Towards a unified model of neutrino-nucleus reactions for neutrino oscillation experiments.

A precise description of neutrino-nucleus reactions will play a key role in addressing fundamental questions such as the leptonic CP violation and the neutrino mass hierarchy through analyzing data from next-generation neutrino oscillation experiments. The neutrino energy relevant to the neutrino-nucleus reactions spans a broad range and, accordingly, the dominant reaction mechanism varies across the energy region from quasi-elastic scattering through nucleon resonance excitations to deep inelastic scattering. This corresponds to transitions of the effective degree of freedom for theoretical description from nucleons through meson-baryon to quarks. The main purpose of this review is to report our recent efforts towards a unified description of the neutrino-nucleus reactions over the wide energy range; recent overall progress in the field is also sketched. Starting with an overview of the current status of neutrino-nucleus scattering experiments, we formulate the cross section to be commonly used for the reactions over all the energy regions. A description of the neutrino-nucleon reactions follows and, in particular, a dynamical coupled-channels model for meson productions in and beyond the [Formula: see text](1232) region is discussed in detail. We then discuss the neutrino-nucleus reactions, putting emphasis on our theoretical approaches. We start the discussion with electroweak processes in few-nucleon systems studied with the correlated Gaussian method. Then we describe quasi-elastic scattering with nuclear spectral functions, and meson productions with a [Formula: see text]-hole model. Nuclear modifications of the parton distribution functions determined through a global analysis are also discussed. Finally, we discuss issues to be addressed for future developments.

CT and MR cholangiography: advantages and pitfalls in perioperative evaluation of biliary tree.

Recent developments in imaging technology have enabled CT and MR cholangiopancreatography (MRCP) to provide minimally invasive alternatives to endoscopic retrograde cholangiopancreatography for the pre- and post-operative assessment of biliary disease. This article describes anatomical variants of the biliary tree with surgical significance, followed by comparison of CT and MR cholangiographies. Drip infusion cholangiography with CT (DIC-CT) enables high-resolution three-dimensional anatomical representation of very small bile ducts (e.g. aberrant branches, the caudate branch and the cystic duct), which are potential causes of surgical complications. The disadvantages of DIC-CT include the possibility of adverse reactions to biliary contrast media and insufficient depiction of bile ducts caused by liver dysfunction or obstructive jaundice. Conventional MRCP is a standard, non-invasive method for evaluating the biliary tree. MRCP provides useful information, especially regarding the extrahepatic bile ducts and dilated intrahepatic bile ducts. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced MRCP may facilitate the evaluation of biliary structure and excretory function. Understanding the characteristics of each type of cholangiography is important to ensure sufficient perioperative evaluation of the biliary system.

Stimulation effect of galanin-like peptide (GALP) on luteinizing hormone-releasing hormone-mediated luteinizing hormone (LH) secretion in male rats.

Galanin-like peptide (GALP) is a recently isolated hypothalamic peptide which has sequence homology to galanin and binds to galanin receptors with high affinity. It has been shown that GALP neurons are localized in the arcuate nucleus and that GALP-immunoreactive fibers are in close apposition with LHRH neurons in the medial preoptic area (MPA). In the present study, we found that intracerebroventricular (icv) administration of GALP increased the plasma LH level but did not change the levels of other hormones. Concomitantly, accumulation of c-Fos protein was dramatically increased in the nuclei of LHRH-positive cells in the MPA by icv GALP administration. Furthermore, the GALP-induced plasma LH response was completely abolished by pretreatment with Cetrorelix, a LHRH receptor antagonist. On the other hand, GALP did not affect the release of LH, FSH, TSH, ACTH, GH or PRL directly from dispersed rat pituitary cells in vitro. These results strongly suggest a role for GALP in the control of gonadotropin secretion through a hypothalamic mechanism involving the release of LHRH.

Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor.

Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene, that suppresses metastases of human melanomas and breast carcinomas without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1, 4) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named 'metastin'. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo. The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.

Distribution of galanin-like peptide in the rat brain.

