Measurement of psychological state changes at low dopamine transporter occupancy following a clinical dose of mazindol.

RATIONALE: The beneficial effects of psychostimulant drugs in the treatment of psychiatric disorders occur because they increase the extracellular dopamine concentration by inhibiting re-uptake of extracellular dopamine at dopamine transporters. However, the psychological effects at low dopamine transporter occupancy have not been well demonstrated. OBJECTIVES: The purpose of the study was to evaluate the psychological effects, dopamine transporter occupancy, and dopamine release induced by a single oral administration of a clinical dose of mazindol. METHODS: Ten healthy male volunteers were orally administered a placebo and a clinical dose of mazindol (1.5 mg) on separate days. The psychological effects of mazindol were assessed using a visual analogue scale to detect alterations in the state of consciousness. The amount of blockade of dopamine transporters was assessed using positron emission tomography with [18F]FE-PE2I and extracellular dopamine release was measured as the amount of change in [11C]raclopride binding. RESULTS: Following administration of a clinical dose of mazindol, the dopamine transporters were blocked by 24-25 %, and the binding potential of [11C]raclopride was reduced by 2.8-4.6 %. The differences of a score measuring derealisation and depersonalization associated with a positive basic mood were significantly correlated with the change in the [11C]raclopride binding in the limbic striatum. CONCLUSIONS: A subtle alteration in the state of consciousness was detected with a correlation to the changes in the [11C]raclopride binding, which implies that a subtle alteration in extracellular dopamine concentration in the limbic striatum by a small amount of dopamine transporter occupancy can affect the state of consciousness. TRIAL REGISTRATION HTTPS://UPLOAD.UMIN.AC.JP/CGI-OPEN-BIN/CTR_E/CTR_VIEW.CGI?RECPTNO=R000009703 : UMIN000008232.

Effectiveness of a simulated patient training programme based on trainee response accuracy and appropriateness of feedback.

INTRODUCTION: Simulated patients (SPs) need education and training in required skills to be effective resources in education. This study was conducted to examine the effectiveness of an SP training programme based on the accuracy of trainee responses and the appropriateness of their feedback. METHODS: Thirty-two applicants to the training programme and 35 experienced SPs were included in this study. The experienced SPs served as a reference group. The rate of accurate responses and the rate of appropriate feedback were assessed with pre- and post-training tests, and these two outcome measures were compared with those of the experienced SPs. RESULTS: No significant differences were found in trainee response accuracy or appropriateness of feedback between pre- and post-training tests. The response accuracy rate of the trainees on the pre-training test was significantly lower than that of SPs with 1-2 years of experience, whilst there was no significant difference between these SPs and the trainees on the post-training test. CONCLUSIONS: Although our study suggests that more training is needed to improve the skills of SPs, the training programme may contribute to helping trainees reach a novice level in the skill of providing accurate responses. SP training should be encouraged to contribute to the effectiveness of such teaching and to establish the validity of the assessment.

[Complete resection of Pancoast tumor following induction chemoradiotherapy improves survival].

OBJECTIVE: Pancoast tumors are some of the most challenging thoracic malignant diseases to treat because of their proximity to vital structures at the thoracic inlet. We retrospectively analyzed 23 patients with pT3-4, N0-3 Pancoast tumors who underwent combined chest wall resection including the 1st rib, and discuss the anatomical considerations, assessment of induction therapy, and surgical approaches for these cancers. METHODS: Between 1983 and 2006, 23 patients with Pancoast tumors underwent combined resection of the 1st rib at our institute. Of those, 21 were male and 2 were female, with an average age of 58 years. There were 10 each of squamous cell carcinoma and adenocarcinoma, 2 large cell carcinoma, and 1 adenosquamous carcinoma. Over the past decade, induction chemoradiotherapy (>40Gy) was employed before surgery. RESULTS: A posterior approach was employed in 14 patients, an anterior approach in 7, and a combined anterior and posterior approach in 2. Sixteen patients underwent complete resection. One of 7 patients undergoing incomplete resection (4.3%) died on the 45th postoperative day. The 3- and 5-year survival rates were 50 and 22%, respectively, for patients with complete resection. No case survived for more than 8 months out of the 7 patients with incomplete resection. Fourteen patients with pN0 showed significantly better survival than those with pN1-3 (p = 0.0053). CONCLUSION: Recent literature and our results suggest that patients with pN0 and/or a pathological complete response (pCR) after induction chemoradiotherapy could achieve long-term survival after complete resection.

