Double-injection FDG method to measure cerebral glucose metabolism twice in a single procedure

[18F]fluorodeoxyglucose (FDG) and positron emission tomography (PET) may be used to examine changes in cerebral glucose metabolism in two physiological conditions. We proposed and evaluated a double injection-single session FDG method with biological constraints for this purpose. METHODS: Simulated brain time-radioactivity curves (TACs) generated by using a plasma TAC from an actual study and physiological combinations of input values in a kinetic model were analyzed to evaluate the accuracy of the proposed method. The reproducibility of the estimated values obtained by this method was tested in five normal volunteers who were studied with a dynamic PET scan and two injections of FDG in a single session while fasting. RESULTS: The simulation study showed that the estimated values obtained by the proposed method agreed well with the input values. In the human study, plasma glucose levels were 5.3 +/- 0.2 and 5.0 +/- 0.2 mM in the first and second measurements, respectively. The difference between the plasma glucose measurements was small but statistically significant (p < 0.05). Although no systematic deviations were noted in K*1 or rCMRglc, there were small deviations in K* (less than 10%) and LC (less than 5%) with a statistical significance (p < 0.01). CONCLUSION: The deviation between the measurements in K* and LC seemed to relate to the difference in the plasma glucose level. The double-injection FDG method with biological constraints can be used to estimate rCMRglc and LC sequentially in a single PET scanning session.     

Comprehensive investigation of disease‐specific short peptides in sera from patients with systemic sclerosis: Complement C3f‐des‐arginine,detected predominantly in systemic sclerosis sera,enhances proliferation of vascular endothelial cells

Objective

To identify pathogenic and/or disease‐specific short peptides in sera from patients with systemic sclerosis (SSc).

Methods

Serum samples from 40 patients with SSc, 30 patients with systemic lupus erythematosus, 21 patients with rheumatoid arthritis, 30 patients with osteoarthritis, and 26 healthy donors were tested. Short peptides with molecular weights of smaller than ∼3 kd, purified from the sera by magnetic bead–based hydrophobic interaction chromatography 18, were detected and their amino acid sequences determined using matrix‐assisted laser desorption ionization–time‐of‐flight mass spectrometry. Effects of the identified peptides on fibroblasts and microvascular endothelial cells were tested using synthesized peptides and sera containing the peptides.

Results

A group of peptides with mass/charge (m/z) values of 1,865, 1,778, 1,691, 1,563, and 1,450 were detected predominantly in the SSc sera. These peptides were identified as family members of complement C3f‐des‐arginine (DRC3f) derived from C3b. The level of DRC3f (m/z 1,865) was related to vascular involvement in SSc and to SSc disease activity. The synthesized peptides of DRC3f and C3f, as well as the filtrated sera containing DRC3f, enhanced proliferation of microvascular endothelial cells, but not fibroblasts. Both DRC3f and C3f increased production of transforming growth factor β1 by dermal microvascular endothelial cells.

Conclusion

This comprehensive peptidomics analysis revealed the predominance of DRC3f in the sera of patients with SSc. Investigation of DRC3f may be a useful tool for the diagnosis and evaluation of disease activity in SSc. Moreover, its demonstrated effects on endothelial cells suggest a potential role for DRC3f in the pathophysiologic mechanisms of SSc.

     

Lack of correlation between clinical characteristics and serum soluble Fas ligand levels in patients with multiple myeloma.

Multiple myeloma is characterized by the accumulation of malignant plasma cells in the bone marrow and rarely cured by chemotherapy. Villunger et al. showed that the neoplastic plasma cells express Fas ligand (FasL), which transmits a signal of apoptosis upon ligation to Fas, and suggested that the FasL suppresses the T-cells activated against malignant cells, resulting in escape from tumour immunity. We examined serum soluble FasL (sFasL) levels in 35 multiple myeloma patients to evaluate the correlation between sFasL levels and clinical characteristics. The serum sFasL levels were not affected by the disease status, serum monoclonal protein levels, or other prognostic factors. We could not determine whether the expression of FasL is involved in the poor clinical course of the disease.     

Clinical application of62Zn/62Cu positron generator: Perfusion and plasma pool images in normal subjects

We have developed a new⁶²Zn/⁶²Cu positron generator, and applied it for PET imaging of perfusion and plasma volume in 5 normal subjects. The generator makes it possible by a simple procedure to obtain⁶²Cu eluate and labeling compounds sufficiently every 40–60 minutes.⁶²Cu labeled pyruvaldehyde bis(N⁴-methylthiosemicarbazone) copper II (⁶²Cu-PTSM) was employed for cerebral and my ocardial perfusion imaging and⁶²Cu labeled human serum albumin-dithiosemicarbazone (⁶²Cu-HSA-DTS) was used for plasma pool imaging. The images of cerebral blood flow, cerebral plasma volume and myocardial perfusion were excellent. In addition, the analysis of tissue activity and blood activity demonstrated the microspheric character of⁶²Cu-PTSM. Correction of arterial activity with the standard disappearance curve of⁶²Cu-PTSM suggested the possibility of quantifying blood flow. The results of this study indicate the capability of the⁶²Zn/⁶²Cu generator for wide clinical use without an in-house cyclotron.     

