Effects of peripheral administration of a Neuromedin U receptor 2-selective agonist on food intake and body weight in obese mice.

BACKGROUND: Neuromedin U (NMU) is a neuropeptide with various physiological functions, including regulation of smooth-muscle contraction, blood pressure, stress responses and feeding behaviors. NMU activates two distinct receptors, NMUR1 and NMUR2, which are predominantly expressed in peripheral tissues and the central nervous system (CNS), respectively. It is reported that the NMU signaling system regulates food intake (FI) and body weight (BW) via NMUR2, suggesting that an NMUR2 agonist exhibiting anorectic effects would be a potential therapy for obesity. METHODS: Antiobesity effects of NMUR2 activation were assessed using a recently developed, novel NMUR2-selective agonist, NMU-7005 (a polyethylene glycolated octapeptide). Here we assessed cumulative FI and BW loss after peripheral administration of NMU-7005 in NMUR2 knockout and diet-induced obese mice. To gain mechanistic insights, we performed immunohistochemical analysis of c-Fos-like protein expression in the brain. RESULTS: We found that NMU-7005 was a NMUR2-selective agonist with little activity toward NMUR1. The anorectic effect of NMU-7005 was completely abrogated in NMUR2 knockout mice. Repeated subcutaneous administration of NMU-7005 showed a potent antiobesity effect with FI inhibition (P<0.025) in diet-induced obese mice. NMU-7005 in combination with the glucagon-like peptide-1 receptor (GLP-1R) agonist liraglutide showed an additive antiobesity effect, suggesting that NMUR2-mediated anorectic action is different from that of GLP-1R agonists. NMU-7005 also elicited a minimal conditioned taste-aversive effect, while the effect of liraglutide was significant. As c-Fos expression was upregulated in the hypothalamus and the medulla oblongata in NMU-7005-administered mice, the pharmacological effects of NMU-7005 appeared to be mediated via activation of the CNS. CONCLUSION: Our results demonstrated that a novel NMUR2-selective agonist, NMU-7005, is a beneficial tool for the elucidation of NMUR2-mediated physiological functions, which is a promising therapeutic strategy for treating obesity.

[Pulmonary pleomorphic carcinoma; report of 2 cases].

The 1st case was a 74-year-old male diagnosed as femoral neck fracture. Biopsy of the bone revealed metastatic adenocarcinoma. Chest computed tomography (CT) showed a mass lesion located in the right lower lobe. With a diagnosis of primary lung cancer (cT2N1M1), two-staged operation was performed. Pathological diagnosis was pleomorphic carcinoma [pT2N1M1 (OSS), stage IV]. He died 8 months after surgery due to metastasis to the thoracic spine. The 2nd case was a 80-year-old female who complained of lateral chest pain. Chest CT revealed a tumor in the right hilar region, which was diagnosed as adenocarcinoma by transbronchial lung biopsy. Only thoracic drainage was performed since metastases to the brain and the rib were demonstrated. She died 2 months after admission. Autopsy revealed pleomorphic carcinoma of the lung with metastasis to the brain, costa and mediastinal lymph nodes.

Optical-damage-free guided second-harmonic generation in 1% MgO-doped stoichiometric lithium tantalate.

Room-temperature cw second-harmonic generation from telecom wavelengths, with 30% W(-1) cm(-2) efficiency and second-harmonic power levels up to 41 mW, was achieved in buried waveguides fabricated by reverse-proton exchange in 1% MgO-doped stoichiometric lithium tantalate without any evidence of optical damage. The technology proves suitable for the realization of efficient nonlinear frequency converters and all-optical devices.

Reverse-proton-exchange in stoichiometric lithium tantalate.

Buried waveguides with nearly symmetrical refractive index profile and high homogeneity were obtained by applying the reverse-proton-exchange technique to MgO doped stoichiometric lithium tantalate, a promising nonlinear material due to its low coercive field and high damage threshold. By characterizing several samples fabricated under different experimental conditions, we identified a fabrication procedure in which the annealing and the reverse-exchange processes are performed at the same temperature, and the diffusion of hydrogen ions towards the substrate is negligible during the burial step. These fabrication conditions are simpler than the conventional ones used for lithium niobate. Accurate empirical laws were found, relating the fabrication conditions to the optical parameters.