[Surgical treatment for the second double lung cancers following chemotherapy for small cell lung cancer].

We report a case with surgery for the 2nd primary double lung cancers-adenocarcinoma and squamous cell carcinoma which developed in the right upper lobe after 5 years successful control by chemotherapy for small cell lung cancer in the left upper lobe. Long term survivors with small cell lung cancer have recently increased as a result of progress of chemotherapy. Therefore, 2nd primary lung cancer is not rare after the treatment for the initial small cell lung cancer. Although several causes have been proposed on the development of 2nd primary lung cancer after small cell lung cancer treatment, smoking history was strongly suggested as a cause in this case. Careful follow-up especially focusing on 2nd primary lung cancer development is necessary for patients after successful treatment for small cell lung cancer.

Molecular characterization of the E gene of dengue virus type 1 isolated in Guangdong province, China, in 2006.

We determined the genetic relationships and origin of the dengue virus (DENV) responsible for an outbreak of dengue fever (DF) in Guangdong province, China, in 2006. Five DENV type 1 (DENV-1) isolates were obtained from human serum samples collected from DF patients during the outbreak. The nucleotide sequences of the E (envelope) gene were compared with those of 48 previous DENV-1 isolates: 18 from Guangdong province, one from Fujian province, one from Zhejiang province, and 28 from other countries in the South Asian region. The results suggested that four DENV-1 isolates identified in Guangdong province in 2006 might be in general circulation there, although these DENV-1 viruses may have been originally introduced into the province from other countries. In contrast, one isolate from Guangzhou city in 2006, may have been introduced by a recently imported case from Cambodia.

Proteomic analysis of stage I primary lung adenocarcinoma aimed at individualisation of postoperative therapy.

Although postoperative adjuvant chemotherapy (PAC) with uracil-tegafur significantly improves the prognosis of patients with stage I lung adenocarcinoma, subset analysis has revealed that only 11.5% of patients with stage IB derive actual benefit from such therapy. Therefore, it is extremely important to identify patients for whom adjuvant chemotherapy will be beneficial. We performed comprehensive protein analysis of 24 surgically resected specimens of stage I adenocarcinoma using liquid chromatography-tandem mass spectrometry (LC-MS/MS), followed by bioinformatical investigations to identify protein molecules. Furthermore, we carried out immunohistochemical studies of 90 adenocarcinoma specimens to validate the results of LC-MS/MS. We detected two kinds of protein molecules (myosin IIA and vimentin) by LC-MS/MS. We confirmed their immunohistochemical expression and distribution, and evaluated the relationship between the expression of these proteins and prognosis after adjuvant chemotherapy. Patients with no expression of either myosin IIA or vimentin showed a significantly better outcome regardless of PAC using uracil-tegafur. However, we were unable to select responders to uracil-tegafur using these proteins. Cases of adenocarcinoma lacking expression of either myosin IIA or vimentin show a good outcome without PAC, and therefore do not require such treatment.

Changes in the autoimmune blistering response: a clinical and immunopathological shift from pemphigus foliaceus to bullous pemphigoid.

We describe a 64-year-old Brazilian man who developed bullous pemphigoid (BP) 12 years after pemphigus foliaceus (PF) was diagnosed. On his first presentation in 1992, histological examination revealed intraepidermal blistering and acantholysis at the granular layer, direct immunofluorescence (DIF) demonstrated intercellular deposits of C3 in the epidermis, and indirect immunofluorescence showed the presence of IgG antibodies against the intercellular spaces. In 2004, laboratory findings revealed a subepidermal blister with neutrophils and eosinophils (by histology), DIF demonstrated deposition of IgG and C3 along the basement membrane zone, salt-split skin showed IgG deposition in the epidermal side of the blister, and immunoblotting showed reactivity against BP180. The occurrence of two autoimmune blistering conditions in the same patient is a rare event, and may suggest an intermolecular epitope-spreading phenomenon.

