[Clinical evolution of patients with infection associated with orthopedic devices in treatment with continuous negative pressure]. / Evolución clínica de los pacientes con infección asociada a dispositivos ortopédicos en tratamiento con presión negativa continua.

Objective: To describe the use of negative pressure therapy with (TPNi) and without instillation (TPNs) as adjuvant treatment in the management of orthopedic device-associated infections (IADO). Method: Analytic observational study of records of patients with IADO managed with TPNi and TPNs with 0.9% saline solution, in patients > 18 years, operated on in 2018-2021. Clinical characteristics of infection, infectious agent as well as sociodemographic variables were evaluated. TPN was performed with the V.A.C. VERAFLO™ system. Analysis with χ2, Fisher and t-Student. Statistically accepted value p < 0.05. Results: Sample 40 patients. 75% male. Fractures 42.5% exposed and 57.5% closed. 92.5% applied prophylactic antibiotic (30-120 min). 35% plate implants, 12.5% centromedullary nail, 10% knee prosthesis and 12.5% hip. 47.5% bleeding < 500 ml. 72.5% surgical time of 2-4 hours. Previous hospitalization time, TPNs 3 weeks 55.9% and 4 weeks 26.5%; TPNi, 3 weeks 50% and 4 weeks 33.3%. Conservation of the implant 73.5% TPNs and 50% TPNi (p = 0.341). Wound closure 91.2% with TPNs and 100% with TPNi (p = 1.000). Conclusions: The use of TPNs and TPNi were useful as adjuvant treatments in the management of IADO, in addition they allowed to preserve the implant and wound closure in a large part of the patients.

Objetivo: Describir el uso de la terapia de presión negativa con (TPNi) y sin instilación (TPNs) como tratamiento adyuvante en el manejo de infecciones asociadas a dispositivo ortopédico (IADO). Método: Estudio observacional analítico de expedientes de pacientes con IADO manejados con TPNi y TPNs con solución salina al 0.9%, mayores de 18 años, operados en el periodo 2018-2021. Se evaluaron las características clínicas de infección, el agente infeccioso y las variables sociodemográficas. La TPN se realizó con sistema V.A.C.VERAFLO™. Para los análisis se emplearon las pruebas χ2, Fisher y t de Student. Valor estadísticamente aceptado: p < 0.05. Resultados: La muestra fue de 40 pacientes, el 75% masculinos. Fracturas: 42.5% expuestas y 57.5% cerradas. En el 92.5% se aplicó antibiótico profiláctico (30-120 min). Implantes: 35% placas, 12.5% clavo centromedular, 10% prótesis de rodilla y 12.5% cadera. El 47.5% con sangrado < 500 ml. En el 72.5% un tiempo quirúrgico de 2-4 horas. Tiempo de hospitalización previa: TPNs 3 semanas 55.9% y 4 semanas 26.5%; TPNi 3 semanas 50% y 4 semanas 33.3%. Conservación del implante: 73.5% TPNs y 50% TPNi (p = 0.341). Cierre de herida: 91.2% con TPNs y 100% con TPNi (p = 1.000). Conclusiones: El uso de TPNs y TPNi fue útil como tratamiento adyuvante en IADO, y además permitieron conservar el implante y el cierre de la herida en la mayoría de los pacientes.

A Japanese Multicenter Study on PET and Other Biomarkers for Subjects with Potential Preclinical and Prodromal Alzheimer's Disease.