A Case-Control Study of Gallstones: A Major Risk Factor for Biliary Tract Cancer

Because of the strong association between gallstones and biliary tract cancer, we conducted a case-control study of gallstones at Niigata Cancer Center Hospital. Eighty-six cases with gallstones (33 males and 53 females) and 116 hospital controls (56 males and 60 females) were surveyed by means of a self-administered questionnaire. Gallstones were categorized into cholesterol stones (25 cases) and pigment stones (30 cases) based on the appearance of the stones. In multivariate analyses based on an unconditional logistic regression model, the risk of total gallstones was positively associated with a taste for salty food (relative risk (RR)=2.31, 95% confidence interval (CI): 1.10–4.84), an intake of lettuce and cabbage (RR = 2.98, 95% CI: 1.47–6.06) and a family history of biliary diseases (RR=5.63, 95% CI: 1.76–17.95), and inversely associated with an intake of salted and dried fish (RR=0.16, 95% CI: 0.04–0.64). When analyzed by type of stones, cholesterol stones were associated with a taste for oily food (RR = 3.87, 95% CI: 1.36–11.03) and pigment stones were positively associated with professional or administrative occupation (RR = 4.74, 95% CI: 1.35–16.68) and inversely associated with a taste for less greasy food (RR = 0.28, 95% CI: 0.10–0.83). Some of these results are consistent with the results of our previous study on biliary tract cancer.     

Isolation,characterization, and family study of DTI,a novel partial D phenotype affecting the fourth external loop of D polypeptides

BACKGROUND: The Rh system is the most polymorphic of the blood group systems and is of major importance in transfusion medicine. The partial D phenotypes lack one or more of the D epitopes. These variants appear to have arisen through hybrid RhD-CE-D or by spontaneous point mutations in RhD. The serologic findings and the molecular characterization of a novel partial D phenotype, termed DTI, are presented here. STUDY DESIGN AND METHODS: RBCs from the DTI proband and RBCs from individuals with other partial D phenotypes were tested with MoAbs against 16 D epi- topes, according to the recommendations of the 4th ISBT Workshop on MoAbs (Rh Section 1A). A full-length cDNA encoding DTI and introns 4 and 5 of RhD were isolated and analyzed by DNA sequencing. A family study of the DTI allele was carried out using PCR-RFLP and long-range PCR methods. RESULTS: Analysis of RBCs from the proband revealed that the DTI phenotype lacks epitopes D1, D2.1 (partial), D2.2, D5, D6 (partial), and D8. The DTI polypeptide exhibits seven amino acid substitutions in the D polypeptide: F223V, A226P, E233Q, V238M, V245L, G263R, and K267M. The genomic organization of DTI showed that the replacement of RhD with RhCE was located in intron 4, and the replacement of RhCE with RhD was located in intron 5. Family studies revealed that the DTI allele was inherited maternally, whereas the RhD- allele was inherited paternally in the proband. CONCLUSION: The serologic data provide the first molecular characterization of DTI, a previously unknown partial D phenotype. This phenotype affected the D polypeptide within the fourth external loop, resulting in a new RhD-CE (entire exon 5)-D hybrid gene. It is worth noting that P226, encoded by exon 5, is derived from E of RhCE in the DTI polypeptide. Family studies demonstrated that DTI was associated with a cDTIE haplotype.     

Limited resection based on reclassification of segment 8 of the liver

Liver vein patterns which differ from those previously described are occasionally encountered during surgery. Therefore, we reclassified the anterosuperior segment (S8) into S8v (ventral area) and S8d (dorsal area), and the right paramedian sector into the ventral segment (S8v+S5) and the dorsal segment (S8d) based on portal and hepatic vein patterns. Using this new classification, we performed three types of limited resection of S8 in six patients with neither major nor minor procedural complications including biliary leaks, and no blood transfusion. This new classification allows development of surgical procedures where resection is limited to the portal unit and tumor.     

Incidence of Symptomatic Vertebral Fractures Among Newly Diagnosed Autoimmune Diseases Initiating Glucocorticoid Therapy

Few data are available regarding vertebral fracture risk in patients treated with corticosteroids including patients with interstitial lung disease (ILD). The aim of the present study was to identify risk factors for symptomatic vertebral fracture analyzed in patients with newly diagnosed autoimmune diseases.This was an observational cohort study conducted in the National Hospital Organization-EBM study group from 2006 to 2008. The study subjects were autoimmune disease patients who were newly treated with glucocorticoids (GCs). The primary endpoint was the first occurrence of vertebral fracture diagnosed by x-rays. Cox proportional-hazards regression was used to determine independent risk factors for vertebral fracture with covariates including sex, age, comorbidity, laboratory data, use of immunosuppressants, and dose of GCs. Survival was analyzed according to the Kaplan–Meier method and assessed by the log-rank test.Among 604 patients of mean age 59.5 years and mean GC dose 50.4 mg/d (first 1 months), 19 patient (3.1%) had at least 1 symptomatic vertebral fracture during 1.9 years of follow-up period. Cox regression model demonstrated that the relative risk for symptomatic vertebral fracture was independently higher in patient with ILD (hazard ratio [HR] = 2.86, 95% confidence interval [CI] = 1.10–7.42, P = 0.031) and in every 10-year increment of the age of disease onset (HR = 1.57, 95% CI = 1.09–2.26, P = 0.015). Kaplan–Meier analyses demonstrated that the incidence of vertebral fractures in patients with ILD was significantly higher in comparison with those without ILD.Our results indicate a higher risk of vertebral facture in patients with ILD and elderly patients during the initial GC treatment against autoimmune diseases. There is a need for further, even longer-term, prospective studies subjected patients with autoimmune disease, including ILD, under GC treatment.     

Risk of serious infection,malignancy, or death in Japanese rheumatoid arthritis patients treated with a combination of abatacept and tacrolimus: a retrospective cohort study

Clinical Rheumatology - To evaluate whether combinatorial use of abatacept (ABT) and tacrolimus (Tac) increases the risk of adverse events compared to their individual use in Japanese rheumatoid...