Social information-processing skills training to promote social competence and prevent aggressive behavior in the third grades.

This article describes a school-based study designed to promote social competence and reduce aggressive behavior by strengthening children's skills in processing social information and regulating emotions. Three successive cohorts of 3rd graders (N = 548) from 2 schools participated. In 2000-2001, children received a routine health curriculum; in 2001-2002, students received the Making Choices: Social Problem Solving Skills for Children (MC) program; and in 2002-2003, children received MC supplemented with teacher and parent activities. Compared with children in the routine condition, children in both MC conditions were rated lower on posttest social and overt aggression and higher on social competence. Moreover, they scored significantly higher on an information-processing skills posttest. The findings suggest that prevention programs can strengthen social- emotional skills and produce changes in aggressive behavior.

Comparación de la prevalencia de la infección del estómago por el Helicobacter pylori en el Perú en población japonesa y peruana / Comparison of the prevalence of Helicobacter pylori stomach infection in Peruvian and Japanese population

Se ha planteado la posibilidad de una predisposición racial para adquirir la infección del estómago por el Helicobacter pylori. Sin embargo, no se ha tenido en cuenta el nivel socioeconómico de los pacientes. Objetivo: Comparar la prevalencia de la infección por Helicobacter pylori en la población japonesa residente en el Perú y en peruanos nativos, con similares condiciones socioeconómicas. Material y métodos: Estudio prospectivo realizado en el Policlínico Peruano-Japonés (Lima-Perú), donde incluimos a dos grupos de pacientes: japoneses y peruanos nativos con síntomas crónicos del tracto gastrointestinal superior, ambos de nivel socioeconómico medio y alto. Se excluyeron pacientes con úlcera péptica. Para diagnosticar la infección se utilizó la prueba de la ureasa, la Reacción en Cadena de la Polimerasa (PCR) y serología con ELISA IgG. Resultados: Evaluamos 168 pacientes de raza japonesa (edad promedio 54.6±12.62 años, 75% mujeres), y los comparamos con 161 peruanos (edad 42.12±14.48 años, 61.5% mujeres). Utilizando la prueba de la ureasa, la prevalencia de infección por el Helicobacter pylori en peruanos fue de 47.8% y en japoneses de 47.0% (p=0.88). Utilizando PCR, en peruanos fue de 49.7% y en japoneses 43.5% (p=0.28). Conclusiones: En el Perú, las personas de raza y ascendencia japonesa pura comparados con población peruana del mismo estrato social y similar grupo etáreo, tienen similar prevalencia de la infección por el Helicobacter pylori, con lo que podemos postular que en el Perú y en estos grupos étnicos no existe predisposición racial para adquirir la infección.

Objective: To compare the prevalence of Helicobacter pylori infection in native Peruvians and Japaneses residing in Peru. METHODS: Prospective study carried out at [quot ]Policlinico Peruano-Japonés[quot ] (Lima-Perú). We included Peruvians and Japaneses residing in Peru with chronic symptoms of the upper gastrointestinal tract. Both groups were from medium to high socioeconomic status. We excluded patients with peptic ulcer. PCR, rapid ureasa test and IgG ELISA were used to diagnose the infection. RESULTS: We evaluated 168 Japaneses (mean age 54.6 +/- 12.62 years, 75% female), and 161 Peruvians (mean age of 42.12 +/- 14.48 years, 61.5% female). Using the rapid ureasa test, the prevalence of Helicobacter pylori infection in Peruvians was 47.8%, and in Japaneses 47.0% (p=0.88). Using PCR, in Peruvians was 49.7% and in Japaneses 43.5% (p=0.28). CONCLUSION: Peruvians and Japaneses residing in Peru have a similar prevalence of Helicobacter pylori infection, after controlling factors such as socioeconomic status and age, suggesting that in Peru and in these ethnic groups, there is no racial predisposition to acquire the infection.

