of early diagnosis offered by ultrasonographic screening. From 1989 through 1997, we encountered five children (aged 7-15 yr) with RCC. Of these, two presented with symptoms, while the other three were asymptomatic and were identified in a large, school-based urologic ultrasonographic survey, in which more than 800,000 children were screened by our team. Reviewing the imaging features, we found that four tumors exhibited a heterogeneous nature. One patient had bilateral well-defined homogeneous tumors, which proved to be bilateral low-grade RCC. The three asymptomatic patients had smaller tumors than the other two patients. These three were treated with nephrectomy and were well after at least 15 months of follow-up. The two patients who presented with symptoms eventually died of tumor recurrence and pulmonary metastasis, respectively. The findings in these five cases of pediatric RCC add knowledge regarding the imaging features of this disease and highlight the value of ultrasonographic screening for early diagnosis.

Adolescent↗

PubMed1999

Tuberculous meningitis in a Filipino maid.

Tuberculous meningitis, while not uncommon in Taiwan, has not been reported among foreign workers. We report the first case of tuberculous meningitis in a 37-year-old Filipino maid in Taiwan, who presented with headache, fever and vomiting. She had been well before this episode and the small screening films of the chest radiograph obtained on her arrival in Taiwan 15 months previously, and every 6 months thereafter showed no evidence of tuberculosis. The suspicion of tuberculous meningitis was delayed until disturbance of consciousness manifested and a standard chest radiograph showed a diffuse miliary pattern in both lung fields. A cerebrospinal fluid sample that was sent for a polymerase chain reaction-based assay specific for Mycobacterium tuberculosis showed a positive result. The patient recovered with sequelae of mildly incoherent speech and urinary incontinence after antituberculous medication and short-course steroid treatment. Clinicians should be aware of the possibility of tuberculous meningitis in foreign workers with complaints of fever and headache. Because high-quality chest radiographs are a prerequisite for early detection of pulmonary tuberculosis, we recommended that standard posterior-anterior chest radiographs should be obtained as part of the routine health examination for foreign workers.

Aged↗

PubMed1998

Sensitive determination of a new antiarrhythmic agent, trecetilide, in plasma by high-performance liquid chromatography with fluorescence detection.

Two high-performance liquid chromatography (HPLC) methods were developed for the determination of trecetilide in plasma samples. Differing only in the addition of a derivatization step and different detection wavelengths, the two methods encompassed a wide concentration range. In both methods, plasma samples (0.1 ml) with added internal standard were applied to solid-phase extraction discs containing a non-polar/strong cation mixed-phase, washed and eluted with an acetone-acetonitrile triethylamine mixture. The eluate was evaporated to dryness, and either reconstituted and directly injected onto an HPLC column or first derivatized with 1-naphthyl isocyanate before HPLC analysis. In both methods, the separation was performed isocratically on a cyano analytical column utilizing a mobile phase composed of acetonitrile-pH 7.9 phosphate buffer (70:30, v/v). The column effluent was monitored by fluorescence detection at 290/345 nm (with derivatization) or 235/320 nm (without derivatization). The limits of detection and quantitation of the assay were 0.57 and 1.9 ng/ml, respectively, when derivatization was used, or 4.3 and 14 ng/ml, respectively, without derivatization.

Anti-Arrhythmia Agents↗

PubMed1998

Amyloid beta-peptide possesses a transforming growth factor-beta activity.

