Biomedical subjects

D H Lee

Publications and source records attributed to D H Lee.

At least 109 records · Page 6Linked to original sources

PubMed2001

Sonographic findings of solid and papillary epithelial neoplasm of the pancreas.

OBJECTIVE: To evaluate the sonographic findings of solid and papillary epithelial neoplasm of the pancreas, a rare tumor occurring in young women. METHODS: The sonographic findings of 11 cases of pathologically proven solid and papillary epithelial neoplasm of the pancreas were retrospectively evaluated. RESULTS: In 6 cases (55%), combined cystic and solid portions of the masses were observed, whereas only solid-looking masses without anechoic cystic portions were seen in 4 cases (36%). One case (9%) had marginal calcification, consequently, the internal architecture was not evaluated by sonography. Internal echoes were seen in 3 of 6 cystic and solid masses. Septa were seen in 3 cases. Among 11 cases of solid and papillary epithelial neoplasm, tumor margins were well defined in 10, and tumor capsules were detected in 9 (echogenic in 7 and hypoechoic in 2). Calcifications were seen in 3 cases (27%). CONCLUSIONS: The characteristic sonographic findings of solid and papillary epithelial neoplasm were well-encapsulated, cystic, and solid masses, but sometimes the mass was seen as a pure solid-looking mass or had internal septations or calcifications.

Adult↗

PubMed2001

Expression of phospholipase C-gamma1 in experimental cholesteatoma using Mongolian gerbils.

Phospholipase C (PLC)-gamma1 is known to play a central role in ligand-mediated signal transduction for cell proliferation. The purpose of this study was to elucidate the distribution of PLC-gamma1 in deep meatal skin, retroauricular skin and cholesteatoma matrix of experimental animals. We induced canal ligation cholesteatoma using Mongolian gerbils and investigated the expression of PLC-gamma1 in this model by using Western blot analysis and immunohistochemistry. By Western blot analysis, considerably higher levels of PLC-gamma1 protein were detectable in experimental cholesteatoma. On immunohistochemistry, experimental cholesteatoma showed more intense immunolabeling of PLC-gamma1 protein than deep meatal skin and retroauricular skin. In conclusion, overexpression of PLC-gamma1 may in part contribute to abnormal proliferation and differentiation of experimental cholesteatoma in Mongolian gerbils.

Animals↗

PubMed2001

hMLH1 and hMSH2 mutations in families with familial clustering of gastric cancer and hereditary non-polyposis colorectal cancer.

The pattern of hMLHI and hMSH2 mutations was assessed to identify the genetic correlation between hereditary gastric and colorectal cancers. Four disease groups and their healthy family members were assembled according to the presentation of gastric cancer: FG, familial clustering of gastric cancer (n = 32); CG, family with one or more colorectal and gastric cancers in first-degree relatives (n = 22); HS, seven HNPCC families corresponding to the Amsterdam criteria (AMS+) and 12 suspected HNPCC families which did not satisfy one of the criteria (AMS-), but no gastric cancer among first- and second-degree relatives (n = 19); and SG, sporadic gastric cancer (n = 33). In the CG group, three were included in AMS + and six in AMS- criteria. Peripheral blood was obtained from them to detect hMLHI and hMLH2 mutations using PCR-SSCP analysis and direct sequencing. The incidence of mutations was 9.4% in the FG group, 54.5% in the CG group, 31.6% in the HS group, and none in the SG group. The incidence, type, and number of the mutation were not different between the CG and HS groups. Thirty-four different mutations included 19 in hMLH1 and 15 in hMSH2. Gastric cancer was the most common extracolonic malignancy in HNPCC and suspected HNPCC families (9/28, 32.1%). The hMLH1 or hMSH2 mutation occurred in seven of 10 families with AMS+, whereas it occurred in four of 18 with AMS- (70% vs. 22.2%, P = .013). Five mutations in the hMLH1 and six mutations in the hMSH2 were exclusively found in families with gastric cancer. All three mutations in the FG group were in hMLHI and there was no mutation in their healthy family members. This study demonstrates that some familial clustering type of gastric cancer appears to be associated with hMLHI mutations thereby indicating a difference from the hereditary gastric cancer studies previously reported. In addition, hMLHI and hMSH2 mutations may impact the gastric cancer carcinogenesis in HNPCC or suspected HNPCC.

Adaptor Proteins, Signal Transducing↗

PubMed2001

Blood partition and protein binding of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378.