BACKGROUND: PET (positron emission tomography) and CSF (cerebrospinal fluid) provide the "ATN" (Amyloid, Tau, Neurodegeneration) classification and play an essential role in early and differential diagnosis of Alzheimer's disease (AD). OBJECTIVE: Biomarkers were evaluated in a Japanese multicenter study on cognitively unimpaired subjects (CU) and early (E) and late (L) mild cognitive impairment (MCI) patients. MEASUREMENTS: A total of 38 (26 CU, 7 EMCI, 5 LMCI) subjects with the age of 65-84 were enrolled. Amyloid-PET and FDG-PET as well as structural MRI were acquired on all of them, with an additional tau-PET with 18F-flortaucipir on 15 and CSF measurement of Aß1-42, P-tau, and T-tau on 18 subjects. Positivity of amyloid and tau was determined based on the positive result of either PET or CSF. RESULTS: The amyloid positivity was 13/38, with discordance between PET and CSF in 6/18. Cortical tau deposition quantified with PET was significantly correlated with CSF P-tau, in spite of discordance in the binary positivity between visual PET interpretation and CSF P-tau in 5/8 (PET-/CSF+). Tau was positive in 7/9 amyloid positive and 8/16 amyloid negative subjects who underwent tau measurement, respectively. Overall, a large number of subjects presented quantitative measures and/or visual read that are close to the borderline of binary positivity, which caused, at least partly, the discordance between PET and CSF in amyloid and/or tau. Nine subjects presented either tau or FDG-PET positive while amyloid was negative, suggesting the possibility of non-AD disorders. CONCLUSION: Positivity rate of amyloid and tau, together with their relationship, was consistent with previous reports. Multicenter study on subjects with very mild or no cognitive impairment may need refining the positivity criteria and cutoff level as well as strict quality control of the measurements.

Exercise-induced hypercalcemia and vasopressin-mediated bone resorption.

Our human observational study showed that elevated arginine vasopressin levels by heavy exercise, not catecholamines, were associated with elevated serum tartrate-resistant acid phosphatase 5b (TRACP-5b). The increase in serum calcium was positively associated with percent changes of TRACP-5b, implying the involvement of bone resorption in the pathogenesis of exercise-induced hypercalcemia. INTRODUCTION: It remains unclear whether enhanced bone resorption explains exercise-induced hypercalcemia. An experimental study demonstrated that arginine vasopressin (AVP) stimulated osteoclast activity. METHODS: We conducted a prospective observational study, enrolling 65 trained healthy male officers of the Japan Self-Defense Forces (34 and 31 in waves 1 and 2, respectively). Before and after a 5-h heavy exercise, we collected laboratory data including bone markers, symptoms, and ionized calcium (iCa; wave 2 only). As blood calcium levels change after exercise, we estimated calcium (corrected calcium) levels immediately after the exercise using the correlation between blood calcium and time from the end of exercise in another cohort. RESULTS: Body weight decreased by 6.9% after the exercise. Corrected post-exercise serum total calcium (tCa) and iCa levels were significantly higher than pre-exercise levels, and 18% of participants showed hypercalcemia defined as corrected tCa >10.4 mg/dL or iCa >1.30 mmol/L. Serum tartrate-resistant acid phosphatase 5b (TRACP-5b), plasma three fractions of catecholamines, and AVP elevated significantly (median 14.3 pg/mL), while procollagen type 1 N-terminal propeptide and whole parathyroid hormone showed significant decreases. Corrected tCa increase showed a non-linear positive association with percent changes of TRACP-5b (%ΔTRACP-5b) even after adjustment for confounders. In addition, %ΔTRACP-5b was not associated with catecholamines, but with post-exercise AVP levels after adjustment for pre-exercise TRACP-5b. Symptoms of nausea or vomiting (observed in 20%) were positively associated with corrected post-exercise iCa after adjustment for post-exercise blood pH. CONCLUSION: AVP elevation may explain bone resorption and the following hypercalcemia in the setting of heavy exercise.

Automated PET-only quantification of amyloid deposition with adaptive template and empirically pre-defined ROI.