Amyloid beta-peptide (Abeta) of 39-42 amino acid residues is a major constituent of Alzheimer's disease neurite plaques. Abeta aggregates (fibrils) are believed to be responsible for neuronal damage and dysfunction, as well as microglia and astrocyte activation in disease lesions by multiple mechanisms. Since Abeta aggregates possess the multiple valencies of an FAED motif (20th to 23rd amino acid residues), which resembles the putative transforming growth factor-beta (TGF-beta) active site motif, we hypothesize that Abeta monomers and Abeta aggregates may function as TGF-beta antagonists and partial agonists, analogous to previously described monovalent and multivalent TGF-beta peptide antagonists and agonists (Huang, S. S., Liu, Q., Johnson, F. E., Konish, Y., and Huang, J. S. (1997) J. Biol. Chem. 272, 27155-27159). Here, we report that the Abeta monomer, Abeta-(1-40) and its fragment, containing the motif inhibit radiolabeled TGF-beta binding to cell-surface TGF-beta receptors in mink lung epithelial cells (Mv1Lu cells). Abeta-(1-40)-bovine serum albumin conjugate (Abeta-(1-40)-BSA), a multivalent synthetic analogue of Abeta aggregates, exhibited cytotoxicity toward bovine cerebral endothelial cells and rat post-mitotic differentiated hippocampal neuronal cells (H19-7 cells) and inhibitory activities of radiolabeled TGF-beta binding to TGF-beta receptors and TGF-beta-induced plasminogen activator inhibitor-1 expression, that were approximately 100-670 times more potent than those of Abeta-(1-40) monomers. At less than micromolar concentrations, Abeta-(1-40)-BSA but not Abeta-(1-40) monomers inhibited proliferation of Mv1Lu cells. Since TGF-beta is an organizer of responses to neurodegeneration and is also found in neurite plaques, the TGF-beta antagonist and partial agonist activities of Abeta monomers and aggregates may play an important role in the pathogenesis of the disease.

Amino Acid Sequence↗

PubMed1998

Methylprednisolone inhibition of TNF-alpha expression and NF-kB activation after spinal cord injury in rats.

Post-traumatic inflammatory reaction has been implicated in the secondary injury after SCI. TNF-alpha is a key inflammatory mediator, which plays a pathogenetic role in cell death in inflammatory disorders and traumatic brain injury. TNF-alpha exerts its effector actions, at least partially, through the activation of a pro-inflammatory transcription factor, NF-kB, which in turn upregulates such genes as iNOS, cytokines, adhesive molecules, and others. Consistent with a post-traumatic inflammatory reaction after SCI, we noted an increase in TNF-alpha expression by Western blotting (4.5-fold increase at 1 day after SCI, P<0.01) and immunohistochemistry in a rat SCI model. Post-traumatic TNF-alpha expression was accompanied by an increase in NF-kB binding activity in nuclear proteins isolated from the injured cord (3.9-fold increase, P<0.01). MP is the only drug proven effective in improving neurological function in patients with acute SCI. The mechanism of action of MP is not fully understood, but is thought to be related to its antioxidant effects. MP is also a potent anti-inflammatory agent, which has been recently shown to inhibit NF-kB binding activity. MP (30 mg/kg, i.v.) given immediately after SCI reduced TNF-alpha expression by 55% (P<0.01) and NF-kB binding activity. These findings suggest that post-traumatic inflammatory activity that is mediated by the TNF-alpha-NF-kB cascade can be suppressed by MP.

Animals↗

PubMed1998

Outpatient weekly chemotherapy in patients with nasopharyngeal carcinoma and distant metastasis.

BACKGROUND: Distant metastasis is a more common pattern of failure than locoregional recurrence after adequate radiotherapy in patients with nasopharyngeal carcinoma (NPC). The objective of this Phase II study was to assess the efficacy and toxicity of weekly chemotherapy in NPC patients with distant metastasis. METHODS: Patients with a histologic diagnosis of NPC and documented distant metastasis were eligible, including those who 1) had metastatic disease at presentation; 2) had developed metastatic disease during or at any time after local radiotherapy; or 3) had developed progressive disease or recurrence of metastasis after prior chemotherapy. The weekly chemotherapy regimen was comprised of 5-fluorouracil (5-FU), 1250 mg/m2, plus cisplatin, 25 mg/m2, as a 24-hour continuous intravenous infusion via a subcutaneous implanted port, using an ambulatory pump in an outpatient setting for the first 19 patients. Because of the low incidence and reduced severity of toxicity, the dosage of chemotherapy was escalated to 5-FU, 1667 mg/m2, plus cisplatin, 33.3 mg/m2, for the subsequent 25 patients. RESULTS: Between October 1992 and June 1996, a total of 44 patients with metastatic NPC were studied. They were 36 males and 8 females with a median age of 48 years (range, 30-72 years). Poorly differentiated epidermoid carcinoma or undifferentiated carcinoma were the major pathologic types. Twenty-six patients had single organ metastasis, whereas 18 patients had multiple organ involvement. Locoregional disease existed simultaneously in 16 patients. The majority of patients had received previous radiotherapy (33 patients) and chemotherapy (23 patients: 16 as concurrent therapy for localized disease, 6 as salvage therapy for metastatic disease, and 1 for a postradiation adjuvant purpose). Among 38 patients with measurable disease, 8 obtained a complete response (CR) (21.1%), 12 obtained a partial response (PR) (31.6%), 17 had stable disease (SD) (44.7%), and 1 had progressive disease (2.6%). The median duration of CR, PR, and SD were 6.5 months, (range, 2-12 months), 5.5 months (range, 2-9 months), and 2.5 months (range, 1-6 months), respectively. Toxicity was found to be very mild. Only one patient developed a World Health Organization (WHO) Grade 1 mucositis. No visible alopecia and no treatment-related deaths occurred. WHO Grade 3-4 hematologic toxicities occurred in 1.0% of patients for leukopenia, 4.1% for anemia, and 2.9% for thrombocytopenia. CONCLUSIONS: Data from the current study indicate that 24-hour weekly infusion of 5-FU plus cisplatin has moderate activity but very low toxicity for NPC patients with distant metastasis. Further study is necessary to find more effective therapy.