Galanin-like peptide (GALP) is a novel galanin-like peptide isolated from the porcine hypothalamus. To determine the distribution of GALP in the rat brain, we performed immunohistochemical studies using a monoclonal antibody toward the N-terminal sequence of GALP. GALP-immunoreactive neuronal cell bodies were observed only in the arcuate nucleus (Arc), which was further confirmed by in situ hybridization studies using digoxigenin-labeled antisense GALP riboprobe. Additional immunostained cells were found in the median eminence and infundibular stalk. The GALP neurons found in the Arc were further characterized by double label immunohistochemistry. More than 85% of the GALP neurons were immunostained with leptin receptor antibody. However, the GALP neurons and fibers found in the Arc were not labeled with alpha-MSH, somatostatin, neuropeptide Y, agouti-related protein, or galanin antibodies, indicating that GALP is found in neurons other than these known Arc neurons. Dense staining of GALP-containing fibers was found in the anterior parvicellular part of the paraventricular hypothalamic nucleus, in the ventral part of the lateral septal nucleus, and in the bed nucleus of the stria terminalis. Relatively dense staining was noted in the medial preoptic area (MPA), and weak staining was noted in the periventricular hypothalamic nucleus. Detailed double labeling studies in the paraventricular hypothalamic nucleus demonstrated that GALP-containing fibers converged in a more rostral direction than did agouti-related protein-containing fibers. Furthermore, GALP-immunoreactive fibers were in close apposition with GnRH-immunoreactive fibers in the MPA and bed nucleus of the stria terminalis, and about 6% of GnRH-positive neurons in the MPA showed close contact with the GALP-immunoreactive fibers. Our findings indicate that GALP neurons, as leptin-responsive neurons, may participate in the regulation of feeding behavior and/or reproductive functions.

Isolation and cDNA cloning of a novel galanin-like peptide (GALP) from porcine hypothalamus.

Galanin is a widely distributed neuropeptide with a variety of physiological functions. Three galanin receptor subtypes, GALR1, GALR2, and GALR3, have been reported. We isolated a novel galanin-like peptide (GALP) from porcine hypothalamus by observing its activity for increasing [(35)S]GTPgammaS binding to a membrane preparation of GALR2-transfected cells. The peptide had 60 amino acid residues and a non-amidated C terminus. The amino acid sequence of GALP-(9-21) was completely identical to that of galanin-(1-13). A cloned porcine GALP cDNA indicated that GALP was processed from a 120-amino acid GALP precursor protein. The structures of rat and human GALP-(1-60) were deduced from cloned cDNA, which indicated that the amino acid sequences 1-24 and 41-53 were highly conserved between humans, rats, and pigs. Receptor binding studies revealed that porcine GALP-(1-60) had a high affinity for the GALR2 receptor (IC(50) = 0.24 nM) and a lower affinity for the GALR1 receptor (IC(50) = 4.3 nM). In contrast, galanin showed high affinity for the GALR1 (IC(50) = 0.097 nM) and GALR2 receptors (IC(50) = 0.48 nM). GALP is therefore an endogenous ligand that preferentially binds the GALR2 receptor, whereas galanin is relatively non-selective.

Sequence and organization of pXO1, the large Bacillus anthracis plasmid harboring the anthrax toxin genes.

The Bacillus anthracis Sterne plasmid pXO1 was sequenced by random, "shotgun" cloning. A circular sequence of 181,654 bp was generated. One hundred forty-three open reading frames (ORFs) were predicted using GeneMark and GeneMark.hmm, comprising only 61% (110,817 bp) of the pXO1 DNA sequence. The overall guanine-plus-cytosine content of the plasmid is 32.5%. The most recognizable feature of the plasmid is a "pathogenicity island," defined by a 44.8-kb region that is bordered by inverted IS1627 elements at each end. This region contains the three toxin genes (cya, lef, and pagA), regulatory elements controlling the toxin genes, three germination response genes, and 19 additional ORFs. Nearly 70% of the ORFs on pXO1 do not have significant similarity to sequences available in open databases. Absent from the pXO1 sequence are homologs to genes that are typically required to drive theta replication and to maintain stability of large plasmids in Bacillus spp. Among the ORFs with a high degree of similarity to known sequences are a collection of putative transposases, resolvases, and integrases, suggesting an evolution involving lateral movement of DNA among species. Among the remaining ORFs, there are three sequences that may encode enzymes responsible for the synthesis of a polysaccharide capsule usually associated with serotype-specific virulent streptococci.

Sequence, assembly and analysis of pX01 and pX02.