Amyloid PET is useful for early and/or differential diagnosis of Alzheimer's disease (AD). Quantification of amyloid deposition using PET has been employed to improve diagnosis and to monitor AD therapy, particularly in research. Although MRI is often used for segmentation of gray matter and for spatial normalization into standard Montreal Neurological Institute (MNI) space where region-of-interest (ROI) template is defined, 3D MRI is not always available in clinical practice. The purpose of this study was to examine the feasibility of PET-only amyloid quantification with an adaptive template and a pre-defined standard ROI template that has been empirically generated from typical cases. A total of 68 subjects who underwent brain (11)C-PiB PET were examined. The (11)C-PiB images were non-linearly spatially normalized to the standard MNI T1 atlas using the same transformation parameters of MRI-based normalization. The automatic-anatomical-labeling-ROI (AAL-ROI) template was applied to the PET images. All voxel values were normalized by the mean value of cerebellar cortex to generate the SUVR-scaled images. Eleven typical positive images and eight typical negative images were normalized and averaged, respectively, and were used as the positive and negative template. Positive and negative masks which consist of voxels with SUVR ⩾1.7 were extracted from both templates. Empirical PiB-prone ROI (EPP-ROI) was generated by subtracting the negative mask from the positive mask. The (11)C-PiB image of each subject was non-rigidly normalized to the positive and negative template, respectively, and the one with higher cross-correlation was adopted. The EPP-ROI was then inversely transformed to individual PET images. We evaluated differences of SUVR between standard MRI-based method and PET-only method. We additionally evaluated whether the PET-only method would correctly categorize (11)C-PiB scans as positive or negative. Significant correlation was observed between the SUVRs obtained with AAL-ROI and those with EPP-ROI when MRI-based normalization was used, the latter providing higher SUVR. When EPP-ROI was used, MRI-based method and PET-only method provided almost identical SUVR. All (11)C-PiB scans were correctly categorized into positive and negative using a cutoff value of 1.7 as compared to visual interpretation. The (11)C-PiB SUVR were 2.30 ± 0.24 and 1.25 ± 0.11 for the positive and negative images. PET-only amyloid quantification method with adaptive templates and EPP-ROI can provide accurate, robust and simple amyloid quantification without MRI.

Visual-statistical interpretation of (18)F-FDG-PET images for characteristic Alzheimer patterns in a multicenter study: inter-rater concordance and relationship to automated quantitative evaluation.

BACKGROUND AND PURPOSE: The role of (18)F-FDG-PET in the diagnosis of Alzheimer disease is increasing and should be validated. The aim of this study was to assess the inter-rater variability in the interpretation of (18)F-FDG-PET images obtained in the Japanese Alzheimer's Disease Neuroimaging Initiative, a multicenter clinical research project. MATERIALS AND METHODS: This study analyzed 274 (18)F-FDG-PET scans (67 mild Alzheimer disease, 100 mild cognitive impairment, and 107 normal cognitive) as baseline scans for the Japanese Alzheimer's Disease Neuroimaging Initiative, which were acquired with various types of PET or PET/CT scanners in 23 facilities. Three independent raters interpreted all PET images by using a combined visual-statistical method. The images were classified into 7 (FDG-7) patterns by the criteria of Silverman et al and further into 2 (FDG-2) patterns. RESULTS: Agreement among the 7 visual-statistical categories by at least 2 of the 3 readers occurred in >94% of cases for all groups: Alzheimer disease, mild cognitive impairment, and normal cognitive. Perfect matches by all 3 raters were observed for 62% of the cases by FDG-7 and 76 by FDG-2. Inter-rater concordance was moderate by FDG-7 (κ = 0.57) and substantial in FDG-2 (κ = 0.67) on average. The FDG-PET score, an automated quantitative index developed by Herholz et al, increased as the number of raters who voted for the AD pattern increased (ρ = 0.59, P < .0001), and the FDG-PET score decreased as those for normal pattern increased (ρ = -0.64, P < .0001). CONCLUSIONS: Inter-rater agreement was moderate to substantial for the combined visual-statistical interpretation of (18)F-FDG-PET and was also significantly associated with automated quantitative assessment.

FDG PET/CT features of ovarian metastasis.

AIM: To assess the characteristics of [(18)F]-fluoro-2-deoxy-d-glucose (FDG) uptake in cases of ovarian metastasis using positron-emission tomography/computed tomography (PET/CT). MATERIALS AND METHODS: Twelve patients with 16 ovarian metastases arising from colon cancer (n=6), breast cancer (n=4), gastric cancer (n=3), and pancreatic cancer (n=3) who underwent FDG-PET/CT examination were included in this study. The effect of lesion size and morphological pattern (predominantly solid or cystic) on FDG uptake was evaluated using the quantitative standardized uptake value (SUV). RESULTS: The mean maximum SUV for the 16 lesions was 4.6±2.4 (range 1.8∼9.9). The Pearson correlation coefficient test showed no significant correlation between maximum SUV and lesion size (r=0.21, p=0.42). The maximum SUV of solid (n=5) and cystic (n=11) lesions was 5.5±2.7 and 4.3±2.2, respectively, and the difference was not significant (p=0.43). Breast cancer showed the highest maximum SUV (6.4±3.6), followed by colon cancer (5.3±1.4), gastric cancer (3.3±0.5), and pancreatic cancer (2.2±0.6). CONCLUSION: Ovarian metastases show a variable maximum SUV with mild to intense FDG uptake.