Adult↗

PubMed1998

Involvement of de novo ceramide biosynthesis in tumor necrosis factor-alpha/cycloheximide-induced cerebral endothelial cell death.

Cytokines, including tumor necrosis factor-alpha (TNF-alpha), may elicit cytotoxic response through the sphingomyelin-ceramide signal transduction pathway by activation of sphingomyelinases and the subsequent release of ceramide: the universal lipid second messenger. Treatment of bovine cerebral endothelial cells (BCECs) with TNF-alpha for 16 h followed by cycloheximide (CHX) for 6 h resulted in an increase in ceramide accumulation, DNA fragmentation, and cell death. Application of a cell permeable ceramide analogue C2 ceramide, but not the biologically inactive C2 dihydroceramide, also induced DNA laddering and BCEC death in a concentration- and time-dependent manner. TNF-alpha/CHX-mediated ceramide production apparently is not a result of sphingomyelin hydrolysis because sphingomyelin content does not decrease in this death paradigm. In addition, an acidic sphingomyelinase inhibitor, desipramine, had no effect on TNF-alpha/CHX-induced cell death. However, addition of fumonisin B1, a selective ceramide synthase inhibitor, attenuated TNF-alpha/CHX-induced intracellular ceramide elevation and BCEC death. Together, these findings suggest that ceramide plays at least a partial role in this paradigm of BCEC death. Our results show, for the first time, that ceramide derived from de novo synthesis is an alternative mechanism to sphingomyelin hydrolysis in the BCEC death process initiated by TNF-alpha/CHX.

Animals↗

PubMed1998

MIB-1 labeling index in nonpilocytic astrocytoma of childhood: a study of 101 cases.

BACKGROUND: The prognosis of pediatric patients with nonpilocytic astrocytoma, and in particular those with anaplastic astrocytoma, is somewhat unpredictable. This study used MIB-1 monoclonal antibody, a proliferative marker that can be used in formalin fixed paraffin embedded tissues, to study nonpilocytic pediatric astrocytoma. METHODS: Astrocytoma, anaplastic astrocytoma, and glioblastoma specimens excised from a total of 101 pediatric patients during the period from January 1975 to September 1996 were retrieved from the authors' surgical pathology file. Histologic grading of the specimens was performed based on a modified Ringertz system. The proliferative potential of the tumors was estimated by using the MIB-1 labeling index (LI), which was evaluated with morphologic grades of tumors and survival of the patients. RESULTS: Of the 101 patients, 34 had astrocytoma, 33 had anaplastic astrocytoma, and 34 had glioblastoma. Their mean survival times were 165.2+/-14.9 months (mean+/-standard error; SE), 46.1+/-9.9 months, and 21.8+/-5.6 months, respectively. The mean MIB-1 LI of different tumor grades were as follows: astrocytoma, 3.9+/-4.3 (mean+/-standard deviation; range, 0.0-21.6); anaplastic astrocytoma, 24.3+/-15.6 (range, 1.7-62.8); and glioblastoma, 35.9+/-16.4 (range, 7.36-63.3). The mean survival of the entire group of patients with LIs < or = 11 was 173.2+/-12.2 months (mean+/-SE), and the mean survival of those with LIs > 11 was 20.3+/-4.1 months. The survival of anaplastic astrocytoma patients with LIs < or = 11 was similar to that of astrocytoma patients, whereas the survival of anaplastic astrocytoma patients with LI > 11 was similar to that of patients with glioblastoma. CONCLUSIONS: The results of the current study show that histopathologic grading can predict the outcome for patients with astrocytomas and glioblastomas, whereas MIB-1 LI can separate better and worse prognostic groups in patients with anaplastic astrocytoma.