Natural history of sigmoid colon cancer: report of a patient observed for 4 years.

We report a case of sigmoid colon cancer that was left untreated for a period of 4 years, because the patient declined treatment. A 59-year-old man was found to have an early carcinoma of the sigmoid colon measuring approximately 12 mm in diameter. The lesion, initially a flat cancer, increased in height and became sessile 4 months later. Subsequently, the central portion of the lesion became ulcerated, leaving an elevated ring along its periphery. The lesion eventually evolved into an ulcerated, invasive cancer. This sequence has not been observed with colonoscopy before.

Quasinondestructive holographic recording in photochromic LiNbO3

We have observed quasinondestructive holographic storage with a continuous-wave laser at lambda = 532 nm in near-stoichiometric LiNbO3 doped with Tb and Fe. This crystal showed an exceptionally long grating decay time and also exhibited a fast color change upon exposure to ultraviolet (UV) light. It was demonstrated that the grating recorded from the UV-exposed, colored state can be continuously read out over 9 h at a reading intensity as high as 8 mW/cm(2). In addition, the written grating could be easily erased with UV illumination which returned the crystal back to the original colored state.

Angle-multiplexed hologram storage in LiNbO(3):Tb, Fe.

We have performed hologram multiplexing with a cw laser at lambda=532 nm in a near-stoichiometric LiNbO(3) :Tb, Fe crystal that exhibits a visible absorption band induced by UV light. When 50 plane-wave holograms were angle multiplexed from the UV preexposed state, the recording sensitivity gradually decreased, owing to bleaching of the induced absorption. However, a conventional recording schedule of multiplexing many holograms of equal diffraction efficiency can be used in this photochromic material. The gradual decrease in recording sensitivity throughout multiplexing can be compensated for by the increased erasure-time constants of later-written holograms. An M/# of 1.73 was obtained in a crystal of 3.3-mm thickness.

[A case of arteriovenous fistula of the lung].

A 29-year-old male was admitted to our hospital for further evaluation of left sided paresis, cyanosis, clubbing finger. The laboratory data revealed polycythemia and hypoxemia. Cerebralarteriogram showed right middle cerebral artery occulusion. Cardiofunctional test showed atrial fibrillation, lower left ventricular function. Cardiac catheterization, pulmonary arteriography and three dimensions CT were performed. Right to left shunt rate was 20.4%. A single large pulmonary arteriovenous fistura with a feeding artery (A10) and a draining vein (V10) was found clearly. In this cases, arteriovenous fistula was large, blood flow was thought to be rapid. We thought transcatheter embolization was not useful. And we performed right lower lobectomy. Postoperative course was not eventful. Cyanosis disappeared, clubbing finger was cured.

Stoichiometric Mg:LiNbO(3) as an effective material for nonlinear optics.

Photorefractive damage, optical absorption, photoconductivities, and photogalvanic currents of stoichiometric LiNbO(3) single crystals with different Mg doping levels have been investigated. Nominally pure stoichiometric LiNbO(3) shows lower photorefractive damage resistance than congruent crystal; however, stoichiometric crystals doped with MgO of more than 1.8 mol. % exhibit no measurable photorefractive damage at 532 nm to intensities of as much as 8 MW/cm(2) . This remarkable damage resistance can be attributed not only to increased photoconductivity but also to decreased photogalvanic current. Stoichiometric Mg:LiNbO(3) also demonstrates the shortest absorption edge, 302 nm, and a single-domain nature with low scattering losses.

Identification and characterization of a novel human cortistatin-like peptide.

Expressed sequence tags (ESTs) that showed significant homology to rat cortistatin (CST) were found in a human fetal brain cDNA library. A protein coded by the cDNA showed 55% identity to rat preprocortistatin in amino acid. Similarly in the generation of mature peptides from rat preprocortistatin, it was expected that cleavage at dibasic amino acids in the C-terminal portion of the coded protein might produce at least two different sizes of mature peptides with 29 and 17 amino acid residues, respectively. We chemically synthesized the predicted mature peptide with 17 amino acid residues (hCS-17) and examined its biological activities. It bound to all human somatostatin receptor (SSTR) subtypes in almost the same manner as rat CST-14. It also inhibited cAMP production induced by forskolin through SSTRs. Administration of hCS-17 to the cerebral ventricle showed flattening of cortical and hippocampal electroencephalograms in rats. These results indicate that a bioactive peptide encoded by the cDNA is a human counterpart corresponding to rat CST.