Validation and standardization of virus neutralizing test using indirect immunoperoxidase technique for the quantification of antibodies to rabies virus.

A virus neutralizing test using an indirect immunoperoxidase technique (VNT-IIP) for rabies has been developed for the titration of dog and cat serum samples in Japan. The VNT-IIP has the advantage that results obtained can be viewed by the naked eye. The purpose of this study was to validate the VNT-IIP and compare it with one of the international standard methods, the fluorescent antibody virus neutralization test (FAVNT). The VNT-IIP showed satisfactory repeatability, high analytical specificity and good accuracy. Regarding the comparison between the VNT-IIP and the FAVNT, the VNT-IIP showed good agreement (91.9%), high sensitivity (92.8%) as well as specificity (87.0%) and good correlation (r = 0.92). As described above, the validation of the VNT-IIP was satisfactory and the performances of the test proved to be equivalent to those of an international standard method.

Development of a GSO positron/single-photon imaging detector.

We have developed and tested a GSO (gadolinium oxyorthosilicate) position-sensitive gamma detector which can be used with positron and single-photon radionuclides for imaging breast cancer or sentinel lymph node detection. Because GSO has a relatively good energy resolution for annihilation gammas as well as low energy gamma photons, and does not contain any natural radioisotopes, it can be used for positron imaging and lower energy single-photon imaging. The imaging detector consists of a GSO block, 2 inch square multi-channel position-sensitive photo-multiplier tube (PSPMT), and associated electronics. The size of a single GSO element was 2.9 mm x 2.9 mm x 20 mm and these elements were arranged into 15 x 15 matrixes to form a block that was optically coupled to the PSPMT. It was possible to separate all GSO crystals into a two-dimensional position histogram for annihilation gammas (511 keV) and low energy gamma photons (122 keV). The typical energy resolution was 24% FWHM and 37% FWHM for 511 keV and 122 keV gamma photons, respectively. For the positron imaging, coincidence between the imaging detector and a single gamma probe is measured. For the single-photon imaging, a tungsten collimator is mounted in front of the imaging detector. With this configuration, it was possible to image both positron radionuclides and low energy single-photon radionuclides. We measured spatial resolution and sensitivity as well as image quality of the developed imaging detector. Results indicated that the developed imaging detector has the potential to be a new and useful instrument for nuclear medicine.

Efficacy of an inactivated feline panleucopenia virus vaccine against a canine parvovirus isolated from a domestic cat.

Canine parvovirus type 2a (CPV-2a) and type 2b (CPV-2b) have recently been isolated from cats throughout the world, and CPV-2b strain FP84 has been reported to be virulent in domestic cats. Although live feline panleucopenia virus (FPLV) vaccines protect domestic cats from CPV infection, the efficacy of inactivated FPLV vaccines has not been established. In this study, two domestic cats were vaccinated with a commercial inactivated FPLV vaccine and challenged with CPV-2b strain FP84 isolated from a domestic cat. The cats were protected against CPV-2b strain FP84 infection and their clinical signs were suppressed, although the two unvaccinated cats showed the typical clinical signs of parvovirus infection.

Severe haemodynamic stress in selected subtypes of patients with moyamoya disease: a positron emission tomography study.