The blood partition of KR-31378 between plasma and blood cells and the factors influencing the binding of the drug to 4% human serum albumin (HSA) using an equilibrium dialysis technique were evaluated. KR-31378 reached an equilibrium rapidly between plasma and blood cells of rabbit blood. The equilibrium plasma/blood cells concentration ratios were independent of initial rabbit blood concentrations of KR-31378, 1, 10 and 50 microg/ml; the values were in the range of 1.42-2.33. It took approximately 12-h incubation to reach an equilibrium between plasma and isotonic Søresen phosphate buffer of pH 7.4 containing 3% dextran ('the buffer'). The binding of KR-31378 to 4% HSA was dependent on HSA concentrations (the binding values were 25.3 and 32.0% for HSA concentrations of 2 and 5%, respectively), incubation temperature (the binding values were 48.8, 29.0 and 25.8% for 4, 22 and 37 degrees C, respectively), pHs of isotonic Sørensen phosphate buffer containing 3% dextran (the binding values were 17.7, 20.6, 22.8, 25.6 and 29.5% for buffer pHs of 5.8, 6.4, 7.0, 7.4 and 8.0, respectively) and alpha-1-acid glycoprotein (AAG) concentrations (the binding values were 25.6, 29.9, 34.4 and 50.3% for AAG concentrations of 0, 0.08, 0.16 and 0.32%, respectively).

Animals↗

PubMed2000

o-raffinose cross-linked hemoglobin improves the hemostatic defect associated with anemia and thrombocytopenia in rabbits.

Several different preparations of cross-linked hemoglobin (CLHb) are being evaluated for their efficacy and safety as red cell substitutes in a variety of preclinical and clinical settings. Because CLHb is known to sequester nitric oxide (NO) and inhibit NO-mediated processes, we hypothesized that CLHb would have a hemostatic effect by enhancing platelet reactivity, inducing vasoconstriction, or both. Infusion of o-raffinose CLHb shortened the prolonged microvascular bleeding time and decreased blood loss from ear incisions in rabbits rendered anemic and thrombocytopenic. Moreover, this hemostatic effect persisted for at least 24 hours after infusion. Phenylephrine induced a degree of vasoconstriction similar to that induced by CLHb but did not shorten the bleeding time or decrease blood loss, suggesting that vasoconstriction alone cannot account for the hemostatic effect of CLHb. There was no evidence of CLHb-induced activation of coagulation in vivo, since infusion of CLHb did not increase circulating levels of thrombin-antithrombin complex. In vitro, CLHb abolished the inhibitory effect of the NO donor 3-morpholinosydnonimine on platelet aggregation and enhanced the aggregation of stimulated but not resting platelets. This potentiating effect was not attenuated by the addition of superoxide dismutase or catalase. To evaluate the potential arterial thrombogenicity of CLHb, a model of carotid artery thrombosis was developed in rabbits without thrombocytopenia or anemia. Compared with albumin infusion, CLHb infusion shortened the time to complete carotid occlusion. These data suggest that CLHb may shift the thromboregulatory balance toward clot formation, resulting in decreased bleeding in anemic and thrombocytopenic rabbits and possibly increasing arterial thrombogenicity in normal rabbits.

Adrenergic alpha-Agonists↗

PubMed2000

Molecular characteristics of the inhibition of human neutrophil elastase by nonsteroidal antiinflammatory drugs.

Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandin synthesis. Human neutrophil elastase (HNElastase; HNE, EC 3.4.21.37) has been known as a causative factor in inflammatory diseases. To investigate the specific relationship between HNElastase inhibition and specificity of molecular structure of several NSAIDs, HNElastase was purified by Ultrogel AcA54 gel filtration, CM-Sephadex ion exchange, and HPLC (with TSK 250 column) chromatography. HNElastase was inhibited by aspirin and salicylate in a competitive manner and by naproxen, ketoprofen, phenylbutazone, and oxyphenbutazone in a partial competative manner, but not by ibuprofen and tolmetin. HNElastase-phenylbutazone-complex showed strong Raman shifts at 200, 440, 1124, 1194, 1384, 1506, and 1768 cm(-1). The Raman bands 1194, 1384, and 1768 cm(-1) may represent evidences of the conformational change at -N=N-phi radical, pyrazol ring, and -C=O radical of the elastase-drug complex, respectively. Phenylbutazone might be bound to HNElastase by ionic and hydrophobic interaction, and masked the active site. Inhibition of HNElastase could be another mechanism of action of NSAIDs besides cyclooxygenase inhibition in the treatment of inflammatory diseases. Different inhibition characteristics of HNE-lastase by NSAIDs such as aspirin, phenylbutazone-like drugs and ineffective drugs could be important points for drawing the criteria for appropriate drugs in clinical application.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2000

Applicability of carcinoembryonic antigen-specific monoclonal antibodies to radioimmunoguided surgery for human colorectal carcinoma.