[Analysis of colonic motility by fast Fourier transform].

Colonic motility curve was continuously recorded in dog using a strain gauge force transducer and the curve was analyzed by fast Fourier transform. (1) The basic pattern of the colonic motility curve was a gradually increasing and decreasing contractile wave. (2) The frequency components of the basic contractile wave showed a trimodal distribution with peaks at around 1, 20 and 80 mHz. (3) The 1 mHz component showed a sine curve and represented the slow, big motion in the basic contractile wave. (4) The 20 mHz component represented the relatively rapid, gradually increasing and decreasing, big motion in the basic contractile wave. (5) The 80 mHz component represented the rapid, small motion in the basic contractile wave. (6) The fundamental frequency components of the colonic contractile wave were unchanged before and after defecation. (7) For the antiperistaltic wave which disappeared during transmission, the peaks of the wavelength components weakened during transmission and the wave progressed to a multi-modal curve. Our findings indicate that fast Fourier transform is an extremely useful method in elucidating colonic motility.

Combination therapy consisting of arterial infusion chemotherapy (EPF, EAP) and transcatheter arterial embolization (TAE).

From January 1988 to January 1993, 45 patients with unresectable advanced hepatocellular carcinoma (HCC) were treated with a new combination therapy consisting of arterial infusion chemotherapy and TAE. The combination therapy was performed according to our treatment schedule as follows: two courses of arterial infusion chemotherapy were given first, and then transcatheter arterial embolization (TAE) using a mixture of Lipiodol and cisplatin powder was performed. Two arterial infusion chemotherapeutic regimens were employed: EPF (etoposide, cisplatin, and 5-fluorouracil) and EAP (etoposide, Adriamycin or Epi-adriamycin, and cisplatin). The anticancer drugs were infused through a catheter inserted into the proper or common hepatic artery. Assessment was made of the anticancer effect and survival rate of each treatment method. The response to each therapy was evaluated on the basis of CT performed prior to and after the treatment. In the EPF.TAE group, the response rate was about 46%, whereas in the EAP.TAE group it was 48%. Overall, 21 of 45 patients attained a regression rate of 50% or more. Furthermore, daughter nodules decreased in size or disappeared in about 67% of 15 patients. Additionally, tumor thrombi tended to show a similar response. In all of the cases, the average duration of survival was 30.3 months, and the 1-year survival value was 68%, the 2-year survival value was 44%, and the 3-year survival value was 35%. These results were superior to those obtained with TAE therapy alone.

[Dynamic MR imaging of the pituitary gland by the fast spin echo (RARE) sequence].

The Fast Spin Echo (RARE: Rapid Acquisition with Relaxation enhancement) sequence for the dynamic MRI of the pituitary gland was performed in 18 patients suspected of the intracranial lesions. The SNR of the plain image of 5 pituitary glands was measured on the FSE 400 and 200/17/8/2 (TR/effective TE/echo train length/excitation) and the spin echo 100/11/2 (TR/TE/excitation) sequence. The FSE (TR = 400) provided the highest SNR than others, The FSE sequence was able to acquire increased spatial resolution and reduced acquisition time, and was the significant sequence for the dynamic MRI of the pituitary gland.

[Determination of potential doubling time using in vitro continuous labeling method with bromodeoxyuridine: estimation in head and neck squamous cell carcinoma].

Using in vitro continuous labeling with bromodeoxyuridine and immunohistochemical staining, potential doubling time (Tpot) was calculated in 24 patients with head and neck carcinoma treated with radiotherapy. There was no evident correlation between Tpot and tumor response in the cases treated with external irradiation. However, in one case of T2N0 mesopharyngeal carcinoma with short Tpot, tumor was microscopically residual even though it showed good radioresponsiveness during radiotherapeutic course. Meanwhile, all patients treated with brachytherapy showed complete response in spite of various Tpot. Tpot seems significant in the selection of fractionation to control head and neck carcinoma with external radiotherapy.

[Angiography in arteriosclerosis].