BACKGROUND: The optimum management of patients with moyamoya disease remains controversial. OBJECTIVES: To examine retrospectively the correlation between the degree of haemodynamic stress and the clinical presentation by measuring cerebral haemodynamics and metabolism using positron emission tomography (PET). METHODS: 57 patients with moyamoya disease (mean age 32 years, range 12 to 64), classified into five groups according to clinical manifestations, underwent PET measurement of cerebral blood flow (CBF), cerebral blood volume (CBV), cerebral metabolic rate for oxygen (CMR(O2)), and oxygen extraction fraction (OEF) using (15)O labelled gases. The regional values in patient groups were compared with a normal group. RESULTS: CBF in non-symptomatic patients, patients presenting with transient ischaemic attacks (TIA), and patients with haemorrhagic onset (H) was not significantly lower than in normal controls in any region. CBV in the TIA group and in patients with infarction associated with TIA (I/TIA) was significantly higher than in the controls in most regions. OEF in the frontal, parietal, and temporal cortex was significantly higher in the I/TIA group than in the controls. Patients in the H group and those with a permanent deficit with infarction (PD group) had decreased metabolism with normal OEF. Multivariate analysis to test the distribution of the three dimensional vector (CBF, CBV, OEF) showed significant differences between every possible pair among the six groups except NS v H and H v PD in the frontal cortex. CONCLUSIONS: The haemodynamic status of moyamoya disease is not uniform, and severe haemodynamic stress occurs in selected subgroups of patients.

Molecular linkage mapping and phylogeny of the chalcone synthase multigene family in soybean.

Chalcone synthase (CHS), the key enzyme in the flavonoid biosynthesis pathway, is encoded by a multigene family, CHS1-CHS8 and dCHS1 in soybean. A tandem repeat of CHS1, CHS3 and CHS4, and dCHS1 that is believed to be located in the vicinity comprises the I locus that suppresses coloration of the seed coat. This study was conducted to determine the location of all CHS members by using PCR-based DNA markers. Primers were constructed based on varietal differences in either the nucleotide sequence of the 5'-upstream region or the first intron of two cultivars, Misuzudaizu, with a yellow seed coat (II), and Moshidou Gong 503, with a brown seed coat (ii). One hundred and fifty recombinant inbred lines that originated from a cross between these two cultivars were used for linkage mapping together with 360 markers. Linkage mapping confirmed that CHS1, CHS3, CHS4, dCHS1, and the I locus are located at the same position in molecular linkage group (MLG) A2. CHS5 was mapped at a distance of 0.3 cM from the gene cluster. CHS2 and CHS6 were located in the middle region of MLGs A1 and K, respectively, while CHS7 and CHS8 were found at the distal end of MLGs D1a and B1, respectively. Phylogenetic analysis indicated that CHS1, CHS3, CHS4, and CHS5 are closely related, suggesting that gene duplication may have occurred repeatedly to form the I locus. In addition, CHS7 and CHS8 located at the distal end and CHS2, CHS6, and CHS members around the I locus located around the middle of the MLG are also related. Ancient tetraploidization and repeated duplication may be responsible for the evolution of the complex genetic loci of the CHS multigene family in soybean.

Midbrain hypometabolism as early diagnostic sign for progressive supranuclear palsy.

OBJECTIVE: Progressive supranuclear palsy (PSP) is often misdiagnosed in early phase. The purpose of this study is to investigate the feature of [(18)F]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography images for the early diagnosis of PSP. METHODS: We studied 15 patients with PSP and 16 normal subjects. Using SPM99 and analysis of covariance to eliminate the effect of aging, the differences between PSP and normals were displayed as a statistical map. In the PSP, we also investigated the correlation with duration and with the subscores of Unified Parkinson's Disease Rating Scale. RESULTS: The glucose metabolism of midbrain was significantly lower in PSP than in normals. However, correlation was not found between the metabolism of midbrain and clinical deterioration. CONCLUSIONS: The statistical map clearly demonstrated the hypometabolism of midbrain in PSP, which is independent of the clinical deterioration. The hypometabolism of midbrain is one of the most promising sign for early diagnosis of PSP.

Longitudinal follow-up study of adenoviral vector-mediated gene transfer of dopamine D2 receptors in the striatum in young, middle-aged, and aged rats: a positron emission tomography study.