Two carcinoembryonic antigen (CEA)-specific monoclonal antibodies (MAbs), PR1A3 and T84.66, were tested to determine whether they could accurately localize colorectal carcinoma and therefore be applicable in radioimmunoguided surgery (RIGS). Twenty-one tumors by three human colorectal carcinoma cell lines with various levels of CEA expression (KM-12c, C75, and Clone A) were successfully implanted in the intra-abdominal organs of 15 nude mice. The tumors was localized using a portable radioisotope detector (Neoprobe 1000) 48 h after injection of radiolabeled MAbs (10 mCi/mouse) when the precordial counts were <20 per 2 s. Histopathological identification of radiolabeled MAbs were also performed using immunohistochemistry and microautoradiography. Radioactivity counted on a portable radioisotope detector correlated well with that on a gamma counter. The distribution in the blood was significantly greater than in other organs (P < 0.001). Localization indices of the tumor in various organs was from 1.1 to 8.5 in the PR1A3-pretreated mice and 3.0 to 8.6 in the T84.66-pretreated mice. Silver grains and immune staining were distributed in the tumor cells of the PR1A3-pretreated mice, whereas they were in the necrotic debris as well as the tumor cells of the T84.66-pretreated mice. There were significantly more silver grains in the liver in the T84.66-pretreated mice than in the PR1A3-pretreated mice (P = 0.004). The sensitivity and specificity of tumor localization by RIGS were 71.4 and 91.4% in the PR1A3-pretreated mice, whereas they were 60 and 76% in the T84.66-pretreated mice. A study using specific anti-CEA MAbs suggested PR1A3 as an efficient immune probe for RIGS in colorectal carcinoma with a low rate of false-positive detection.

Animals↗

PubMed2000

Expression of bone morphogenetic protein receptors type-IA, -IB and -II correlates with tumor grade in human prostate cancer tissues.

Bone morphogenetic proteins (BMPs) are potential regulators of prostate cancer cell growth and metastasis that signal through an interaction with BMP membrane receptors (BMPRs) type I and type II. In the present study, Western blot and immunohistochemical analysis of BMPRs were carried out in benign and malignant human prostate tissues to explain the loss of BMP response in human prostate cancer cells. The results demonstrated that the benign prostate specimens expressed high levels of all three BMPRs. In normal prostate, BMPRs were localized predominantly to epithelial cells. Among prostate cancer specimens, well-differentiated cancers were positive for the expression of BMPR-II, BMPR-IA, and BMPR-IB, for the most part. In contrast, only 1 of 10 poorly differentiated prostate cancer cases was positive for each of the three BMPRs (P < 0.005 for all three receptors). Taken together, these results indicate that human prostate cancer cells frequently exhibit loss of expression of BMPRs and suggest that loss of BMPRs may play an important role during the progression of prostate cancer.

Blotting, Western↗

PubMed2000

beta-Amyloid(1-42) binds to alpha7 nicotinic acetylcholine receptor with high affinity. Implications for Alzheimer's disease pathology.

Alzheimer's disease pathology is characterized by the presence of neuritic plaques and the loss of cholinergic neurons in the brain. The underlying mechanisms leading to these events are unclear, but the 42-amino acid beta-amyloid peptide (Abeta(1-42)) is involved. Immunohistochemical studies on human sporadic Alzheimer's disease brains demonstrate that Abeta(1-42) and a neuronal pentameric cation channel, the alpha7 nicotinic acetylcholine receptor (alpha7nAChR), are both present in neuritic plaques and co-localize in individual cortical neurons. Using human brain tissues and cells that overexpress either alpha7nAChR or amyloid precursor protein as the starting material, Abeta(1-42) and alpha7nAChR can be co-immunoprecipitated by the respective specific antibodies, suggesting that they are tightly associated. The formation of the alpha7nAChR.Abeta(1-42) complex can be efficiently suppressed by Abeta(12-28), implying that this Abeta sequence region contains the binding epitope. Receptor binding experiments show that Abeta(1-42) and alpha7nAChR bind with high affinity, and this interaction can be inhibited by alpha7nAChR ligands. Human neuroblastoma cells overexpressing alpha7nAChR are readily killed by Abeta(1-42), whereas alpha7nAChR agonists such as nicotine and epibatidine offered protection. Because Abeta(1-42) inhibits alpha7nAChR-dependent calcium activation and acetylcholine release, two processes critically involved in memory and cognitive functions, and the distribution of alpha7nAChR correlates with neuritic plaques in Alzheimer's disease brains, we propose that interaction of the alpha7nAChR and Abeta(1-42) is a pivotal mechanism involved in the pathophysiology of Alzheimer's disease.