Bacillus anthracis plasmids pX01 and pX02, harboured by the Sterne and Pasteur strains, respectively, have been sequenced by random 'shotgun' cloning and high throughout sequence analysis. These sequences have been assembled (Sequencher) to generate a circulate pX01 plasmid containing 181 656 bp and a single linear (gapped) pX02 contig containing at least 93.479 bp. Initial annotation suggests that the two plasmids combined contain at least 200 potential open reading frames (ORFs) with < 40% having significant similarity to sequences registered in open databases. Collectively, only 118 566 bp of the pX01 DNA (65%) represent predicted coding regions. This value is similar to published gene densities for other plasmids and is indicative of the larger intergenic spaces in plasmids vs those found in the chromosomes of the parental microbes (85-93% gene density). A 70 kbp region including the toxin genes (cya, lef and pag) is distinct from the remainder of the pX01 sequence: (1) it has a lower gene density (58 vs 70%) than the remaining 111 kbp; (2) it contains all but one of the co-regulated transcriptional fusions identified by transposon mutagenesis (Hoffmaster & Koehler 1997) and (3) it contains a significantly higher proportion of positive BLAST scores (62 vs 20%) for putative ORFs. These data suggest different origins for the two regions of pX01.

Requirement for the kinase activity of human DNA-dependent protein kinase catalytic subunit in DNA strand break rejoining.

The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is an enormous, 470-kDa protein serine/threonine kinase that has homology with members of the phosphatidylinositol (PI) 3-kinase superfamily. This protein contributes to the repair of DNA double-strand breaks (DSBs) by assembling broken ends of DNA molecules in combination with the DNA-binding factors Ku70 and Ku80. It may also serve as a molecular scaffold for recruiting DNA repair factors to DNA strand breaks. This study attempts to better define the role of protein kinase activity in the repair of DNA DSBs. We constructed a contiguous 14-kb human DNA-PKcs cDNA and demonstrated that it can complement the DNA DSB repair defects of two mutant cell lines known to be deficient in DNA-PKcs (M059J and V3). We then created deletion and site-directed mutations within the conserved PI 3-kinase domain of the DNA-PKcs gene to test the importance of protein kinase activity for DSB rejoining. These DNA-PKcs mutant constructs are able to express the protein but fail to complement the DNA DSB or V(D)J recombination defects of DNA-PKcs mutant cells. These results indicate that the protein kinase activity of DNA-PKcs is essential for the rejoining of DNA DSBs in mammalian cells. We have also determined a model structure for the DNA-PKcs kinase domain based on comparisons to the crystallographic structure of a cyclic AMP-dependent protein kinase. This structure gives some insight into which amino acid residues are crucial for the kinase activity in DNA-PKcs.

Comparison of adenosine triphosphate and dipyridamole in diagnosis by thallium-201 myocardial scintigraphy.

UNLABELLED: We examined whether 201Tl myocardial scintigraphy with intravenous infusion of adenosine triphosphate (ATP) can be substituted for dipyridamole (DIP) in the diagnosis of coronary artery disease CAD). METHODS: The coronary flow reserve (CFR) during intravenous infusion of ATP (0.10-0.20 mg/kg/min) was compared with that during intravenous infusion of DIP (0.56 mg/kg) using a Doppler flow wire in 19 subjects with normal coronary arteries. The highest CFR level was found in the ATP dose range of 0.16-0.20 mg/kg/min. The CFR at the ATP dose of 0.16 mg/kg/min was significantly higher than that during DIP infusion (4.2 versus 3.6) (p < 0.01), for which reason we adopted this dose of ATP. According, 201Tl SPECT in 140 patients with suspected CAD was performed after infusion of 0.16 mg/kg/min of ATP in 70 of them and 0.56 mg/kg of DIP in the 70 others. RESULTS: ATP stress 201Tl SPECT showed no significant difference in sensitivity and accuracy from DIP stress 201Tl SPECT (87.0% versus 82.9, and 87.1% versus 78.6, respectively). Adverse effects occurred at higher frequency when ATP was used, but they were mild and disappeared rapidly after administration was stopped. CONCLUSION: ATP stress 201Tl SPECT is accurate and safe. The optimal ATP regimen for this purpose is considered to be a 5-min infusion at 0.16 mg/kg/min. However, our data in CAD patients suggest that ATP stress 201Tl SPECT is equivalent to DIP stress 201Tl SPECT in the detection of CAD.

Detection of telomerase activity in prostate cancer by needle biopsy.