Adolescent↗

PubMed1998

Upregulation of pleiotrophin gene expression in developing microvasculature, macrophages, and astrocytes after acute ischemic brain injury.

Pleiotrophin (PTN) is a heparin-binding, 18 kDa secretory protein that functions to induce mitogenesis, angiogenesis, differentiation, and transformation in vitro. PTN gene (Ptn) expression is highly regulated during development and is highest at sites in which mitogenesis, angiogenesis, and differentiation are active. In striking contrast, with the exception of the neuron, the Ptn gene is only minimally expressed in adults. We now demonstrate that Ptn gene expression is strikingly upregulated within 3 d in OX42-positive macrophages, astrocytes, and endothelial cells in areas of developing neovasculature after focal cerebral ischemia in adult rat. Ptn gene expression remains upregulated in these same cells and sites 7 and 14 d after ischemic injury. However, expression of the Ptn gene is significantly decreased in cortical neurons 6 and 24 hr after injury and is undetectable in degenerating neurons at day 3. Neurons in contralateral cortex continue to express Ptn in levels equal to control, uninjured brain. It is suggested that PTN may have a vital role in neovascular formation in postischemic brain and that postischemic brain is an important model in which to analyze sequential gene expression in developing neovasculature. In contrast, Ptn gene expression in injured neurons destined not to recover is strikingly reduced, and potentially its absence may contribute to the failure of the neuron to survive.

Acute Disease↗

PubMed1998

Down-regulation of nucleophosmin/B23 during retinoic acid-induced differentiation of human promyelocytic leukemia HL-60 cells.

Human promyelocytic leukemia HL-60 cells were induced to undergo granulocytic differentiation by treatment with retinoic acid (RA, 10 microM, 1-5 days). The steady-state level of nucleophosmin/B23 mRNA decreased during the RA-induced differentiation. There was also decrease in the level of total cellular nucleophosmin/B23 protein during the RA-induced differentiation. Stabilization and nuclear run-on assays indicate that the decrease in nucleophosmin/B23 mRNA in RA-treated HL-60 cells was transcriptionally regulated. Unlike c-myc mRNA, there was virtually no decline of nucleophosmin/B23 mRNA during the growth arrest by serum-starvation. The decrease in nucleophosmin/B23 mRNA expression in HL-60 cells subsequent to retinoic acid treatment can thus be attributed to cellular differentiation rather than the growth arrest induced by RA. Nucleophosmin/B23 antisense oligomer treatment significantly potentiated RA-induced cellular differentiation. Results of this study suggest that nucleophosmin/B23 is one of the key elements in the down-regulation of nucleolar function for cellular differentiation.

Cell Differentiation↗

PubMed1998

The diazoxide derivative IDRA 21 enhances ischemic hippocampal neuron injury.

The diazoxide derivative IDRA 21 and other positive modulators of (AMPA)-type glutamate receptors are considered potential memory-enhancing agents. However, AMPA receptor activation contributes to CA1 hippocampal neuron damage from global ischemia in rodents, raising the possibility that 7-chloro-3-methyl-3-4-dihydro-2H-1,2,4 benzothiadiazine S,S-dioxide (IDRA 21) or drugs with similar actions may worsen ischemic neuronal injury. Here we demonstrate that glutamate plus IDRA 21 kills cultured rat hippocampal neurons by AMPA receptor activation, and, in vivo, 12 and 24 mg/kg of IDRA 21 given orally increases CA1 neuron loss produced by 10 minutes of global ischemia. Treating patients with drugs that potentiate AMPA receptor activation will have to consider these potential effects, particularly when coexistent with conditions in which excessive activation of AMPA receptors may occur (eg, stroke, seizures).

Animals↗

PubMed1998

Experimental hypoxemic hypoxia: changes in R2* of brain parenchyma accurately reflect the combined effects of changes in arterial and cerebral venous oxygen saturation.