Acetylcholine↗

PubMed2000

Mucosa-specific targets for regulation of IFN-gamma expression: lamina propria T cells use different cis-elements than peripheral blood T cells to regulate transactivation of IFN-gamma expression.

Activation of lamina propria (LP) T cells via the CD2 pathway enhances IFN-gamma (IFN-gamma) secretion with further enhancement after CD28 coligation. The molecular mechanisms regulating IFN-gamma expression in LP T cells remain unknown. Previous studies in PBL and T cell lines identified cis- and trans-regulatory elements in TCR-mediated expression of IFN-gamma. This study examines CD2 and PMA/ionophore-responsive IFN-gamma promoter elements. Activation of LPMC via CD2-induced IFN-gamma secretion and a parallel up-regulation of mRNA expression. CD28 coligation enhanced mRNA stability without up-regulating transcription as measured by nuclear run-on. Transfection of a -2.7-kb IFN-gamma promoter-reporter construct into PBL and LP mononuclear cells (LPMC) revealed significant promoter activity after CD2 activation, with additional transactivation after CD2/CD28 costimulation in PBL, but not in LPMC. Functional analysis using truncated promoter fragments identified distinct cis-regulatory regions selectively transactivating IFN-gamma expression in PBL compared with LPMC. In PBL, CD2 activation elements reside within the -108- to +64-bp region. However, in LPMC the upstream region between -204 and -108 bp was essential. Transfection of the proximal and distal AP-1-binding elements, as well as TRE/AP-1 constructs, revealed functional activation of AP-1 subsequent to CD2 signaling, with activation critical in PBL but diminished in LPMC. Electromobility shift analysis using oligonucleotides encompassing the proximal, distal, and BED/AP-1-binding regions failed to demonstrate selective transactivation after CD2 signaling of LPMC. This report provides evidence that activation of LPMC results in transactivation of multiple promoter elements regulating IFN-gamma expression distinct from those in PBL.

5' Untranslated Regions↗

PubMed2000

Dose-dependent pharmacokinetics of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378, in rats.

The dose-dependent pharmacokinetic parameters of a new neuroprotective agent for ischemia-reperfusion damage, KR-31378, were evaluated after intravenous and oral administration, 10, 20, and 50 mg/kg, to rats. After intravenous administration of 50 mg/kg, the dose-normalized (10 mg/kg) AUC (994 microg min/mL) was significantly greater than that at 10 (569 microg min/ml) and 20 (660 microg min/mL) mg/kg. This could be due to slower clearance (Cl) with increasing dosage (18.5, 14.6, and 10.2 mL/min/kg for 10, 20, and 50 mg/kg, respectively). The slower Cl with increasing dosage could be due to saturable metabolism of KR-31378 in rats and this could be supported by significantly slower Cl(nr) and significantly greater 24-h urinary excretion of the drug at 50 mg/kg than those at 10 and 20 mg/kg. After oral administration of 50 mg/kg, the dose-normalized (10 mg/kg) AUC (1160 microg min/mL) was significantly greater than that at 10 (572 microg min/mL) and 20 (786 microg min/mL) mg/kg. Note that the AUCs were comparable (not significantly different) between intravenous and oral administration at each dosage, indicating that the absorption from gastrointestinal tract was almost complete and the first-pass (gastric, intestinal, and hepatic) effect was not considerable after oral administration to rats.

Analysis of Variance↗

PubMed2000

Transanally injected triamcinolone acetonide in levator syndrome.

