Temperature-dependent prolactin secretion and reproductive biology of the newt Triturus carnifex Laur

The effects of temperature on pituitary prolactin (PRL) gene expression and peripheral levels were studied in both male and female newts obtained from wild conditions during reproductive (Experiment I) and nonreproductive (Experiment II) periods; moreover, changes in parameters related to reproductive function are also described. Male and female newts were taken from a pond in February (Experiment I, reproductive period) and maintained for 1 month in tanks at 4 and 18 degrees C. In male newts kept at 4 degrees C, increase of PRL mRNA in the pituitary and plasma PRL was found compared with that measured in those kept at 18 degrees C. The increase in PRL secretion was parallel to that of plasma androgens and related secondary sexual characteristics (SSC) in males and of plasma estradiol-17beta and vitellogenin in females. On the contrary, in nonreproductive newts (Experiment II), taken from the field in May, no significant changes in plasma PRL, androgens, and SSC were found in those maintained at low temperature (4 degrees C), whereas low temperature significantly increased PRL mRNA expression in the male pituitary and PRL mRNA plus plasma PRL levels in females. These findings suggest that low temperature regulates PRL secretion in this urodele species, showing a sex- and season-related control mechanism; moreover, low temperature failed to influence the reproductive biology of newts taken from the field in May, after naturally occurring reproduction during winter months.     

Morphological changes of colonic Dieulafoy’s lesion: a case that could be retrospectively reviewed in a patient without treatment

Colonic Dieulafoy’s lesion (DL) is an unusual cause of lower gastrointestinal hemorrhage. We herein report the first case of DL in which the morphological changes could be retrospectively reviewed by endoscopy. A 61-year-old female, who was taking anti-thrombotics including low-dose aspirin, was admitted to our department with acute onset massive flesh bleeding per rectum. Although an emergent colonoscopy was performed, no bleeding source could be detected other than multiple diverticula in the ascending colon. A second colonoscopy after 1½ months revealed a small reddish polypoid lesion at the opposite site of the ileocecal valve, but showed no active bleeding points. After another 2 weeks, she complained of rectal bleeding again. She immediately underwent a third colonoscopy that showed pulsatile bleeding from normal overlying mucosa without a mucosal defect at the same site at the opposite site of the ileocecal valve, consistent with the DL. The lesion was successfully managed by argon plasma coagulation therapy. When reviewing initial colonoscopic images retrospectively, a telangiectasia was observed at the same site. This retrospective evaluation by endoscopy showed that the shape of the DL is changeable over a short period. It has been reported that aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of diverticular bleeding. Therefore, endoscopists should pay close attention not only to diverticular bleeding, but also to the presence of DL when performing colonoscopy on patients with rectal bleeding and taking aspirin or NSAIDs.     

Usefulness of FDG-PET for the diagnosis of postoperative recurrence of lung cancer]

No standardized postoperative follow-up strategy has been established for lung cancer patients, although CT and tumor markers are often employed. We conducted a retrospective study evaluating fluoro-2-deoxyglucose positron emission tomography (FDG-PET) for the diagnosis of postoperative recurrence of lung cancer. We evaluated 28 patients with suspected postoperative recurrence of lung cancer, who underwent FDG-PET between July 2004 and November 2005. Of these, 15 showed positive PET finings. Recurrence of lung cancer cases confirmed in 14 of these and the remaining case showed a postoperative scar. Thirteen patients with no findings on PET scan have demonstrated no evidence of recurrence during follow-up periods between 10 to 23 months. The negative predictive value was therefore 100%. FDG-PET in addition to chest CT and tumor markers for the diagnosis of the postoperative recurrence of lung cancer is considered to be beneficial in terms of avoiding excessive radiation exposure and limiting medical costs, but further evaluation in more patients is necessary.     

An extra-adrenal abdominal pheochromocytoma causing ectopic ACTH syndrome

We report a 55-year-old woman with ectopic adrenocorticotropin (ACTH) secretion caused by extra-adrenal pheochromocytoma. The patient presented with a 6-month history of hypertension and diabetes mellitus. Her serum and urinary cortisol levels were extremely high and dexamethasone failed to suppress the cortisol secretion. Her plasma ACTH levels were also elevated (>300 pg/mL) and irresponsive to corticotropin-releasing hormone (CRH) or metyrapone administration. Gel filtration analysis of the patient's plasma detected the existence of large molecular weight ACTH being eluted with a major peak of authentic 1-39 ACTH. Abdominal computed tomographic scan and magnetic resonance imaging revealed a 5-cm paraganglioma located underneath the left kidney, in which (123)I-MIBG tracer specifically accumulated. Bilateral adrenal glands were diffusely enlarged. After surgical removal of the paraganglioma, the patient's clinical symptoms improved and biochemistry normalized including plasma ACTH, urinary free cortisol, and urinary catecholamines. Subsequent histologic evaluation of the transected paranglioma tissue revealed ACTH, synaptin, and chromogranin-A histologically immunostaining. Culture of primary cells collected from the resected paraganglioma demonstrated of in vitro production of ACTH, noradrenaline, and adrenaline. This is the first report of ectopic ACTH syndrome induced by an extra-adrenal abdominal paraganglioma.     