Comparación de la prevalencia de la infección del estómago por el Helicobacter pylori en el Perú en población japonesa y peruana / Comparison of the prevalence of Helicobacter pylori stomach infection in Peruvian and Japanese population

Se ha planteado la posibilidad de una predisposición racial para adquirir la infección del estómago por el Helicobacter pylori. Sin embargo, no se ha tenido en cuenta el nivel socioeconómico de los pacientes. Objetivo: Comparar la prevalencia de la infección por Helicobacter pylori en la población japonesa residente en el Perú y en peruanos nativos, con similares condiciones socioeconómicas. Material y métodos: Estudio prospectivo realizado en el Policlínico Peruano-Japonés (Lima-Perú), donde incluimos a dos grupos de pacientes: japoneses y peruanos nativos con síntomas crónicos del tracto gastrointestinal superior, ambos de nivel socioeconómico medio y alto. Se excluyeron pacientes con úlcera péptica. Para diagnosticar la infección se utilizó la prueba de la ureasa, la Reacción en Cadena de la Polimerasa (PCR) y serología con ELISA IgG. Resultados: Evaluamos 168 pacientes de raza japonesa (edad promedio 54.6±12.62 años, 75% mujeres), y los comparamos con 161 peruanos (edad 42.12±14.48 años, 61.5% mujeres). Utilizando la prueba de la ureasa, la prevalencia de infección por el Helicobacter pylori en peruanos fue de 47.8% y en japoneses de 47.0% (p=0.88). Utilizando PCR, en peruanos fue de 49.7% y en japoneses 43.5% (p=0.28). Conclusiones: En el Perú, las personas de raza y ascendencia japonesa pura comparados con población peruana del mismo estrato social y similar grupo etáreo, tienen similar prevalencia de la infección por el Helicobacter pylori, con lo que podemos postular que en el Perú y en estos grupos étnicos no existe predisposición racial para adquirir la infección.(AU)

Objective: To compare the prevalence of Helicobacter pylori infection in native Peruvians and Japaneses residing in Peru. METHODS: Prospective study carried out at [quot ]Policlinico Peruano-Japonés[quot ] (Lima-Perú). We included Peruvians and Japaneses residing in Peru with chronic symptoms of the upper gastrointestinal tract. Both groups were from medium to high socioeconomic status. We excluded patients with peptic ulcer. PCR, rapid ureasa test and IgG ELISA were used to diagnose the infection. RESULTS: We evaluated 168 Japaneses (mean age 54.6 +/- 12.62 years, 75% female), and 161 Peruvians (mean age of 42.12 +/- 14.48 years, 61.5% female). Using the rapid ureasa test, the prevalence of Helicobacter pylori infection in Peruvians was 47.8%, and in Japaneses 47.0% (p=0.88). Using PCR, in Peruvians was 49.7% and in Japaneses 43.5% (p=0.28). CONCLUSION: Peruvians and Japaneses residing in Peru have a similar prevalence of Helicobacter pylori infection, after controlling factors such as socioeconomic status and age, suggesting that in Peru and in these ethnic groups, there is no racial predisposition to acquire the infection.(AU)

Development of innovative group work practice using the intervention research paradigm.

Rothman and Thomas' intervention research (IR) paradigm provides an alternative, developmental research method that is appropriate for practice research, especially at the early stages. It is more flexible than conventional experimental designs, capitalizes on the availability of small samples, accommodates the dynamism and variation in practice conditions and diverse populations, and explicitly values practitioners' insights. This article describes two studies to exemplify how the features of IR methodology are well suited to research on innovative group interventions. In one study, a face-to-face psychoeducational group for patients living with sickle cell anemia and chronic depression was used. The other study used an online job stress support group for social workers. The challenges and opportunities that can arise when applying the IR paradigm to develop new interventions are also discussed.