PURPOSE: Several treatments are used for the treatment of levator syndrome, such as rectal massage, biofeedback, and galvanic stimulation. But their effects are inconsistent, and multiple treatment sessions are usually required. Triamcinolone acetonide and lidocaine mixture was injected locally into the tenderest point in levator syndrome under the hypothesis that levator syndrome is caused by tendinitis of pelvic floor musculature. METHODS: A mixture of 40 mg of triamcinolone acetonide and 1 ml of 2 percent lidocaine was injected into the tenderest point transanally in 104 patients (33 males; mean age, 51 years) with levator syndrome from December 1996 to May 1998 at Daehang Clinic. Additional injections were repeated at two-week intervals to a maximum of three injections in cases of poor response. Follow-up was performed prospectively concerning patient's perception of pain level using a visual analog scale. Depending on the response, the patients were classified into four groups: pain-free, good, fair, and no response. More than 50 percent pain reduction was classified as "good," and less than 49 percent reduction as "fair." RESULTS: The injection regions, where the tenderest points were identified on digital rectal compression, were left anterior anal canal in 71.2 percent of patients, right anterior in 3.8 percent of patients, and posterior in 25 percent of patients. The results of treatment were as follows: at three months after injection, response was classified as pain-free in 36.8 percent of patients, good in 35 percent of patients, fair in 19.5 percent of patients, and no response in 8.7 percent of patients; at six months the response was pain-free in 30.1 percent of patients, good in 46.5 percent of patients, fair in 18.2 percent of patients, and no response in 5.2 percent of patients. Most patients, except 8.7 percent at three months and 5.2 percent at six months, experienced treatment benefits. There were no complications during the follow-up periods. CONCLUSION: Transanal injection of triamcinolone acetonide and lidocaine mixture into the tenderest point is such a simple, safe, and very effective modality that it can be recommended as a primary therapy for levator syndrome.

Adolescent↗

PubMed2000

Frequency data on four tetrameric STR loci D18S1270, D14S608, D16S3253 and D21S1437 in a Korean population.

We present the results of a population study in Korea for four new tetrameric short tandem repeat (STR) loci employing multiplex PCR amplification, polyacrylamide gel electrophoresis of the PCR products and silver staining, which allow single base pair resolution and rapid typing. The loci tested were D18S1270, D14S608, D16S3253 and D21S1437 and all loci showed no significant deviations from Hardy-Weinberg equilibrium in more than 100 unrelated Koreans. This allelic frequency data can be used in forensic analyses and paternity tests to estimate the frequency of a multiplex PCR based DNA profile in the Korean population.

Base Sequence↗

PubMed2000

Changes of glucose transporters in the cerebral adaptation to hypoglycemia.

Repeated hypoglycemia increases the glycemic thresholds of responses of counterregulatory hormones and of symptoms to subsequent hypoglycemia. This may in part be due to cerebral adaptation to hypoglycemia, which involves glucose transporter-1 (GLUT1) and glucose transporter-3 (GLUT3). To investigate the role of brain GLUT1 and GLUT3 in cerebral adaptation to chronic hypoglycemia, GLUT1 and GLUT3 mRNA and protein expressions were determined in rat brain using RT-PCR and Western blot analyses after 4- and 8-day hypoglycemic insults. Hypoglycemia was induced in rats by twice daily subcutaneous injection of intermediate-acting insulin with dosage adjustment according to the blood glucose levels. Target level of hypoglycemia (< 2.5 mmol/l) was achieved at least once a day in all rats included. Control rats received saline injections. Blood glucose levels during the 4 and 8 days of insulin treatment were 2.18 +/- 0.12 and 2.68 +/- 0.07 mmol/l, respectively. Following the 4 and 8 days of hypoglycemia, GLUT1 mRNA levels did not significantly change. GLUT3 mRNA expressions after the 4 days of hypoglycemia increased by 36.9 +/- 9.4% compared with that in control rats (P = 0.031), but after the 8 days of hypoglycemia, did not change. On Western blot analysis of total particulate rat brain membrane, amount of 55-kDa isoform of GLUT1 protein did not change after 4- and 8-day hypoglycemia (88.1 +/- 4.9% of control, P = 0.240; 92.1 +/- 1.4% of control, P = 0.096, respectively). In contrast, the expression of GLUT3 protein in the 4-day hypoglycemic rats increased by 51.4 +/- 8.4% compared with that in control rats (P = 0.004). After the 8 days of hypoglycemia, the expression also tended to increase by 44.9 +/- 14.4% (P = 0.119). There was an inverse correlation between the amount of GLUT3 protein expression and mean blood glucose levels in 4-day hypoglycemic and control rats (r = -0.886, P = 0.019). These data suggest that GLUT3 isoform plays a role in the cerebral adaptation to chronic hypoglycemia.

Adaptation, Physiological↗

PubMed2000

Characteristics of ectopic discharges in a rat neuropathic pain model.

