Preclinical studies on [11C]MPDX for mapping adenosine A1 receptors by positron emission tomography

In previous in vivo studies with mice, rats and cats, we have demonstrated that [11C]MPDX ([1-methyl-11C]8-dicyclopropylmethyl-1-methyl-3-propylxanthine) is a potential radioligand for mapping adenosine A1 receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. The radiation absorbed-dose by [11C]MPDX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of MPDX were not found. The monkey brain was clearly visualized by PET with [11C]MPDX. We have concluded that [11C]MPDX is suitable for mapping adenosine A1 receptors in the human brain by PET.     

Intrapulmonary lymph nodes: thin-section CT features of 19 nodules

PURPOSE: The purpose of this study was to describe the thin-section CT features of intrapulmonary lymph nodes that accompanied primary or metastatic lung tumors. METHOD: A retrospective analysis of thin-section CT features was performed on 19 nodules in 16 patients with pathologically confirmed intrapulmonary lymph nodes that accompanied primary or metastatic lung tumors. RESULTS: Of the 16 patients, 13 had a solitary nodule and 3 had two nodules. All nodules were distributed in the middle lobe, lingula, or lower lobe. On thin-section CT images, the nodule was located abutting the visceral pleura (n = 10) or within 8 mm of the visceral pleura (n = 9). The thin-section CT findings showed that most of the nodules were well circumscribed (n = 18), homogeneous (n = 19), ovoid (n = 10), or round (n = 9) and smaller than 12 mm in maximal diameter. The surrounding lung field was normal (n = 16). CONCLUSION: Intrapulmonary lymph nodes are subpleural in the lower lung field. On thin-section CT, they are well circumscribed, homogeneous, round or ovoid, and smaller than 12 mm in maximal diameter. In the differential diagnosis of subpleural nodules located in the lower lung field, it should be kept in mind that they may be intrapulmonary lymph nodes even though the patient has malignancy.     

Plasma ghrelin and desacyl ghrelin concentrations in renal failure

Ghrelin is a novel hormone that possesses growth hormone (GH)-releasing, cardiovascular, and metabolic activities. Ghrelin is a unique acylated polypeptide, and the naked peptide, desacyl ghrelin, does not have the activity. This study examines plasma ghrelin concentrations in 41 patients with mild to severe renal diseases. Two kinds of radioimmunoassays were used: amino-terminal immunoreactivity represents ghrelin alone (N-IR), and carboxyl-terminal immunoreactivity corresponds to the sum of both ghrelin and desacyl ghrelin (C-IR). In all subjects, the plasma N-IR was much smaller than the C-IR, indicating that desacyl ghrelin predominates over ghrelin in the circulation. The plasma C-IR, but not N-IR, was significantly correlated with the serum creatinine level and was increased 2.8-fold in patients with end-stage renal disease compared with those in patients with normal renal function. The plasma GH concentration was significantly correlated with the plasma N-IR and the C-IR, as well as with the serum creatinine level. Bilateral nephrectomy in mice caused marked increase in the plasma C-IR without significant changes in the local C-IR and ghrelin mRNA level in the stomach, which is the main site of ghrelin production. These findings suggest that circulating ghrelin concentrations play a role in the regulation of blood GH concentrations and that the kidney is an important site for clearance and/or degradation of desacyl ghrelin. Furthermore, elevation of blood GH levels in renal failure seems to be caused by a mechanism other than alteration in the circulating ghrelin concentration.     

The relationship of the anterior drawer sign to the shape of the tibial plafond in chronic lateral instability of the ankle

To determine what factors correlate with values for tested anterior drawer (AD) sign, we investigated stress radiographs in 71 patients with severe chronic lateral instability of the ankle as well as 320 normal controls. We found no correlation between AD and talar tilt (TT), but measurement of the anterior tip ratio (ATR) (ATR=tanA x 100) demonstrated a link of ATR with AD (r=0.74, p<0.001). The posterior tip ratio (PTR) (PTR=tanP x 100) was not correlated with AD (r=0.34, p=0.16). The ankle mortise angle (AMA) (the anterior opening of the lateral ankle mortise) was also not correlated with AD (r=0.27, p=0.23). Investigation of 320 normal ankles revealed a mean ATR of 9.1%+/-1.4%. The ATR in patients was 7.6%+/-1.7%, significantly lower than in the control patients. The values in female patients with chronic lateral instabilities were significantly less than the values in the females in the control group. But values for male patients were not different from the control group. Thus the anterior tip of the lateral tibial plafond, as it affects the ATR, may influence instability in anterior drawer function, especially in female patients with chronic lateral ligamentous instability of the ankle.     

Change of barometric pressure influences low back pain in patients with vacuum phenomenon within lumbar intervertebral disc

The present study investigates whether changes in barometric pressure influence low back pain in patients with vacuum phenomenon within lumbar intervertebral discs. Twenty-four patients with low back pain were examined: 12 with vacuum phenomenon within the intervertebral discs (VP [+] group) and 12 without the vacuum phenomenon (VP [-] group). All patients consented to an evaluation of low back pain in a hyperbaric oxygen chamber. In the VP (+) group, low back pain became more severe in one patient when atmospheric pressure was elevated, and in eight patients when atmospheric pressure was decreased. In the VP (-) group, two patients experienced more severe low back pain when atmospheric pressure was decreased. Our study demonstrated that low back pain might be aggravated by atmosphere depression in patients with lumbar disease associated with the vacuum phenomenon.     

