Biomedical subjects

M C Lin

Publications and source records attributed to M C Lin.

At least 55 records · Page 3Linked to original sources

PubMed2000

Novel effects of gossypol, a chemical contraceptive in man: mobilization of internal Ca(2+) and activation of external Ca(2+) entry in intact cells.

The effect of gossypol on Ca(2+) signaling in Madin Darby canine kidney (MDCK) cells was investigated by using fura-2 as a Ca(2+) probe. Gossypol evoked a rise in cytosolic free Ca(2+) levels ([Ca(2+)](i)) concentration-dependently between 2 and 20 microM. The response was decreased by external Ca(2+) removal. In Ca(2+)-free medium pretreatment with gossypol nearly abolished the [Ca(2+)](i) increase induced by carbonylcyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, and thapsigargin, an inhibitor of the endoplasmic reticulum Ca(2+) pump; but pretreatment with CCCP and thapsigargin only partly inhibited gossypol-induced Ca(2+) release. Addition of 3 mM Ca(2+) induced a [Ca(2+)](i) increase after pretreatment with 5 microM gossypol in Ca(2+)-free medium. This Ca(2+) entry was decreased by 25 microM econazole, 50 microM SKF96365 and 40 microM aristolochic acid (a phospholipase A(2) inhibitor). Pretreatment with aristolochic acid inhibited 5 microM gossypol-induced internal Ca(2+) release by 55%, but suppression of phospholipase C with 2 microM 1-(6-((17beta-3-methoxyestra-1,3, 5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione) had no effect. Gossypol (5 microM) also increased [Ca(2+)](i) in human bladder cancer cells and neutrophils. Collectively, we have found that gossypol increased [Ca(2+)](i) in MDCK cells by releasing Ca(2+) from multiple Ca(2+) stores in a manner independent of the production of inositol-1,4,5-trisphosphate, followed by Ca(2+) influx from external space.

Animals↗

PubMed2000

Mouse peroxiredoxin V is a thioredoxin peroxidase that inhibits p53-induced apoptosis.

We have identified human and mouse peroxiredoxin V (Prx-V) by virtue of the sequence homologies to yeast peroxisomal antioxidant enzyme PMP20. Prx-V represents the fifth of the six currently known subfamilies of mammalian peroxiredoxins. It is a novel organellar enzyme that has orthologs in bacteria. Biochemically, Prx-V is a thioredoxin peroxidase. One important aspect of p53 function in mammalian cells involves induction of apoptosis likely mediated by redox. We show that overexpression of Prx-V prevented the p53-dependent generation of reactive oxygen species. Likewise, Prx-V inhibited p53-induced apoptosis. Thus, Prx-V is critically involved in intracellular redox signaling.

Amino Acid Sequence↗

PubMed2000

An appraisal of liver and portal vein resection for hepatocellular carcinoma with tumor thrombi extending to portal bifurcation.

BACKGROUND: The role of surgical resection for hepatocellular carcinoma with tumor thrombi involving the major portal vein is controversial because of a high operative risk and poor prognosis. Previously, a resection was performed only when the tumor thrombi were limited to the first branch of the portal vein without extension to the portal bifurcation. HYPOTHESIS: Concomitant liver and portal vein resection may be beneficial in patients with hepatocellular carcinoma with tumor thrombi extending to portal bifurcation. DESIGN: Retrospective review. SETTING: University hospital, tertiary referral center. PATIENTS: Among 368 patients with hepatocellular carcinoma who underwent a curative resection, portal vein involvement occurred in 112 patients. Fifteen of the 112 patients underwent a concomitant liver and portal vein resection owing to extension of tumor thrombi to the portal bifurcation (group 1). The remaining 97 patients did not need portal vein resection (group 2). INTERVENTION: Surgical indications, procedures, and results of pathological examination of resected specimens were assessed in patients in group 1. The clinicopathological characteristics, operative morbidity and mortality, and operative results were compared between the 2 groups. MAIN OUTCOME MEASURES: Disease-free and actuarial survival rates. RESULTS: Intramural tumor infiltration was found at the site of thrombi adhesion to the portal vein cuff in 11 of 15 patients in group 1. Owing to patient selection bias, patients in group 1 were significantly younger and had better liver function and greater resected liver weight. The operative time, postoperative hospitalization, operative blood loss, amount of blood transfusion, and operative morbidity and mortality did not differ significantly between the 2 groups. The 5-year disease-free survival rates of groups 1 and 2 were 21.6% and 20.4% (P =.19), respectively, while the actuarial survival rates were 26. 4% and 28.5% (P =.33), respectively. CONCLUSION: Liver resection with partial resection of the portal vein is justified in selected patients with hepatocellular carcinoma with tumor thrombi extending to portal bifurcation.