OBJECTIVES: Re-expression of telomerase is believed to play an important role in immortalization and carcinogenesis. Thus, telomerase activity is considered to be a potentially useful diagnostic marker. We evaluated the potential diagnostic use of assaying telomerase activity in needle biopsy samples of prostate. METHODS: 114 were obtained from 38 patients with suspected cancer who underwent transrectal ultrasound-guided systematic prostate needle biopsy. Two samples were obtained per site for histological examination and telomerase assay. The activity was assayed using the telomeric repeat amplification protocol and correlated with histological findings. RESULTS: Of the total of 114 samples, 57 were obtained from 22 prostate cancer patients. Telomerase activity was detected in 66% (25/38) of the samples which were histologically confirmed to contain cancerous cells and in 11% (2/19) of the samples from adjacent noncancerous tissues. Of 22 patients with prostate cancer, 82% were positive for telomerase activity in one or more samples by needle biopsy, whereas 1 of 16 patients without histologically cancerous tissues was positive for the telomerase. CONCLUSIONS: The results indicate that telomerase activity in needle biopsy samples is a useful diagnostic marker of prostate cancer.

[Usefulness of 123I-BMIPP myocardial scintigraphy for evaluation of the left ventricular function in patients with chronic heart failure].

We examined the relationship between free fatty acid metabolism using 123I beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) and cardiac function in patients with chronic heart failure (CHF). Cardiac free fatty acid metabolism was evaluated by the heart to mediastinum ratio (H/M), the heart to lung ratio (H/Lu), the heart to liver ratio (H/Li) and the myocardial uptake ratio (MUR) obtained from the planar imaging. Cardiac function was evaluated by the percent of fractional shortening (%FS) and the amount of left ventricular mass (LV mass) calculated with echocardiography. The study included 34 male and 14 female subjects of CHF with mean age of 61 +/- 9 years; dilated cardiomyopathy (DCM): n = 17, ischemic heart disease (IHD): n = 16, valvular disease: n = 5, hypertrophic cardiomyopathy: n = 4, hypertension: n = 4, amyloidosis: n = 2. The correlations between indices of BMIPP uptake and those of echocardiography were as follows: H/M vs. %FS (r = 0.67, p < 0.01), H/Lu vs. %FS (r = 0.49, p < 0.01), H/Li vs. %FS (r = 0.12, p = 0.42), MUR vs. %FS (r = 0.03, p = 0.86) and MUR/LV mass vs. %FS (r = 0.59, p < 0.01). The correlation coefficient between H/M and MUR/LV mass in patients with IHD was higher than that in patients with DCM. In conclusion, BMIPP, in particular, is a useful tool for evaluating cardiac function in patients with CHF.

[99mTc-MIBI myocardial tomography with intravenous infusion of adenosine triphosphate in the diagnosis of coronary artery disease].

To evaluate its feasibility, safety and diagnostic accuracy, 99mTc-MIBI myocardial tomography with adenosine triphosphate (ATP) infusion (0.16 mg/kg/min for 5 min) was performed 100 consecutive patients using the stress/rest one day protocol. None of the patients required treatment with aminophylline during the study. The sensitivity and specificity for detecting patients with coronary artery disease were 97% and 71%, respectively. Those for detecting individual coronary lesion (> or = 75% stenosis) were 92% and 89%, respectively. The high hepatic uptake of 99mTc-MIBI causes artifactual perfusion defects in the inferior myocardial wall, particularly on ATP stress images. In order to reduce this artifactual phenomenon, the interval time between injection and stress imaging must be increased.

Cosmids and transcribed sequences from chromosome 11q23.

To obtain cosmid markers and transcribed sequences from a specific chromosome region, a series of radiation-reduced hybrids (RHs) containing various regions of human chromosome 11 was prepared from microcell hybrid A9 (neo11) cells containing a normal human chromosome 11 tagged with pSV2neo at 11p11.2. Among 15 radiation hybrid clones isolated, RH(11)-9 which contains a q23 fragment in addition to the neo integration site, was used for the construction of a cosmid library. Cosmid clones having human DNA sequences were screened, and localized by Southern hybridization with the radiation hybrid panel. Fifty-nine cosmids were assigned to 11q23 and 6 cosmids to 11p11.2. Exon amplification proceeded with 23 of the 59 cosmids and 16 putative exons were cloned. Three of them were identical to those constituting a known gene which locates on q23 (ATDC), and the others were unknown. Thus, the RHs containing various subchromosomal fragments of chromosome 11 were useful for constructing region-specific DNA markers. The RH(11)-9 cells and putative exons also facilitate the positional cloning of genes in the 11q23 region.

Thallium-201 myocardial tomography with intravenous infusion of adenosine triphosphate in diagnosis of coronary artery disease.