A two-dimensional T2*-weighted gradient-echo sequence was used to image the rat brain before and during graded hypoxemia. Changes in R2* (deltaR2*) with respect to the control state were calculated for brain parenchyma and were compared with changes in hemoglobin saturation measured from both arterial and jugular venous blood samples. DeltaR2* was first correlated with the changes in arterial (deltaYa) and venous (deltaYv) hemoglobin saturations individually. Although a general trend toward a linear relationship with deltaR2* was observed for both deltaYa and deltaYv, neither alone was strong (correlation coefficients r=0.71 and 0.75 for deltaYa and deltaYv, respectively, and standard errors of the regression (SER)=0.52 and 0.48 for deltaYa and deltaYv, respectively). However, when an "effective" cerebral blood hemoglobin saturation change (deltaYb) was constructed that takes into account the approximate weighting of the contributions from the arterial and venous phases of the circulation (deltaYb = 0.75 x deltaYv + 0.25 x deltaYa), a stronger correlation with deltaR2* was obtained and there was less variance (r=0.87 and SER=0.35). It is concluded that an appropriate weighting of the contributions of arterial and venous phases of the circulation must be taken into account in modeling the volume susceptibility effects of deoxyhemoglobin on R2* of brain parenchyma. In this way, a more accurate relationship between deltaR2* and deltaYb can be obtained.

Analysis of Variance↗

PubMed1998

Effects of acute normovolemic hemodilution on T2*-weighted images of rat brain.

Acute normovolemic hemodilution (HD) was induced in anesthetized rats to assess the effect of changes in hematocrit (Hct) on signal intensity in T2*-weighted magnetic resonance (MR) images. Other relevant physiological parameters were maintained invariant. Two degrees of HD were induced: mild (Hct reduced from 42.6+/-2.2% to 33.4+/-2.1%) and moderate (Hct reduced from 44.6+/-2.7% to 26.2+/-1.7%). A two-dimensional gradient-echo sequence was used to monitor signal changes with high temporal resolution before, during, and after HD protocols. The time course of signal intensity change was closely related to that of changes in Hct. Corresponding changes in R2* (deltaR2*) with respect to the pre-HD state were calculated for the brain parenchyma. Average deltaR2* values of -0.24+/-0.06 s(-1) and -0.40+/-0.07 s(-1) were obtained for the mild and moderate HD groups, respectively, during the final 2 min of MR imaging (proximal to correlative measurements of Hct). MR measured deltaR2* values were in close agreement with the expected changes in R2* predicted from theory when the measured changes in Hct were used as independent variables. These data are in good agreement with the current understanding of the effects of changes in the intravascular concentration of deoxyhemoglobin on induced magnetic susceptibility and hold promise for quantitative measurement of brain oxygenation in vivo.

Analysis of Variance↗

PubMed1998

Effect of acetic acid on telomerase activity in cervical intraepithelial neoplasia.

OBJECTIVE: To evaluate whether the telomerase activity in CIN lesions can be affected by a chemical solution of acetic acid, which is required to apply to the cervix prior to colposcopy-directed biopsy. MATERIALS AND METHODS: Thirty-five patients with histologically confirmed high-grade squamous intraepithelial lesions of the cervix entered the study. Two specimens were collected from each patient, one before and one after the cervix was swabbed with 5% acetic acid. The standard telomeric repeat assay protocol (TRAP) was used to examine telomerase activity in these fresh frozen tissue samples. Normal cervical tissues from 10 control individuals were also examined for the presence of telomerase activity. A total of 80 specimens was analyzed. RESULTS: Telomerase activity was detectable in 27 of 35 (77.1%) fresh tissue samples, 15 of 35 (42.9%) tissue samples swabbed with 5% acetic acid, and 0 of 10 (0%) normal cervical tissue samples, respectively. Twelve samples became telomerase negative after 5% acetic acid applied. Among the 15 telomerase-positive tissue samples swabbed with 5% acetic acid, 12 had relative weak telomerase activity compared to corresponding fresh tissue samples, the other 3 remained the same. Therefore, it is concluded that telomerase activity was affected by 5% acetic acid in 24 of 27 (88.9%) samples. Telomerase activity in HeLa cell line was also inhibited by 5% acetic acid. CONCLUSION: We reported a relative high percentage of telomerase expression in high-grade CIN lesions when compared with previous reports. If detection of telomerase activity is to become a tool for diagnosis and prognosis of cervical neoplasias, applying acetic acid prior to colposcopy-directed biopsy that is submitted for telomerase assay should be avoided in order to increase the detection rate.

Acetic Acid↗