Carcinoma, Hepatocellular↗

PubMed2000

Allelic imbalance in lichen sclerosus, hyperplasia, and intraepithelial neoplasia of the vulva.

BACKGROUND: Few studies have addressed in detail the genetic alterations that occur in vulvar squamous carcinomas (VSCC) and their precursor lesions. In a previous study, we determined the most common chromosomal loci for allelic imbalance (AI) in HPV-positive and -negative VSCCs. The present study was designed to determine whether AI and the microsatellite instability phenotype (MIN) were present in epithelial lesions known to be associated with VSCC. DESIGN: Fifty-seven epithelial loci were analyzed, including HPV-positive (classic) and -negative (differentiated) vulvar intraepithelial neoplasms (VINs), lichen sclerosus (LS), and nonatypical hyperplasias. Thirty-one epithelial loci (55%) were obtained from patients with associated invasive vulvar carcinoma. HPV status was determined by polymerase chain reaction analysis. AI and MIN were determined by comparisons of microdissected target tissues with stromal controls, targeting 11 chromosomal loci. RESULTS: AI was identified in all epithelial categories, involving at least one chromosomal locus in 67, 53, 50, and 43% of classic VIN, differentiated VIN, hyperplasia, and LS. MIN was infrequent (10-13%), but confined to HPV-negative epithelial changes. HPV-positive lesions generally scored for AI more frequently, but certain loci scored nearly equally in both HPV-positive and -negative lesions, including 8p, 11q, and 17p. There were no differences in frequency of AI between epithelia with and without associated invasive carcinoma. CONCLUSIONS: The presence of allelic imbalance in vulvar hyperplasia and LS supports the hypothesis that these alterations are at greater risk for neoplasia despite the absence of conspicuous cellular atypia. A model is proposed in which these changes represent monoclonal expansion and are at empirically greater risk for subsequent "critical events" leading to morphologic atypia (VIN). The possibility that these early genetic changes influence both HPV-positive and -negative pathways merits further study.

Carcinoma in Situ↗

PubMed2000

Induction of oocyte maturation by jun-N-terminal kinase (JNK) on the oncogenic ras-p21 pathway is dependent on the raf-MEK signal transduction pathway.

PURPOSE: We have previously found that microinjection of activated MEK (mitogen activated kinase kinase) and ERK (mitogen-activated protein; MAP kinase) fails to induce oocyte maturation, but that maturation, induced by oncogenic ras-p21 and insulin-activated cell ras-p21, is blocked by peptides from the ras-binding domain of raf. We also found that jun kinase (JNK), on the stress-activated protein (SAP) pathway, which is critical to the oncogenic ras-p21 signal transduction pathway, is a strong inducer of oocyte maturation. Our purpose in this study was to determine the role of the raf-MEK-MAP kinase pathway in oocyte maturation and how it interacts with JNK from the SAP pathway. METHODS: We microinjected raf dominant negative mutant mRNA (DN-raf) and the MEK-specific phosphatase, MKP-T4, either together with oncogenic p21 or c-raf mRNA, into oocytes or into oocytes incubated with insulin to determine the effects of these raf-MEK-MAP kinase pathway inhibitors. RESULTS: We found that oocyte maturation induced by both oncogenic and activated normal p21 is inhibited by both DN-raf and by MKP-T4. The latter more strongly blocks the oncogenic pathway. Also an mRNA encoding a constitutively activated MEK strongly induces oocyte maturation that is not inhibited by DN-raf or by MKP-T4. Surprisingly, we found that oocyte maturation induced by JNK is blocked both by DN-raf and MKP-T4. Furthermore, we discovered that c-raf induces oocyte maturation that is inhibited by glutathione-S-transferase (GST), which we have found to be a potent and selective inhibitor of JNK. CONCLUSION: We conclude that there is a strong reciprocal interaction between the SAP pathway involving JNK and the raf-MEK-MAP kinase pathway and that oncogenic ras-p21 can be preferentially inhibited by MEK inhibitors. The results imply that blockade of both MEK and JNK-oncogenic ras-p21 interactions may constitute selective synergistic combination chemotherapy against oncogenic ras-induced tumors.

Animals↗

PubMed2000

Resistive inspiratory muscle training: its effectiveness in patients with acute complete cervical cord injury.