Diagnosis, assessment, and treatment of alcohol withdrawal syndrome]

Alcohol withdrawal syndrome is the one of the most critical status among alcohol related disorders. Early detection, diagnosis, and appropriate treatment of alcohol withdrawal syndrome are keys to a successful outcome. This article describes the concrete method of diagnosis, assessment, and treatment of alcohol withdrawal syndrome.     

Improved toxicogenomic screening for drug-induced phospholipidosis using a multiplexed quantitative gene expression ArrayPlate assay

We previously showed that a toxicogenomics analysis of drug-induced phospholipidosis enabled the identification of 12 specific gene markers and the establishment of an in vitro real-time PCR screening assay for the assessment of the phospholipidosis-inducing potential of compounds. The purpose of this study was to transfer our PCR-based assay into a 96-well microplate-based multiple mRNAs measuring assay (ArrayPlate™ assay) in order to increase throughput. Specifically, we determined the expression of the 12 marker genes using real-time PCR and ArrayPlate in human hepatoma HepG2 cells that were treated for 24 h with each of amiodarone and 80 proprietary compounds.

The following three performance criteria were satisfied in the ArrayPlate analysis: 1. Sensitivity—the expression of mRNA for all target genes was detected at quantifiable levels. 2. Repeatability—signal intensities and fold change values of each marker gene were highly repeatable. 3. Correlation—fold change values and their average values, which were used as indices of phospholipidosis induction potential, showed apparent correlation between the ArrayPlate and real-time PCR assays.

Thus, the in vitro screening assay for compound-induced phospholipidosis should be transferable from a PCR-based assay to the higher-throughput ArrayPlate-based method.     

Serum heat shock protein 70 levels and lung cancer risk: a case-control study nested in a large cohort study.

Chronic inflammation contributes to the process of carcinogenesis, but few epidemiologic studies have examined associations with risk of lung cancer. Relationships between lung cancer risk and serum levels of both heat shock protein 70 (Hsp70) and high-sensitivity C-reactive protein (hsCRP) were investigated in a case-control study nested in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. Serum samples and lifestyle information were collected at baseline from 39,242 men and women between 1988 and 1990. Of these, 240 deaths from lung cancer were identified through 1999, and 569 controls were matched for sex, age, and study area. Serum levels were measured in 189 cases and 377 controls for Hsp70 and in 209 cases and 425 controls for hsCRP. Odds ratios (95% confidence intervals) across quartiles, adjusted for confounding factors, including smoking habits, were 0.83 (0.44-1.58), 1.41 (0.77-2.60), and 1.84 (0.92-3.71) for Hsp70 (P(trend) = 0.042) and 1.13 (0.67-1.91), 0.66 (0.38-1.16), and 1.19 (0.70-2.02) for hsCRP (P(trend) = 0.941). In males, odds ratios (95% confidence intervals) across quartiles were 1.30 (0.59-2.84), 1.74 (0.83-3.67), and 2.49 (1.06-5.85) for Hsp70 (P(trend) = 0.029). High levels of serum Hsp70 might thus be associated with increased risk of lung cancer among Japanese males, although further studies are needed to clarify associations between chronic inflammation and lung cancer.     

Alcohol dehydrogenase 2 His47Arg polymorphism influences drinking habit independently of aldehyde dehydrogenase 2 Glu487Lys polymorphism: analysis of 2,299 Japanese subjects.

Although the functional effect of alcohol dehydrogenase 2 (ADH2) His(47)Arg polymorphism has been elucidated, its effect on habitual drinking remains unknown. Here, we conducted a cross-sectional study in 2,299 nonalcoholic Japanese subjects (989 men and 1,310 women). Drinking status, ethanol consumption, and physical reaction to one glass of beer were examined with regard to ADH2 and aldehyde dehydrogenase 2 (ALDH2) polymorphism. Strength of associations were assessed by age-, sex-, smoking status-, and genotype-adjusted odds ratios and their 95% confidence intervals. ADH2 His/Arg and Arg/Arg genotypes showed higher risk for habitual drinking. Among men, ALDH2 genotype- and confounder-adjusted odds ratios (95% confidence intervals) were 1.30 (0.89-1.89) and 3.16 (1.03-9.70), and this trend was significant (P = 0.024). A similar trend was observed among women. The combination genotypes of two polymorphisms revealed the clear effect of the ADH2 Arg allele among those with ALDH2 Glu/Lys in both sexes (P(trend) = 0.007 for men and 0.024 for women). Physical reactions, such as flushing and palpitation, were significantly less common in those with Arg/Arg compared with other ADH2 genotypes, and this was marked when combined with ALDH2 Glu/Lys. Heavy drinker status was also strongly associated with ADH2 Arg alleles. In conclusion, this study showed the strong effect of ADH2 His(47)Arg polymorphism on habitual drinking regardless of ALDH2 genotype.