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e15103Background: It has been previously documented that high somatic mutational rates in cancer as determined by whole genome sequencing correlates with high microsatellite instability (MSI-H) and...

We examined aged and young monkeys using a multiple position reversal task to investigate declines in cognitive functions with aging. The task consisted of an original learning task (simple position discrimination task) and a reversal learning task. While the performance of the aged monkeys was not different from that of the young monkeys in the original learning task, the aged monkeys showed a poorer performance than the young monkeys in the reversal learning task. According to our response analysis, the poor performance of aged monkeys in the reversal learning was not caused mainly by repetition of error responses, but rather by the impairment of understanding of the association between stimulus and reward. These results suggest that the prefrontal cortex, particularly the medial orbital cortex, is impaired with aging.

low or below reference ranges. Vitamin A was associated with sex, metastases, CRP and albumin (all p < 0.01). Vitamin B1 was associated with venous invasion and WCC (p < 0.05 and

Parkinson's disease (PD) is a progressive movement disorder marked by selective degeneration of dopaminergic neurons of the substantia nigra and severe decrease in the dopamine (DA) content of the striatum. Replacement of DA is important to alleviate the motor symptoms of the disease. The DA precursor, L-3,4-dihydroxyphenylalanine (L-dopa), which is converted to DA by aromatic L-amino acid decarboxylase (AADC), provides clinical benefit to virtually all patients and has been mainstay in pharmacotherapy for PD. However, as the disease progresses, severe loss of dopaminergic nerve terminals is associated with an 80–95% depletion of striatal AADC activity resulting in loss of L-dopa efficacy. We demonstrated previously that AAV vector-mediated gene transfer of three DA-synthesizing enzymes, namely tyrosine hydroxylase, AADC, and GTP cyclohydrolase I, resulted in behavioral recovery in animal models of PD with efficient and long-term transduction of striatal neurons. In the present experiments, we investigated the therapeutic potential of the combination therapy, gene transfer of AADC with oral administration of L-dopa, in a primate bilateral model of PD. Cynomolgus macaques (Macaca fascicularis) were chronically treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) to make bilateral striatal lesions. Animals became behaviorally stable and motor symptoms did not ameliorate by the administration of L-dopa with peripheral AADC inhibitor. Then, adeno-associated virus (AAV) vector expressing AADC was injected into the unilateral putamen stereotaxically. Expression of AADC in the unilateral putamen resulted in remarkable improvement in manual dexterity on the contralateral to the AAV-AADC-injected side after the oral administration of L-dopa with peripheral AADC inhibitor. Fine motor task consists of capturing a piece of an apple improved on the contralateral hand with L-dopa. Amelioration of motor symptoms persisted about four hours each time after the oral intake of L-dopa. This duration of efficacy corresponds to the effective blood concentrations of the drug. Positron emission tomography showed remarkable and persistent increase of [11C]-L-dopa uptake in the AAV-AADC injected putamen. Gene transfer of AADC alone in combination with oral administration of L-dopa could be a shortcut to starting clinical trials of gene therapy for PD. With this method, patients still need to take L-dopa for the control of PD symptoms, but DA production can be regulated by the dose of L-dopa.

牛肉の肉質と蓄積脂肪の性質は密接な関連のあることが知られている.本研究は,東北地方で飼養頭数の増加している肉牛である日本短角種若令去勢肥育牛6頭(奥羽種畜牧場において種雄牛の後代検定に供されたもの)の,第7～8助骨間の横断面における皮下脂肪,筋肉間脂肪,ロース芯内交雑脂肪からなる筋肉内脂肪,および腎臓脂肪のトリグリセリド(TG)の構成脂肪酸および分子量分布を,ガスクロマトグラフィー(GC)によって,調査した.TGの脂肪酸組成のC18:1/C18:0値を部位別に比較した場合,皮下脂肪(3.35)は腎臓脂肪(1.23)の約2.7倍であった.筋肉内および筋肉間の同値は,皮下脂肪と腎臓脂肪の中間の値を示した.TGの炭素数分布は,腎臓脂肪と筋肉間脂肪,また皮下脂肪と筋肉内脂肪が類似していた.すなわち,前者は後者に比較して,C46,C48よびC50 TGが少なく,C52よびC54 TGが多かった.TGの立体特異的脂肪酸分布はsn-2位に最も不飽和脂脂酸とくにオレイン酸含量が高く,飽和脂肪酸とくにステアリン酸の含量が低かった.sn-3位にはsn-1位に比較してステアリン酸含量が高い.一方,立体特異的脂肪酸分布から,1-ランダム,2-ランダム,3-ランダム配列を仮定して算出されるTGの分子量分布は,GCによって得られた分析値と異なっており,C52TG含量の計算値は分析値に比較して高く,C54 TGの含量は計算値が低いことが明らかとなった.

SummaryBackground and aimsTransthoracic esophagectomy using 3-field lymphadenectomy (TTE-3FL) for esophageal cancer is one of the most aggressive gastrointestinal surgeries. Early enteral nutrition (EN) for TTE-3FL patients is useful and valid for early recovery; however, EN using a fat-containing formula risks inducing chyle leak. In the present study, we retrospectively examined esophageal cancer patients treated byTTE-3FL and administered postoperative EN to elucidate the validity of lowering the fat levels in elemental formulas to prevent postoperative chyle leak and improve postoperative recovery.MethodsA total of 74 patients who received TTE-3FL for esophageal cancer were retrospectively examined. Patients were classified into two groups according to the type of postoperative EN: Group LF patients received a low-fat elemental formula, and Group F patients received a standard fat-containing polymeric formula. The following clinical factors were compared between the groups: EN start day, maximum EN calories administered, duration of respirator use, length of ICU stay, incidence of postoperative infectious complications, use of parenteral nutrition (PN), and incidence of postoperative chyle leak.ResultsPatients in Group LF were started on EN significantly earlier after surgery and they consumed significantly higher maximum EN calories compared to Group F patients (P

Samples of neutral lipid were taken from the carcasses of forty-eight Japanese Black steers, the progeny from three breeding bulls, on similar planes of nutrition and of the same age, and were analysed for fatty acid composition. The breeding bull seems to significantly affect the fatty acid composition of the lipid from the thoracic subcutaneous fatty tissue and the inter- and intra-muscular fatty tissues of the Longissimus dorsi muscle. No significant correlation between breeding bull and fatty acid composition of perinephric fatty tissue was found. There was an increase in total concentration of unsaturated fatty acids from internal to external sample locations.