OBJECTIVE: To evaluate if resistive inspiratory muscle training (RIMT) can improve lung function in patients with complete tetraplegia within half a year after trauma. DESIGN: A prospective study. The experimental patients received training with a Diemolding Healthcare Division inspiratory muscle trainer for 15 to 20 minutes per session, twice per day, 7 days a week for 6 weeks. SETTING: Hospital-based rehabilitation units. PATIENTS: Twenty patients who were in their first 6 months of complete cervical cord injury were randomly enrolled into RIMT (10 patients) and control (10 patients) groups. MAIN OUTCOME MEASURE: Spirometry, lung volume test, maximal inspiratory pressure, maximal expiratory pressure, and modified Borg scale measurements at rest were performed before training and at the end of 6 weeks of training. RESULTS: Most of the pulmonary parameters showed statistically significant improvements within the RIMT and control groups, but the improvements were greater in the RIMT group. In addition, the improvements in total lung capacity, total lung capacity predicted percentage, vital capacity, minute ventilation, forced expiratory volume in 1 second predicted percentage, and the resting Borg scale in the RIMT group showed significantly greater improvement. CONCLUSION: RIMT can improve ventilatory function, respiratory endurance, and the perceived difficulty of breathing in patients with complete cervical spinal cord injury within half a year after trauma.

Adolescent↗

PubMed2000

Influencing factors and ambulation outcome in patients with dual disabilities of hemiplegia and amputation.

OBJECTIVE: To determine the ambulatory outcome and predictive factors of successful ambulation training in patients with both hemiplegia and lower extremity amputation. DESIGN: A retrospective study. SETTING: A rehabilitation center of a university hospital. PATIENTS: Twenty-three patients with dual disabilities consecutively admitted to the rehabilitation center from 1984 to 1994. MAIN OUTCOME MEASURES: Ambulatory outcome was measured using physical therapists' and physicians' notes at discharge or the last available clinical visit. Ambulation ability was graded as community and noncommunity ambulation, which included indoor ambulation and nonambulation. Several clinical features were reviewed to assess their association with ambulation outcome. RESULTS: About two thirds of the 23 patients could be trained to be ambulatory: 10 (43.8%) achieved community ambulation and 5 (21.7%) achieved indoor ambulation. Of the clinical factors, only mental status showed a statistically significant association with good ambulation outcome (p<.05). When odds ratios were considered, several factors, including mild motor involvement, transtibial amputation, amputation before cerebrovascular accident, age younger than 60 years, and the presence of ipsilateral hemiplegia and amputation, showed trends toward association with increased ambulation achievement, although these associations were not statistically significant. CONCLUSION: Impaired mental status seemed to be the most influential negative predictive factor of achieving community ambulation. If subjects with dual disabilities are properly selected, satisfactory results of ambulation training will be obtained.

Aged↗

PubMed2000

Hypokalemic muscular paralysis causing acute respiratory failure due to rhabdomyolysis with renal tubular acidosis in a chronic glue sniffer.

CASE REPORT: A 34-year-old male was admitted to the emergency department with the development of quadriparesis and respiratory failure due to hypokalemia after prolonged glue sniffing. The patient was subsequently given mechanical ventilatory support for respiratory failure. He was weaned from the ventilator 4 days later after potassium replacement. Toluene is an aromatic hydrocarbon found in glues, cements, and solvents. It is known to be toxic to the nervous system, hematopoietic system, and causes acid-base and electrolyte disorders. Acute respiratory failure with hypokalemia and rhabdomyolysis with acute renal failure should be considered as potential events in a protracted glue sniffing.

Acidosis, Renal Tubular↗

PubMed2000

Phase II study of regimen of gemcitabine and cisplatin in advanced non-small cell lung cancer.