Overexpression of dopamine D(2) receptors by adenoviral vector-mediated gene transfer in the rat striatum was evaluated by positron emission tomography in vivo and by ex vivo autoradiography in 5-, 13-, and 24-month-old Fischer 344 rats. Each rat had hemilateral gene transfer of D(2) receptors mediated by adenoviral vectors (AdCMV.DopD(2)R) in the striatum with contralateral striatal injection of control vectors (AdCMV.LacZ). At day 2 or 3 after vector injection positron emission tomography or ex vivo autoradiography was performed. The binding potential of a radiolabeled D(2) receptors ligand, [11C]raclopride, was significantly higher in the D(2) receptors gene-transferred striatum than the control side in each age group at a similar degree. The binding potential in the AdCMV.DopD(2)R-injected striatum of 24-month-old rats was similar to that in the AdCMV.LacZ-injected striatum of 5-month-old rats (0.99+/-0.14 versus 0.91+/-0.08). A significant age-associated decrease of the binding potential of [11C]raclopride was found in the control vector-injected side, and a significant increase of the binding potential in the adenoviral vector-injected side in all three age groups, suggesting no aging effect on the overexpression of D(2) receptors. A group of rats underwent follow-up assessment by positron emission tomography. The overexpression of D(2) receptors decreased with time in all three groups; however, the decrease rate of the D(2) receptors expression was significantly smaller in the 24-month-old group than in the 5-month-old group. We confirmed that the adenoviral vector-mediated gene transfer of D(2) receptors compensated the decreased density of striatal D(2) receptors in the 24-month-old rats up to the level in the control striatum of 5-month-old rats, and the decrease rate of the overexpression was significantly smaller in aged rats.

Meningio-angiomatosis in a patient with focal epilepsy: value of PET in diagnoses and preoperative planning of surgery.

A 17-year-old boy with epileptic seizures due to meningio-angiomatosis without neurofibromatosis type 2 is presented. Low grade astrocytoma in the left temporal lobe was resected when he was 11 years old. A recurrence was suspected on following-up MRI and a positive PET scan with 11C-methionine PET 6 years later around the resected area. The language area was mapped using H2(15)O PET activation technique. The lesion was completely resected while preserving the verbal area assisted by three-dimensional imaging protocol of MR-registered PET. The patient was well and seizure-free for 8 years thereafter without antiepileptic drugs. Histologically, there was an increase of dilated arterioles and meningothelial cell-like spindle cells around them, which are characteristic pathological features of meningio-angiomatosis. It is most likely that angiomatous tissue developed perivascular meningiomatous components and formed the meningio-angiomatosis in our presented case. In addition, we presented our protocol of functional neuro-imaging which was useful in terms of the functional neurosurgery.

PET neuroreceptor imaging as predictor of severe cerebral ischemic insult.

Measurement of the adenosine A1 receptor (A1-R) with positron emission tomography (PET) using a newly developed positron ligand, [1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX). were performed in a cat middle cerebral artery (MCA) occlusion and reperfusion. Eighteen adult cats underwent PET measurement of; 1) cerebral blood flow (CBF). 2) A1-R, 3) central benzodiazepine receptor (BDZ-R) and 4) glucose metabolism with 15O labeled water, MPDX, 11C-flumazenil (FMZ) and 18F-fluorodeoxyglucose (FDG), respectively. The CBF, A1-R, BDZ-R and FDG uptake were serially measured after 60 min occlusion of MCA in this order. MPDX binding and FMZ binding, but not CBF and FDG uptake, were significantly reduced in the groups with severer ischemic insult than in the groups with no or milder insults. Of the two receptor ligands, the reduction rate of the MPDX binding to A1-Rs was larger in a group that caused fatal ischemic insult. The newly developed PET in vivo imaging technique using MPDX was suitable in evaluating the function of adenosine and A1-Rs in relation to cerebral ischemia.

Fast formation of statistically reliable FDG parametric images based on clustering and principal components.