Nicotine withdrawal induces subsensitivity of hypothalamic-pituitary-adrenal axis to stress in rats: implications for precipitation of depression during smoking cessation.

Epidemiologic studies show that smokers with a past history of depression are more likely to relapse into depression after smoking cessation than those without a history of depression. These studies suggest the existence of a direct biological link between nicotine withdrawal and depression. To investigate the neuronal and hormonal mechanisms of the precipitation of depression during smoking cessation, we used an animal model of nicotine withdrawal and studied the function of the hypothalamic-pituitary-adrenal (HPA) axis, the abnormality of which is implicated in the pathogenesis of depression. Rats were implanted with a minipump delivering nicotine at 6.0 mg/kg/day for 12 days. The minipumps were removed in order to abruptly terminate nicotine infusion. The activity of the HPA axis was determined on day 2 of withdrawal using the stress-induced corticosterone response and the dexamethasone suppression test (DST). At the same time the expressions of glucocorticoid receptor (GR) mRNA in the hippocampus and paraventricular nucleus of hypothalamus (PVN) and corticotropin-releasing hormone (CRH) mRNA in PVN were determined by non-radioactive in situ hybridization. Nicotine withdrawal resulted in lower corticosterone levels during restraint stress, suggesting subsensitivity of the HPA axis to stress. The result of DST, however, did not show a significant difference between nicotine-withdrawal and control rats. These effects of nicotine withdrawal were not accompanied by any changes in the expressions of GR and CRH mRNA in either hippocampus or PVN. These results suggest that subsensitivity of the HPA axis to stress during nicotine withdrawal may be implicated in the precipitation of depression during smoking cessation, although GR and CRH in the HPA axis do not appear to play a significant role.

Bronchomalacia associated with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries, and chromosome 22q11.2 deletion.

Respiratory distress is one of the major complications in young infants with pulmonary atresia, ventricular septal defect and major aortopulmonary collateral arteries (PA-VSD-MAPCA); however, its aetiology remains obscure. We have previously reported an association of bronchomalacia with PA-VSD-MAPCA in patients with a hemizygous deletion of chromosome 22q11.2 (del.22q11). To clarify the clinical relevance of bronchomalacia in patients with PA-VSD-MAPCA and del.22q11, we reviewed the clinical and laboratory records of four patients with PA-VSD-MAPCA who had del.22q11 and bronchomalacia. External bronchial compression by anomalous patterning of the aorta and MAPCA was documented in three of the four patients, using combinatorial examination of angiocardiography, bronchography, fibreoptic bronchoscopy and magnetic resonance imaging. One of the four patients died suddenly of severe respiratory distress at 4 years of age, while the remaining three were inoperable for complete surgical repair. Our study indicates that bronchomalacia as a result of external vascular compression may be an aetiology of early-onset respiratory distress in some patients with PA-VSD-MAPCA and del.22q11, and can significantly affect the clinical outcome.

Palladium-catalyzed sulfinylzincation: 1-alkynyl sulfoxides as a sulfinyl anion equivalent.

[reaction--see text] Novel Pd-catalyzed sulfinylzincation of activated alkynes was developed, wherein 1-alkynyl sulfoxides work as a sulfinylating agent. Transfer of the sulfinyl group proceeded in a highly syn-selective fashion, giving a beta-sulfinyl vinylzinc species. Using 3,3-dimethyl-1-butynyl p-tolyl sulfoxide as a sulfinyl source, heterocoupling with propiolate derivatives was also accomplished.

Increased incidence of colorectal adenomas in follow-up evaluation of patients with newly diagnosed hyperplastic polyps.