BACKGROUND: Cisplatin-based chemotherapy is the standard treatment for advanced non-small cell lung cancer (NSCLC). Many novel drugs, including gemcitabine, navelbine, paclitaxel and docetaxel have been used in combination with cisplatin. Of these drugs, gemcitabine is reported to have a high response rate and acceptable toxicity. The aim of this study was to evaluate the efficacy and safety of the combination of gemcitabine and cisplatin. METHODS: Thirty-two patients with NSCLC, who met the selection criteria from June 1998 to January 1999, were enrolled. All of them were confirmed by histology and were in an advanced stage, i.e. stage IIIB with pleural effusion or stage IV. Cisplatin at a dose of 80 mg/m2 was given monthly on day 15, in combination with gemcitabine at a dose of 1000 mg/m2 administered on days 1, 8 and 15 of the 28-day cycle. RESULTS: Of the 32 assessable patients, two showed complete remission and 11 achieved partial remission. The overall response was 40.6% (95% CI, 24.8-56.4%). The median time to disease progression was 7.2 months (95% CI, 4.87-9.53 months). The major hematological toxicity was neutropenia. Seven patients (22.9%) developed grade 3 and 4 neutropenia, but none developed febrile neutropenia. One patient (3.1%) had grade 3 thrombocytopenia. One patient (3.1%) developed grade 3 anemia. Nausea and vomiting were seen in 12 patients (37.5%). CONCLUSIONS: The regimen of combined gemcitabine with cisplatin is safe and effective. With this combination, a lower dose of cisplatin seems to have an efficacy similar to that in previous reports.

Adult↗

PubMed2000

Spontaneous variability of cardiac output in ventilated critically ill patients.

OBJECTIVE: To define the magnitude of spontaneous cardiac output variability over time in sedated medical intensive care unit patients attached to a continuous cardiac output monitor, and to determine whether high level positive end-expiratory pressure or inverse inspiratory-to-expiratory (I:E) ratio ventilation resulted in greater variability over time than low positive end-expiratory pressure with conventional I:E ratio ventilation. DESIGN: Prospective study. SETTING: Medical intensive care unit in a tertiary medical center. PATIENTS: A total of 22 hemodynamically stable acute respiratory failure patients with a pulmonary artery catheter inserted for hemodynamic monitoring INTERVENTIONS: After being sedated, patients were randomized ultimately to receive pressure control ventilation first at setting A (high positive end-expiratory pressure [15 cm H2O] with conventional I:E ratio [1:2]) and then at setting B (low positive end-expiratory pressure [5 cm H2O] with inverse I:E ratio [2:1]), or vice versa, and then at setting C (low positive end-expiratory pressure [5 cm H2O] with conventional I:E ratio [1:2]). Each ventilation setting period lasted 1 hr. MEASUREMENTS AND MAIN RESULTS: Cardiac output (CO) was measured continuously. The continuous CO value displayed was updated every 30-60 secs. The updated value reflected an average of the previous 3-6 mins. The coefficient of variation (CV) of CO for each setting in each patient was calculated to represent the spontaneous variability. The mean CO+/-SD and CV of each setting was 5.7+/-1.8 L/min and 4.4% for setting A, 5.6+/-1.5 L/min and 4.6% for setting B, and 5.9+/-1.7 L/min and 4.8% for setting C. Analysis of variance revealed no significant differences between the CVs of the three settings. The 95% confidence interval for the COs for each setting was approximately the mean CO+/-0.1 x mean CO measured. CONCLUSIONS: In critically ill sedated medical intensive care unit patients with stable hemodynamics, the spontaneous variability of cardiac output over time was not significant. High positive end-expiratory pressure (15 cm H2O) and inverse ratio ventilation (2:1) did not contribute to increased spontaneous variability of cardiac output.

APACHE↗

PubMed2000

Changes in endometrial PTEN expression throughout the human menstrual cycle.

Frequent mutation of the PTEN tumor suppressor gene in endometrial adenocarcinoma has led to the prediction that its product, a phosphatase that regulates the cell cycle, apoptosis, and possibly cell adhesion, is functionally active within normal endometrial tissues. We examined PTEN expression in normal human endometrium during response to changing physiological levels of steroid hormones. PTEN ribonucleic acid levels, assessed by RT-PCR, increase severalfold in secretory compared to proliferative endometrium. This suggested that progesterone, a known antineoplastic factor for endometrial adenocarcinoma, increases PTEN levels. Immunohistochemistry with an anti-PTEN monoclonal antibody displayed a complex pattern of coordinate stromal and epithelial expression. Early in the menstrual cycle under the dominant influence of estrogens, the proliferative endometrium shows ubiquitous cytoplasmic and nuclear PTEN expression. After 3-4 days of progesterone exposure, glandular epithelium of early secretory endometrium maintains cytoplasmic PTEN protein in an apical distribution offset by expanding PTEN-free basal secretory vacuoles. By the midsecretory phase, epithelial PTEN is exhausted, but increases dramatically in the cytoplasm of stromal cells undergoing decidual change. We conclude that stromal and epithelial compartments contribute to the hormone-driven changes in endometrial PTEN expression and infer that abnormal hormonal conditions may, in turn, disrupt normal patterns of PTEN expression in this tissue.