Advances in angiography of arteriosclerosis have been made possible by improvement of angiographic techniques, materials, such as narrow catheters and gliding guidewires, x-ray apparatus and equipments, including digital subtraction angiography (DSA), computed radiography and magnetic resonance angiography and contrast media. Improved, narrow and yet wide lumen catheters have made it possible to insert the catheter via the axillary or brachial artery. The matrix of DSA was increased to 1024 x 1024 from 512 x 512, and resolution of DSA has been greatly improved. Intravenous DSA has made examination of aneurysm or arterial stenosis or occlusion, easier without much harmful invasion. Ionic or non-ionic low osmolar contrast media has greatly reduced the irritation to the vessels.

[Percutaneous transluminal laser angioplasty].

Percutaneous transluminal laser angioplasty (PTLA) has been carried out on 63 peripheral arterial occlusive lesions in 43 patients. Most patients complained of intermittent claudication. The sites of lesions are the iliac artery (28 lesions or 44.4%), the femoropopliteal artery (30 lesions or 47.6%), and the below knee artery (5 lesions or 8.0%). There are 54 lesions (85.7%) that showed over 70% stenosis, with 19 of them complete occlusions (30.2%). Out of 63 lesions, 16 lesions or 25.4% had occlusions of over 10 cm. A Nd:YAG laser (1.06 microns, continuous wave) was used for the vaporization of atheromatous plaque and old thrombus. The laser was irradiated by increments of 1 to 2 seconds at 80W using the non-contact method, at 10-25W using the contact method with a ceramic tip and at 10-15W with a bare laser fiber. Balloon dilatation was then utilized. The initial success rate was 85.7%. The 5 year cumulative patency rate after PTLA is 88.4% in total cases, 88.7% in the iliac artery, 86.1% in the femoropopliteal artery, and 100% in the below knee artery. The 5 year cumulative patency rate for stenosis of the iliac artery is 91.0%, and it is 92% for stenosis of the femoropopliteal artery, and 81% for occlusion of the femoropopliteal artery. PTLA seems to have improved the cumulative patency rate when compared with that of conventional PTA.

Arterial infusion chemotherapy for advanced hepatocellular carcinoma using EPF and EAP therapies.

Arterial infusion chemotherapy of EPF (etoposide, cisplatin, and 5-fluorouracil) or EAP (etoposide, Adriamycin, and cisplatin) was carried out in 28 cases of advanced hepatocellular carcinoma (HCC) between January 1988 and December 1990, and assessment was made of the anticancer efficacy of each treatment method. In all, 13 patients were treated with EPF therapy and 15 received EAP therapy. The anticancer agents were infused through a catheter inserted into the proper or common hepatic artery. The catheter was inserted via the axillary artery or common femoral artery using Seldinger's method or the cut-down method. The results of each therapy were analyzed in relation to the tumor regression rate and the side effects encountered. The tumor regression rate was determined on the basis of two-dimensional evidence obtained by computed tomography performed before and after treatment. The treatment results were also compared with the results of chemoembolization therapy using a mixture of cisplatin (CDDP), Adriamycin (ADM) and lipiodol. Of the 28 patients treated with arterial infusion chemotherapy, 14 (50%) attained a regression rate of 50% (PR). In all, 46% of the EPF group and 53% of the EAP group achieved a PR. These results were superior to those obtained using chemoembolization therapy. In general, the side effects were relatively mild and transient.

Proteases involved in generation of beta- and alpha-amylases from a large amylase precursor in Bacillus polymyxa.

The genes for extracellular neutral protease (Npr) and intracellular serine protease (Isp) were cloned from Bacillus polymyxa in order to elucidate the process involved in the generation of multiple beta-amylases and an alpha-amylase from a large amylase precursor. The npr gene was composed of 1,770 bp and 570 amino acids, while the isp gene was composed of 978 bp and 326 amino acids. Both proteases produced by E. coli cleaved the amylase precursor to generate beta- and alpha-amylases. Furthermore, several other proteases produced the same products from the precursor. A 130-kDa amylase precursor has two large domain structures responsible for the generation of beta- and alpha-amylases. The junction region of approximately 200 amino acids may be exposed on the surface of the molecule and susceptible to proteolytic enzymes, which results in the formation of multiple amylases.