BACKGROUND: Although adenomatous polyps have been established clearly as precursor lesions for most cases of colorectal cancer, the role, if any, of hyperplastic polyps remains uncertain. The aim of the current study was to determine whether a patient with an index finding of hyperplastic polyp on colonoscopy is at increased risk for adenomatous polyps. METHODS: We conducted a retrospective cohort study using the records of a single surgeon's colonoscopic experience over a 20-year period (June 1973 to December 1994). Patients found to have hyperplastic lesions on index colonoscopy were compared with those who had "clean" index colonoscopies. The two groups were compared for the subsequent diagnosis of adenomatous polyps on follow-up colonoscopies. Those with cancer or adenomas at index colonoscopy or in their history were excluded. We used Cox proportional hazard modeling with subsequent adenoma or cancer diagnosis at follow-up colonoscopy as the outcome, controlling for age and gender. RESULTS: We identified 42 patients for whom hyperplastic polyps were the only colorectal neoplasms found on the index examination, in contrast to 362 control patients who had a "clean" index examination. In this cohort study, patients found to have only hyperplastic polyps on initial examination had a rate of subsequent adenoma diagnoses (42%) twice that of patients with a clean initial colonoscopy (21%). Mean follow-up time was 4.3 years. The relative rate ratio was 2.0 (95% confidence interval, 1.2-3.4). CONCLUSIONS: This study suggests that patients found to have hyperplastic polyps on initial colonoscopic examination may have twice the risk of adenomas on follow-up colonoscopy, as compared with those who have clean initial examinations. If this finding is borne out in larger prospective studies, surveillance strategies may need to be modified accordingly.

Functional brain mapping of monkey tool use.

When using a tool, we can perceive a psychological association between the tool and the body parts-the tool is incorporated into our "body-image." During tool use, visual response properties of bimodal (tactile and visual) neurons in the intraparietal area of the monkey's cerebral cortex were modified to include the hand-held tool. Visual properties of the monkey intraparietal neurons may represent the body-image in the brain. We explored tool use-induced activation within the intraparietal area and elsewhere in alert monkey brain using positron emission tomography (PET). Tool use-related activities compared with the control condition (simple-stick manipulation) revealed a significant increase in cerebral blood flow in the corresponding intraparietal region, basal ganglia, presupplementary motor area, premotor cortex, and cerebellum. These tool use-specific areas may participate in maintaining and updating the body-image for the precise guidance of a hand-held rake onto a distant reward.

Effect of endogenous dopamine on extrastriatal [¹¹C]FLB 457 binding measured by PET.

Central dopaminergic systems are known to be implicated in the pathophysiology of schizophrenia and recent in vivo dopamine receptor imaging studies have focused on the measurement of extrastriatal dopamine receptor. However, there are only a limited number of ligands that can measure the low-density D2 receptor in extrastriatal regions and their sensitivity to endogenous dopamine in extrastriatal regions has not yet been fully examined. In this study, the effect of endogenous dopamine on the extrastriatal binding of [11C]FLB 457 was examined in the rhesus monkey after facilitation with 1 mg/kg of methamphetamine (MAP) and was compared with the effect on the striatal binding of [11C]raclopride. The indices of receptor binding were obtained by four methods using cerebellum as a reference region. The bindings of [11C]FLB 457 in the frontal cortex, temporal cortex, and thalamus were not significantly changed after MAP treatment, while the striatal binding of [11C]raclopride was decreased by more than 20%. These results suggest that [11C]FLB 457 is not sensitive to endogenous dopamine in the extrastriatal regions of rhesus monkeys, despite a sufficient dose of MAP to decrease the binding of [11C]raclopride in the striatum.

[Antimicrobial susceptibility of Pseudomonas aeruginosa isolated in Fukushima Prefecture].