Endometrium↗

PubMed2000

Association between chlorination of drinking water and adverse pregnancy outcome in Taiwan.

Chlorination has been the major means of disinfecting drinking water in Taiwan. The use of chlorinated water has been hypothesized to lead to several adverse birth outcomes, including low birth weight and preterm delivery. We performed a study to examine the relationship between the use of chlorinated water and adverse birth outcomes in Taiwan. The study areas included 14 chlorinating municipalities (CHMs), which were defined as municipalities in which > 90% of the municipal population was served by chlorinated water, and 14 matched nonchlorinating municipalities (NCHMs), defined as municipalities in which < 5% of the municipal population is served by chlorinated water. The CHMs and NCHMs were similar to one another in terms of level of urbanization and sociodemographic characteristics. The study population comprised 18,025 women residing in the 28 municipalities who had a first parity singleton birth between 1 January 1994 and 31 December 1996 and for which complete information on maternal age, education, gestational age, birth weight, and sex of the baby were available. The results of our study suggest that there was no association between consumption of chlorinated drinking water and the risk of low birth weight.

Adult↗

PubMed2000

Sporadic microsatellite instability is specific to neoplastic and preneoplastic endometrial tissues.

Microsatellite instability is a frequent (13%-24%) finding in sporadic endometrial adenocarcinoma and its precursor lesions, but most studies are limited to patients who already have malignant or premalignant endometrial disease. We performed retrospective testing for microsatellite instability in women in whom cancers showing microsatellite instability developed later and prospective testing in randomly selected normal and anovular endometrial biopsy specimens. Microsatellite instability in cancer-bearing biopsy specimens accurately reflected that seen in matched malignant tissues obtained at hysterectomy. In 1 patient, microsatellite instability developed in a scanty sample of fragmented endometrial tissues 7 years before the onset of endometrial cancer. Prospective testing for microsatellite instability in the endometria of women unselected for subsequent appearance of endometrial cancer showed a very low rate of microsatellite instability. Only 1 endometrial specimen showing microsatellite instability was found among 75 anovulatory endometrial specimens, and none were found in 377 normal endometrial specimens and 46 polyps examined. Microsatellite instability may precede the onset of histologically diagnosed carcinoma but is rare in randomly sampled histologically normal endometrial tissues.

Carcinoma, Endometrioid↗

PubMed2000

Foot complications in people with diabetes: a community-based study in Taiwan.

BACKGROUND AND PURPOSE: This comparative cross-sectional and community-based study was aimed at defining foot complications in diabetic patients. These data have not yet been reported for Asian societies. METHODS: Of a population of 3,602 subjects aged 35 years or more in Chin-Shan, Taipei, 309 diabetic patients were identified. Two hundred and nineteen (71%) of those patients were compared to 100 individuals randomly selected for the nondiabetic control group in the same community. RESULTS: Three diabetic patients underwent lower extremity amputation and four had skin ulcerations. Diabetic patients had a significantly higher prevalence of peripheral neuropathy (32.4% vs 16%), arterial insufficiency (12.6% vs 3.0%), and medial arterial calcification (13.6% vs 5.0%), when compared to the nondiabetic controls. The age and sex-adjusted rates of hallux valgus, loss of skin hair on the dorsum of the foot, tinea unguium, arterial insufficiency, medial artery calcification, and peripheral neuropathy were significantly higher in diabetic than nondiabetic subjects. Aging and hyperglycemia (> 140 mg/dL) increased the prevalence of foot complications in both groups. Foot complications were also remarkably associated with the duration of diabetes (p = 0.003). CONCLUSIONS: This study shows that diabetes mellitus is associated with an increased likelihood of foot complications in this geographically defined Taiwanese population. Patient age and diabetic duration are associated with the significantly higher prevalence of foot complications.

Adult↗

PubMed2000

Vertical alignment axis for transtibial prostheses: a simplified alignment method.