Adenosquamous pancreatic cancer producing parathyroid hormone-related protein

An autopsy case of adenosquamous pancreatic cancer in a 61-year-old male patient with an elevated serum level of parathyroid hormone-related protein (PTH-rP) is reported. He was admitted to our hospital with a 1-month-long history of abdominal discomfort and progressive abdominal fullness. A computed tomography (CT) scan of the abdomen showed a retroperitoneal mass, approximately 10cm in diameter, involving the pancreas, with round enhancement on contrast examination. Histological examination of a specimen taken by CT-guided needle biopsy suggested squamous cell carcinoma or transitional cell carcinoma. Laboratory data on admission revealed a high serum calcium level and high PTH-rP level. The calcium level initially responded to intravenous hydration, furosemide, calcitonin, and bisphosphonates, decreasing from 15.0 to 9.0mg/dl. However, the hypercalcemia recurred after 10 days. The patient developed carcinomatous peritonitis and acute renal failure, and died on the 25th hospital day. Autopsy revealed a mass in the pancreatic body to tail, invading the retroperitoneum, with progressive carcinomatous peritonitis. Histological examination of the mass revealed infiltrating carcinoma, showing squamous differentiation with focal intracytoplasmic lumina formation, consistent with pancreatic adenosquamous carcinoma. Immunohistological examination showed positive staining for PTH-rP. Adenosquamous carcinoma of the pancreas is relatively rare; only a few cases associated with hypercalcemia and for which PTH-rP has been identified as a causative factor have been reported. This is the first case in which immunohistochemistry proved localized PTH-rP in adenosquamous pancreatic cancer cells, associated with persistent hypercalcemia.     

In vivo evaluation of P-glycoprotein function at the blood-brain barrier in nonhuman primates using [11C]verapamil

P-glycoprotein (P-gp) is a major efflux transporter contributing to the efflux of a range of xenobiotic compounds at the blood-brain barrier (BBB). In the present study, we evaluated the P-gp function at the BBB using positron emission tomography (PET) in nonhuman primates. Serial brain PET scans were obtained in three rhesus monkeys after intravenous administration of [(11)C]verapamil under control and P-gp inhibition conditions ([PSC833 ([3'-keto-Me-Bmt(1)]-[Val(2)]-cyclosporin) 20 mg/kg/2 h]). The parent [(11)C]verapamil and its metabolites in plasma were determined by HPLC with a positron detector. The initial brain uptake clearance calculated from the integration plot was used for the quantitative analysis. After intravenous administration, [(11)C]verapamil was taken up rapidly into the brain (time to reach the peak, 0.58 min). The blood level of [(11)C]verapamil decreased rapidly, and it underwent metabolism with time. The inhibition of P-gp by PSC833 increased the brain uptake of [(11)C]verapamil 4.61-fold (0.141 versus 0.651 ml/g brain/min, p < 0.05). These results suggest that PET measurement with [(11)C]verapamil can be used for the evaluation of P-gp function at the BBB in the living brain.     

A novel amphibian hypothalamic neuropeptide: isolation, localization, and biological activity.

Neuropeptides similar to the molluscan cardioexcitatory Phe-Met-Arg-Phe-NH2 have been identified in several vertebrates and characterized by the RFa motif at their C terminus (RFa peptides). In this study, we sought to identify an amphibian hypothalamic RFa peptide that may regulate secretion of hormones by the anterior pituitary gland. An acid extract of bullfrog hypothalami was passed through C-18 reversed-phase cartridges, and then the retained material was subjected to HPLC, initially using a C-18 reversed-phase column. RFa immunoreactivity was measured in the eluted fractions by a dot immunoblot assay employing an antiserum raised against RFa. Immunoreactive fractions were subjected to further cation exchange and reversed-phase HPLC purification. The isolated peptide was a novel RFa peptide and shown to have the sequence Ser-Leu-Lys-Pro-Ala-Ala-Asn-Leu-Pro-Leu-Arg-Phe-NH2. The cell bodies and terminals containing this peptide were localized immunohistochemically in the suprachiasmatic nucleus and median eminence, respectively. This RFa peptide stimulated, in a dose-related way, the release of GH from cultured pituitary cells, its threshold concentration ranging between 10(-9) and 10(-8) M. This peptide did not have any appreciable effect on the secretion of PRL and gonadotropins. It was ascertained that the peptide was also effective in elevating the circulating GH level when administered systemically. Thus, the amphibian hypothalamus was revealed to contain a novel functional RFa peptide that stimulates GH release. This peptide was designated frog GH-releasing peptide.     

Diffusion-weighted imaging of retroperitoneal malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1.

We present the diffusion-weighted imaging (DWI) findings for a malignant peripheral nerve sheath tumor arising in a retroperitoneal plexiform neurofibroma in a patient with neurofibromatosis type 1. Signal intensity of the malignant area was high on DWI and low on the apparent diffusion coefficient map and differed from findings for the benign area. DWI enabled clear differentiation between malignant and benign areas of the tumor.     

Serological survey of avian H5N2-subtype influenza virus infections in human populations

To investigate the distribution of antibodies against H5N2 influenza virus in humans living in Ibaraki prefecture, Japan, 266 single serum samples were collected to perform serological tests. Results were compared to investigate the relationship between positive results and several factors. The number of positive serum neutralization antibody titers (≥40) against avian influenza virus A/H5N2 was significantly greater (P < 0.05) among poultry workers, in comparison to a Japanese healthy population. The geometric mean titers of serum neutralization antibody against A/H5N2 were significantly higher (P < 0.05) among Ibaraki inhabitants and poultry workers (P < 0.0001) when compared to a Japanese healthy population. Seropositivity against A/H5N2 virus was significantly (P < 0.05) associated with age (≥50 years old) in poultry workers. These results suggest that seropositivity against H5N2 virus in Ibaraki specimens is significantly higher than those of a Japanese healthy population and that the surveillance of avian influenza viruses is very important to evaluate the invasion or emergence of new pandemic influenza viruses from species other than humans.