Genetic basis of autoimmune disease in MRL/lpr mice: dissection of the complex pathological manifestations and their susceptibility loci

MRL/MpJ-lpr/lpr (MRL/lpr) mice spontaneously develop various forms of autoimmune disease in the same individuals, including glomerulonephritis, polyarteritis, arthritis and sialoadenitis. An MRL recombinant congenic strain of mice bearing the gld gene, MRLiMpTn-gld/gld (MRL/gld), also develops lesions similar to those in MRL/lpr mice. The lpr and gld genes are a Fas deletion mutant and a Fas ligand mutant, respectively. Thus, autoimmune disease in these mice seemed to be a single gene disease involving the complex pathological manifestations as pleiotropy. However, comparative studies with C3H/HeJ and C57BL/6J strains of mice bearing lpr or gld revealed that these lesions developed only in mice with an MRL background. Moreover, these lesions were genetically segregated among MRL/lpr x (MRL/lpr x C3H/lpr)F1 mice. This indicates that an MRL strain has particular gene(s) affecting the development of each lesion. Association studies of each lesion with polymorphic microsatellite markers using backcross mice revealed that gene loci responsible for each lesion exist at different chromosomal positions and have additive and hierarchical properties of polygenic inheritance for some of the lesions. We conclude that the complex pathological manifestations of autoimmune disease are under the control of different combinations of polygenes.     

Preliminary study of correction of original metal artifacts due to 1-125 seeds in postimplant dosimetry for prostate permanent implant brachytherapy

Purpose We investigated a subtraction-based reprojection approach to reduce CT metal artifacts due to I-125 seeds and evaluated the clinical implications in postimplant dosimetry for prostate permanent implant brachytherapy. Materials and Methods The raw projection data were used to reduce metal artifacts due to I-125 seeds. CT images of the metal parts only were separated from the original CT images by setting the threshold for pixel value to that of the I-125 seeds. Using these images, sinograms of CT images with and without seeds were obtained by inverse Radon transform (iRT), and the sinogram of the metal image was subtracted from that of the original image. Finally, the image was reconstructed using the sinogram by Radon transform (RT). This technique was applied to a prostate phantom and to a patient undergoing prostate permanent implant brachytherapy. Results Metal artifacts from I-125 seeds were reduced in both the phantom and patient studies. This technique decreased the density of the inner region of seeds but enhanced the density of the seed edge, thereby facilitating the identification of seed number, orientation, and location. Conclusion This method reduces metal artifacts from I-125 seeds, and has potential for decreasing the time required for and improving the accuracy of postimplant dosimetry. This study was partly supported by a Grant-in-Aid for Scientific Research (Grant No. 177908826807) of the Japan Society for the Promotion of Science (JSPS).     

The adenosine A2A receptor is associated with methamphetamine dependence/psychosis in the Japanese population

Background

Suicide and major depressive disorders (MDD) are strongly associated, and genetic factors are responsible for at least part of the variability in suicide risk. We investigated whether variation at the tryptophan hydroxylase-2 (TPH2) gene rs7305115 SNP may predispose to suicide attempts in MDD.

Methods

We genotyped TPH2 gene rs7305115 SNP in 215 MDD patients with suicide and matched MDD patients without suicide. Differences in behavioral and personality traits according to genotypic variation were investigated by logistic regression analysis.

Results

There were no significant differences between MDD patients with suicide and controls in genotypic (AG and GG) frequencies for rs7305115 SNP, but the distribution of AA genotype differed significantly (14.4% vs. 29.3%, p < 0.001). The G-allele frequency was significantly higher in cases than control group (58.1% vs.45.6%, p < 0.001), but the A-allele carrier indicated a decreased trend in MDD with suicide behaviors than control group (41.9% vs.54.4%, p < 0.001). The multivariate logistic regression analysis indicated that TPH2 rs7305115 AA (OR 0.33, 95% CI 0.22-0.99), family history of suicide (OR 2.98, 95% CI 1.17-5.04), negative life events half year ago (OR 6.64, 95% CI 2.48-11.04) and hopelessness (OR 7.68, 95% CI 5.79-13.74) were significantly associated with the suicide behaviors in MDD patients.

Conclusions

The study suggested that hopelessness, negative life events and family history of suicide were risk factors of attempted suicide in MDD while the TPH2 rs7305115A remained a significant protective predictor of suicide attempts.     

Indication of repeat prostate biopsy for the diagnosis of prostate cancer

There is no standard criterion for repeat prostate biopsy in cases with a negative initial biopsy. We retrospectively analyzed our experience of repeat prostate biopsy to establish its indication for the diagnosis of prostate cancer. From April 1997 to March 2005, 35 consecutive patients underwent repeat prostate biopsy at the department of Urology, Asahikawa Medical College Hospital because of clinically suspicious prostate cancer despite a negative initial biopsy. We compared patients' age, number of cores obtained during repeat biopsy, digital rectal examination findings, total prostate volume, the time from the first to the last biopsy, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity between cancer-positive and cancer-negative groups. Prostate cancer was detected in 17 of 35 patients (49%). Fifteen patients with prostate cancer were diagnosed by the first repeat biopsy and other 2 patients were diagnosed by the second repeat biopsy. A statistically significant difference was only noted in age and PSA density. Persistently elevated total PSA and a higher PSA density in cases with a negative initial biopsy might be a good indication of repeat prostate biopsy for the diagnosis of prostate cancer.     