BACKGROUND AND PURPOSE: To evaluate a simplified method of alignment for fitting a transtibial prosthesis known as the vertical alignment axis method. METHODS: We measured the relationship between the vertical projection of the prosthetic socket center (geometric center of the cross section of the transtibial prosthetic socket at the level of the patella tendon bar) and the alignment reference center (junction of the middle and posterior thirds of the longitudinal axis of the shoe) in 36 dynamically aligned transtibial prostheses. The prostheses were fabricated by students, and the fit (proper vs improper) was assessed by the faculty. RESULTS: The faculty members found 26 of the 36 prostheses to be properly fitted. The vertical projections of the socket centers of the properly-fitted prostheses were concentrated within a small area of the shoe tracing (a mean value of 1.3 mm medially and 6.4 mm anteriorly from the alignment reference center). Conversely, in the improperly-fitted prostheses, the vertical projections of the socket center were scattered well away from the alignment reference center; the mediolateral deviation was significantly greater for improperly-fitted prostheses than for those that were properly fitted (p < 0.001). CONCLUSIONS: These results demonstrate the usefulness of the vertical alignment axis procedure. This procedure may help clinicians to better understand the alignment of transtibial prostheses and gait deviations associated with improper prosthesis fit.

Adult↗

PubMed2000

The effects of one-hour wear of high-Dk soft contact lenses on corneal pH and epithelial permeability.

PURPOSE: Previous studies have shown that 1-hour closed-eye contact lens wear with a low-Dk lens causes a significant reduction in corneal pH and an increase in epithelial permeability. In the present study, we evaluated the effects of super-high-Dk/t soft lenses on corneal epithelial barrier function and stromal pH. METHODS: Corneal thickness was measured by optical pachometry, while epithelial permeability and stromal pH were measured by fluorophotometry. A paired-eye design was used in which one eye was randomly allocated to wear a high-oxygen-permeable soft lens (CIBAVision Focus/NIGHT & DAY (Dk/t= 175) while the other eye did not wear a lens. RESULTS: After 1-hour closed-eye lens wear, neither the difference in corneal swelling (P = 0.206) nor the permeability (P = 0.055) between both eyes was significantly different. The mean pH values under open-eye conditions were 7.66 vs. 7.57 for the treatment and control eyes, respectively (P = 0.082), dropping to 7.27 vs. 7.25 after 1-hour eye closure (P = 0.283). CONCLUSIONS: Although our results are limited to a 1-hour observation period, they do provide evidence that high-Dk materials may eliminate corneal acidosis and reduced epithelial barrier function that accompany closed-eye contact lens wear with lower-Dk soft lens materials.

Adolescent↗

PubMed2000

Hyperkalemic cardiac arrest successfully reversed by hemodialysis during cardiopulmonary resuscitation: case report.

Severe hyperkalemia is a potential life-threatening cardiac emergency especially in the patients who suffer from a defective renal capacity to excrete potassium such as the dialysis patient. Various conventional therapies including intravenous sodium bicarbonate, insulin with glucose and several beta-2 agonists are commonly employed as transient measures to enhance shift of potassium from the extracellular to the intracellular compartment. If the potassium load is massive and situation is critical, emergency hemodialysis may be useful. During cardiopulmonary resuscitation, the external cardiac compression can support adequate blood flow for hemodialysis. We report a case of a 68-year-old woman who developed sudden cardiac arrest secondary to hyperkalemia with renal insufficiency. Despite 100 minutes of cardiopulmonary resuscitation and conventional treatment for hyperkalemia, the cardiac arrest still persisted. Hemodialysis was then initiated during cardiopulmonary resuscitation and the patient restored spontaneous heart beat 20 minutes later. There was no neurologic sequela after her recovery. Hemodialysis should be considered early in the course of cardiopulmonary resuscitation in severe hyperkalemia induced cardiac arrest if conventional therapies were judged to be ineffective.

Aged↗

PubMed1999

Alzheimer amyloid abeta1-42 channels: effects of solvent, pH, and Congo Red.

Substantial genetic and biochemical evidence implicates amyloid peptides (Abeta) in the etiology of Alzheimer's Disease (AD). Recent evidence indicates that Abeta1-42 is the predominant species in the hallmark senile amyloid plaque of AD. Furthermore, Abeta1-42 forms aggregates inside lysosomes of cultured neurons leading to lysosomal disruption and cell death. We report here that Abeta1-42 forms slightly cation selective, voltage-independent ion channels with multiple conductance levels at neurotoxic concentrations in planar bilayer membranes. The channels show substantial irregularity of activity, and the size of conductances and the length of open lifetimes depend on solvent history. Formation of channels requires anionic lipids, is enhanced in acidic solutions, and is inhibited by Congo Red. These properties suggest that the channels are formed by aggregates of Abeta1-42. In addition, the channels are reversibly blocked by zinc in a voltage-independent manner. The properties of these channels would likely render them neurotoxic to relevant neurons in vivo. These results are consistent with the channel hypothesis of Abeta neurotoxicity.

Amyloid beta-Peptides↗