Formation of parametric images requires voxel-by-voxel estimation of rate constants, a process sensitive to noise and computationally demanding. A model-based clustering method for a two-parameter model (CAKS) was extended to the FDG three-parameter model. The concept was to average voxels with similar kinetic signatures to reduce noise. Voxel kinetics were categorized by the first two principal components of the tissue time-activity curves for all voxels. k2 and k3 were estimated cluster-by-cluster, and K1 was estimated voxel-by-voxel within clusters. When CAKS was applied to simulated images with noise levels similar to brain FDG scans, estimation bias was well suppressed, and estimation errors were substantially smaller--1.3 times for Ki and 1.5 times for k3-than those of conventional voxel-based estimation. The statistical reliability of voxel-level estimation by CAKS was comparable with ROI analysis including 100 voxels. CAKS was applied to clinical cases with Alzheimer's disease (ALZ) and cortico basal degeneration (CBD). In ALZ, the affected regions had low Ki (K1k3/(k2 +k3)) and k3. In CBD, Ki was low, but k3 was preserved. These results were consistent with ROI-based kinetic analysis. Because CAKS decreased the number of invoked estimations, the calculation time was reduced substantially. In conclusion, CAKS has been extended to allow parametric imaging of a three-compartment model. The method is computationally efficient. with low bias and excellent noise properties.

Synthesis and evaluation of [18F]fluoroethyl SA4503 as a PET ligand for the sigma receptor.

The sigma receptor might be involved in several diseases in the central nervous system. It occurs in the endocrine, immune, and other peripheral organ systems and is expressed in a variety of human tumors. The [18F]fluoroethyl analog of the sigma1-selective ligand SA4503 ([18F]FE-SA4503) was prepared and evaluated in animals to investigate its suitability for in vivo measurement of sigma receptors with positron emission tomography (PET). [18F]FE-SA4503 was synthesized by [18F]fluoroethylation of the corresponding O-demethyl precursor in an overall radiochemical yield of 4-7% (EOB) with a specific activity of >100 TBq/mmol. The radioligand had higher in vitro affinity for the sigma receptor than SA4503 (IC(50) sigma1 6.48 nM, IC50 sigma2 2.11 nM). [18F]FE-SA4503 was injected into mice. Uptake could be blocked by co-injection of the sigma receptor ligands haloperidol, pentazocine, and cold SA4503, but not with other receptor ligands. Ex vivo autoradiography studies in rats showed regional distribution in the brain similar to [11C]SA4503. Hippocampus, thalamus, and cortical areas were clearly delineated by [18F]FE-SA4503. The uptake was blocked by SA4503 treatment. In the rat brain, only a small portion of metabolites (6.6% of brain radioactivity) was detected at 30 min postinjection, whereas in plasma the fraction of metabolites amounted to 51.3% of plasma radioactivity. The kinetics of [18F]FE-SA4503 was measured with PET in the conscious monkey brain. High uptake values were found in the cortex, thalamus, cerebellum, and striatum, reaching a plateau value at 30 min postinjection. It is concluded that [18F]FE-SA4503 showed specific binding to sigma receptors in three animal species.

Origin of cytoplasm substituted rice cultivars found in Japan.

Genetic variation of Japanese rice cultivars were examined. Five of 450 lowland cultivars and another five of 200 upland cultivars were determined as the indica type by using isozyme genotypes and the remainder were of the japonica type. The major characteristics of these indica cultivars, revealed a slender shape of grains, a short apiculus hair length, a positive allele for Ph reaction, and allele-3 for the Pgd1 locus. Three of these indica cultivars showed a non-deletion ORF100, which is essential to the japonica-type plastid. The plastid subtype identity (PS-ID) sequences of these plastids is 6C7A, which is also a japonica-specific repeat unit. Thus, these cultivars were concluded to be naturally generated cytoplasm substituted lines. These plastids were introduced into a indica genetic background from japonica cultivars grown elsewhere. The rest of the indica cultivars revealed a deletion-type ORF100 and plastid subtype 8C8A, both of which are indica-specific. These cultivars carried indica-type allelic constitutions for diagnostic isozyme loci. However, other characters were identical to the cytoplasm-substituted cultivars in Japan. In East and Southeast Asia, cultivars carrying a indica-type nuclear genotype with a japonica-type plastid are restricted to Aus cultivars in the Bengal region. Genetic and historical records suggest that Japanese indica cultivars and the Aus cultivars are closely related. The Aus cultivars acquire necessary genetic constitutions from both indica and japonica cultivars through naturally occurring out-crossing to adapt to a particular cultivation condition in the region. The wide adaptability enabled them to be introduced into a northern region like Japan.