The role of thallium-201 single photon emission tomography in the investigation and characterisation of brain tumours in man and their response to treatment

The aim of this study was to characterise brain tumour type and treatment response in relation to the uptake of thallium-201.²⁰¹Tl single photon emission tomography (SPET) was performed in 58 patients with brain tumours. Fifty-six patients were utilised for the statistical comparison of the early and delayed²⁰¹Tl indices expressed as the ratio of tumour to contralateral cerebral hemisphere uptake. The retention index of²⁰¹Tl in the tumour tissue calculated from the early and delayed scans was also analysed. Furthermore, in 56 patients with 58 brain tumours, a comparison was made of the diagnostic value of high²⁰¹Tl uptake and gadolinium diethylene triamine penta-acetic acid (Gd-DTPA) enhancement on MRI scans. Although high²⁰¹Tl uptake was observed in viable malignant gliomas, brain metastases, meningiomas and malignant teratoma, the viable malignant gliomas could not be differentiated from brain metastases and extracerebral tumours by means of²⁰¹Tl indices.²⁰¹Tl SPET failed to diagnose a viable ring-enhanced tumour with a thin rim and small tumours of less than 1.5 cm in diameter visualised by Gd-DTPA-enhanced MRI. In spite of this,²⁰¹Tl SPET appears to be effective for determination of the malignant viability of tumours     

Cerebral radiation necrosis with accumulation of thallium 201 on single-photon emission CT.

A patient who had previously undergone resection of a malignant glioma followed by radiation therapy was found to have a focus of a high accumulation of thallous chloride Tl 201 on single-photon emission CT scans, suggesting recurrent tumor. Resection of this area was performed and the specimen showed radiation necrosis, including such reactive changes as reactive astrocytes and lymphocytes in the necrotic tissue. This case illustrates a diagnostic pitfall in the use of 201Tl single-photon emission CT for distinguishing radiation necrosis from recurrent tumor in patients treated for malignant glioma.     

Clinical characteristics and treatment responses in new-onset epilepsy in the elderly

PurposeEpidemiologic studies have shown that the incidence of epilepsy is the highest in the elderly population. Because the elderly constitutes the most rapidly growing population, epilepsy in this group is an important health issue worldwide. To identify the characteristics of epilepsy in the elderly, we reviewed our experience at a tertiary referral center in Japan.MethodsWe searched all electronic medical records of the past 6 years at the epilepsy clinic of the hospital affiliated to our University-affiliated hospital. We defined an elderly person as an individual aged 65 years and above. All patients underwent history and physical examinations, 3 T magnetic resonance imaging and/or computer tomography, and electroencephalogram (EEG). The diagnosis of epilepsy, age of onset, etiology, and antiepileptic medication were recorded.ResultsWe identified 70 patients who developed epilepsy after the age of 65 years. The mean age of seizure onset was 73.1 years and 52.9% patients were males. Complex partial seizures (CPS) without secondarily generalization (n = 33, 47.1%) were most frequent. The most frequent diagnosis was temporal lobe epilepsy (n = 50, 71.4%). Etiological diagnosis was possible in nearly 50% patients, including those with cerebrovascular disease. A clear cause of epilepsy was not found (i.e., non-lesional epilepsy) in 52.8% patients. Interictal EEG revealed focal epileptiform discharges in 72.9% (n = 51) patients. Of the 54 patients who were followed more than 1 year, 42 patients (77.8%) were on antiepileptic monotherapy and 52 patients (96.3%) had been seizure-free for more than 1 year.ConclusionThe most frequent diagnosis in our cohort of elderly persons with new-onset epilepsy was temporal lobe epilepsy. Non-lesional temporal lobe epilepsy was not uncommon. Epileptogenecity was relatively low in elderly patients and they responded well to antiepileptic medication.     

Reading in a regular orthography: an FMRI study investigating the role of visual familiarity

In order to separate the cognitive processes associated with phonological encoding and the use of a visual word form lexicon in reading, it is desirable to compare the processing of words presented in a visually familiar form with words in a visually unfamiliar form. Japanese Kana orthography offers this possibility. Two phonologically equivalent but visually dissimilar syllabaries allow the writing of, for example, foreign loanwords in two ways, only one of which is visually familiar. Familiarly written words, unfamiliarly written words, and pseudowords were presented in both Kana syllabaries (yielding six conditions in total) to participants during an fMRI measurement with a silent articulation task (Experiment 1) and a phonological lexical decision task (Experiment 2) using an event-related design. Consistent over two experimental tasks, the three different stimulus types (familiar, unfamiliar, and pseudoword) were found to activate selectively different brain regions previously associated with phonological encoding and word retrieval or meaning. Compatible with the predictions of the dual-route model for reading, pseudowords and visually unfamiliar words, which have to be read using phonological assembly, caused an increase in brain activity in left inferior frontal regions (BA 44/47), as compared to visually familiar words. Visually familiar and unfamiliar words were found to activate a range of areas associated with lexico-semantic processing more strongly than pseudowords, such as the left and right temporo-parietal region (BA 39/40), a region in the left middle/inferior temporal gyrus (BA 20/21), and the posterior cingulate (BA 31).     

Leiomyosarcoma of the Pancreas: Report of a Case Diagnosed by Fine Needle Aspiration Biopsy

We present a case of pancreatic leiomyosarcoma with liver metastasisdiagnosed by liver tumor biopsy. A 66-year-old man had a pancreatictumor and hepatic tumors, which were hypoechoic and mixed echoicon ultrasonography, respectively. They were stained in enhancedcomputed tomography and angiography. A fine needle aspirationbiopsy of the liver tumor was performed, and the pathologicalexamination of the biopsied specimen suggested the tumor cellsto have originated from smooth muscle. Under a diagnosis ofpancreatic leiomyosarcoma with liver metastasis, the patientwas treated with several anticancer agents. The tumor, however,spread to multiple organs and he dies of the disease two yearsnine months after the start of treatment. The diagnosis of pancreaticleiomyosarcoma was confirmed by autopsy.