We investigated the susceptibility of Pseudomonas aeruginosa (isolated from the sputum of patients with respiratory infection in 4 medical institutions in Fukushima Prefecture) to 8 beta-lactam antibiotics including three carbapenems and relationships among MICs of antibiotics tested. The MIC90 values for a total of 216 strains were 6.25 micrograms/ml for meropenem, 12.5 micrograms/ml for imipenem and ceftazidime, 25 micrograms/ml for panipenem and cefsulodin, 50 micrograms/ml for cefpirome and over than 200 micrograms/ml for cefoperazone and piperacillin. The frequency of resistance of these strains to each antibiotic was as follows: The resistant strains were 19 (8.8%) for meropenem, 34 (15.7%) for imipenem and ceftazidime, 50 (23.1%) for cefsulodin, 72 (33.3%) for panipenem, 76 (35.2%) for piperacillin and 90 (41.7%) for cefpirome. Eighteen strains (18.3%) of 19 meropenem resitant straisn were resistant to imipenem and panipenem, but 16 strains of the 34 imipenem-resistant strains and 54 strains of the 72 panipenem-resistant strains were susceptible to meropenem. In investigation of isolation of multi-resistant Pseudomonas aeruginosa, the susceptibility of strains tested to 7 antibiotics except cefoperazone was as follows: The strains susceptible to all the 7 antibiotics were 92 strains (42.6%), and 33 strains (15.2%) were resistant to 2 antibiotics, 31 strains (14.4%) were resistant to 1 antibiotic, 21 strains (9.7%) were resistant to 3 antibiotics, 13 strains (6.0%) were resistant to 5 antibiotics, 9 (4.2%) were resistant to 4 and 7 antibiotics, and 8 strains (3.7%) were reistant to 6 antibiotics. Since the emergence of these multi-resistant strains is closely related to frequent use of antibiotics for nosocomial infections, special attention should be paid to the antimicrobial susceptibility of Pseudomonas aeruginosa and the situation of antibiotic resistant strains.

In vivo binding properties of [carbonyl-11C]WAY-100635: effect of endogenous serotonin.

[Carbonyl-(11)C]WAY-100635 has been reported to be a useful ligand for the investigation of 5-HT(1A) receptor imaging in vivo. However, the cellular distribution and the influence of endogenous serotonin (5-HT) on in vivo binding have not been fully examined. In this study, we investigated the effect of 5,7-dihydroxytryptamine-produced destruction of 5-HT neurons, reserpine-induced 5-HT depletion, and fenfluramine-induced 5-HT increase on [carbonyl-(11)C]WAY-100635 binding in vivo. There was no significant change in the uptake of [carbonyl-(11)C]WAY-100635 in the slice of 5-HT denervated rat brain except in the raphe nucleus, where 5-HT cell bodies exist. There was no obvious effect of enhanced 5-HT release by fenfluramine or decreased release by reserpine on [carbonyl-(11)C]WAY-100635 binding in the dissected brain region. No significant effect was observed in the time course of [carbonyl-(11)C]WAY-100635 in the hippocampus and frontal cortex measured by PET. These results indicated that the in vivo binding of [carbonyl-(11)C]WAY-100635 in the hippocampus and cerebral cortex mainly reflects postsynaptic 5-HT(1A) receptor binding, and that this binding is not sensitive to endogenous 5-HT.

Membrane topology of coronavirus E protein.

Coronavirus small envelope protein E has two known biological functions: it plays a pivotal role in virus envelope formation, and the murine coronavirus E protein induces apoptosis in E protein-expressing cultured cells. The E protein is an integral membrane protein. Its C-terminal region extends cytoplasmically in the infected cell and in the virion toward the interior. The N-terminal two-thirds of the E protein is hydrophobic and lies buried within the membrane, but its orientation in the lipid membrane is not known. Immunofluorescent analyses of cells expressing biologically active murine coronavirus E protein with a hydrophilic short epitope tag at the N-terminus showed that the epitope tag was exposed cytoplasmically. Immunoprecipitation analyses of the purified microsomal membrane vesicles that contain the same tagged E protein revealed the N-terminal epitope tag outside the microsomal membrane vesicles. These analyses demonstrated that the epitope tag at the N-terminus of the E protein was exposed cytoplasmically. Our data were consistent with an E protein topology model, in which the N-terminal two-thirds of the transmembrane domain spans the lipid bilayer twice, exposing the C-terminal region to the cytoplasm or virion interior.