OBJECTIVES: The purpose of this study was to evaluate the feasibility, safety and diagnostic accuracy of thallium-201 myocardial tomography with intravenous adenosine triphosphate (ATP) infusion in patients with suspected coronary artery disease. BACKGROUND: Both ATP and adenosine are potent coronary vasodilators with a very short half-life. Several studies have confirmed that the diagnostic accuracy of adenosine thallium-201 scintigraphy is comparable to that with exercise. However, a high incidence of side effects, including atrioventricular (AV) block, has also been reported. Because the appropriate infusion rate for ATP has not yet been determined, this agent has not been tested in combination with myocardial scintigraphy. METHODS: The study group included 253 consecutive patients who underwent thallium-201 myocardial tomography with ATP infusion (0.16 mg/kg body weight per min for 5 min). The occurrence of adverse effects was carefully monitored. Of the 120 patients with coronary angiography, 76 had significant coronary artery disease. Tomographic images were assessed visually and by computer-quantified polar maps, and they were compared with the results of coronary angiography. RESULTS: Although 56% of the patients had some adverse effects, they were transient and mild. In all patients, the ATP infusion protocol could be completed, and no patient required aminophylline; AV block occurred in only 2% of the patients. The sensitivity and specificity were 88% and 80%, respectively, by visual analysis and 91% and 86%, respectively, by computer quantification. CONCLUSIONS: Thallium tomography with ATP is feasible and has a diagnostic value similar to that with adenosine for detecting coronary artery disease. In addition, it may have fewer side effects than adenosine myocardial tomography.

Construction of 110 cosmid markers and a 4.5-Mb YAC contig on human chromosome 8p12-q11.

Microcell hybrids containing various regions of human chromosome 8 were formed by microcell-mediated transfer of neo-tagged chromosome 8 into the cells derived from severe combined immunodeficiency (SCID) mouse. Thus, 110 cosmid markers were isolated from SV40-transformed SCID fibroblast cell line (SCVA) containing a p12-q11.1 region of human chromosome 8 and were assigned to eight regions in 8p12-q11.1, using a microcell-hybrid panel. For positional cloning of a human gene that restores the DNA-repair defect in a mouse with SCID on 8p11.1-q11.1 (SCID region), we constructed a yeast artificial chromosome (YAC) contig of about 4.5 Mb. Overlapping YACs were further aligned by restriction mapping, using rare-cutting restriction endonucleases. The cosmids and YAC contig should facilitate isolation of the SCID gene and other genes, such as the Werner syndrome-responsible gene in or near this region.

Malignant lymphoma of the esophagus associated with macroglobulinemia: report of a case.

A case of non-Hodgkin's lymphoma of the esophagus in a 74 year old man is presented. Grossly, the surgically removed esophagus had a fusiform submucosal mass covered with smooth surfaced mucosa. Microscopic examination revealed that the mass consisted of a dense infiltrate of small to medium-sized lymphoid cells with plasmacytoid differentiation, leading to a diagnosis of diffuse small cell lymphoma with lymphoplasmacytic subtype. Laboratory data as well as immunohistochemical studies proved that the lymphoma produced monoclonal immunoglobulin M, giving rise to macroglobulinemia.

[Assessment of myocardial viability by thallium-201 reinjection imaging with sublingual nitroglycerin].

Although thallium-201 (201Tl) reinjection imaging improves the detection of myocardial viability compared to standard 3-4-hr redistribution (RD) imaging, it still underestimates the extent of viable myocardium. We examined whether 201Tl reinjection SPECT with sublingual nitroglycerin (NTG) had a higher sensitivity for viability detection than reinjection alone. Eighty patients with coronary artery disease were studied, 38 of them with an old myocardial infarction. At the peak of exercise, 111 MBq 201Tl was injected and the initial and the delayed SPECT images were obtained. Then, all patients were divided randomly into two groups, and in each group, SPECT data were obtained again after the injection of 37 MBq 201Tl with (NTG(+) group) or without 0.6 mg of sublingual NTG (NTG(-) group). Among 50 segments showing fixed defects on the delayed image in the NTG(+) group, 21 (42%) were found to be reversible on the reinjection image, as compared to 16 of 51 (31%) in the NTG(-) group. Twenty-two of 44 (50%) segments showing incomplete RD were found to be reversible in the NTG(+) group, while 17 of 42 (41%) segments in the NTG(-) group. Moreover, the ratio of reversible segments seen in the reinjection images was significantly higher in the collateralized regions of the NTG(+) group than in those of the NTG(-) group (20/26 vs. 14/28, p < 0.05). Thus, 201Tl reinjection SPECT with sublingual NTG improves the detection of ischemic but viable myocardium as compared to SPECT with reinjection alone.