Injured afferent neurons produce spontaneous activity that is generated away from the normal impulse generation site. Since this activity, referred to as ectopic discharges, may play a significant role in neuropathic pain, it is important to systematically analyze the activity in various pain states. The present study used the segmental spinal nerve injury model of neuropathic pain to quantify the ectopic discharges from injured afferents in the neuropathic rat under various conditions. All aspects of measured ectopic discharges declined as postoperative time lengthened. Neuropathic pain behaviors declined in a similar fashion over the same time period. Surgical sympathectomy on neuropathic animals lowered the level of ectopic discharges along with neuropathic pain behaviors. The data indicate that the level of ectopic discharges is well correlated with that of pain behaviors in a rat neuropathic pain model, and this reinforces the supposition that ectopic discharges are important to the maintenance of neuropathic pain behaviors. The data suggest that there are two components of ectopic discharge generator mechanisms: sympathetically dependent and sympathetically independent components.

Action Potentials↗

PubMed2000

2,3-Dihydro-dithiin and -dithiepine-1,1,4,4-tetroxides: small molecule non-peptide antagonists of the human galanin hGAL-1 receptor.

The neuropeptide galanin modulates several physiological functions such as cognition, learning, feeding behavior, and depression, probably via the galanin 1 receptor (GAL-R1). Using an HTS assay based on 125I-human galanin binding to the human galanin-1 receptor (hGAL-R1), we discovered a series of 1,4-dithiin and dithiipine-1,1,4,4-tetroxides that exhibited binding affinity IC50's to hGAL-R1 ranging from 190 to 2700 nM. Two of the dithiepin analogues, 7 and 23, behaved pharmacologically as hGAL-R1 antagonists in secondary assays involving adenylate cyclase activity and GTP binding to G-proteins. Analogues 7 and 23 were also active in functional assays involving galanin, reversing the inhibitory effect of galanin on acetylcholine (ACh) release in rat brain hippocampal slices and electrically-stimulated guinea pig ileum twitch.

Acetylcholine↗

PubMed2000

MRI techniques: bilateral findings and "normal findings".

Magnetic resonance imaging (MRI) techniques allow for significantly better imaging of the temporal lobe compared to computed tomography (CT) or other non-invasive modalities. For detection of foreign tissue lesions, MRI surpasses CT. For the highest non-invasive yield for detection of mesial temporal sclerosis, optimal sequences that should be employed are a heavily T1-weighted volumetric acquisition (to enable both volumetric calculation of hippocampal volume, and, if needed, intracranial volume), T2-weighted coronal sequences, with or without T2-mapping, fluid-attenuated inversion recovery (FLAIR) and, to exclude subtle susceptibility effects from hematoma or cavernoma, gradient echo scans. Magnetic resonance spectroscopy (MRS) may show a decrease in N-acetyl aspartate (NAA) concentration, or NAA: Choline + creatine ratio. Functional MRI is a new and exciting tool that offers the promise of accurately localizing hemispheric functions; its role in the preoperative evaluation of temporal lobe seizures remains uncertain at present.

Hippocampus↗

PubMed2000

Amyloid peptide Abeta(1-42) binds selectively and with picomolar affinity to alpha7 nicotinic acetylcholine receptors.

We have recently reported evidence that a very high affinity interaction between the beta-amyloid peptide Abeta(1-42) and the alpha7 nicotinic acetylcholine receptor (alpha7nAChR) may be a precipitating event in the formation of amyloid plaques in Alzheimer's disease. In the present study, the kinetics for the binding of Abeta(1-42) to alpha7nAChR and alpha4beta2nAChR were determined using the subtype-selective nicotinic receptor ligands [(3)H]methyllycaconitine and [(3)H]cytisine. Synaptic membranes prepared from rat and guinea pig cerebral cortex and hippocampus were used as the source of receptors. Abeta(1-42) bound to the alpha7nAChR with exceptionally high affinity, as indicated by K(i) values of 4.1 and 5.0 pM for rat and guinea pig receptors, respectively. When compared with the alpha7nAChR, the affinity of Abeta(1-42) for the alpha4beta2nAChR was approximately 5,000-fold lower, as indicated by corresponding K(i) values of 30 and 23nM. The results of this study support the concept that an exceptionally high affinity interaction between Abeta(1-42) and alpha7nAChR could serve as a precipitating factor in the formation of amyloid plaques and thereby contribute to the selective degeneration of cholinergic neurons that originate in the basal forebrain and project to the cortex and hippocampus.

Aconitine↗