Background Water avoidance stress (WAS) is reported to induce functional changes in visceral sensory function in rodents, but the results which have been demonstrated so far are not consistent, i.e., hypersensitivity or hyposensitivity. We determined the effect of WAS on visceral sensation and evaluated the mechanisms of the action. Methods Visceral sensation was assessed by abdominal muscle contractions induced by colonic balloon distention, i.e., visceromotor response (VMR), measured electrophysiologically in conscious rats. The electromyogram electrodes were acutely implanted under anesthesia on the day of the experiment. The threshold of VMR was measured before and after WAS for 1 h. To explore the mecha-nisms of WAS-induced response, drugs were administered 10 min prior to the initiation of WAS. Key Results WAS significantly increased the threshold of VMR, and this effect was no longer detected at 24 h after. Intraperitoneal injection of astressin(2)-B (200 mu g/kg), a corticotropin releasing factor (CRF) receptor type 2 antagonist abolished the response by WAS. Subcutaneous (sc) injection of sulpiride (200 mg/kg), a dopamine D2 receptor antagonist blocked the response, while sc domperidone (10 mg/kg), a peripheral dopamine D2 receptor antagonist did not alter it. Naloxone (1 mg/kg, sc), an opioid antagonist did not modify it either. Conclusions & Inferences WAS induced visceral hyposensitivity through peripheral CRF receptor type 2 and central dopamine D2 receptor, but not through opioid pathways. As altered pain inhibitory system was reported to be observed in the patients with irritable bowel syndrome, CRF and dopamine signaling might contribute to the pathophysiology.

Background Peripheral corticotrophin-releasing factor (CRF) plays an important role in stress-induced alterations of gastrointestinal motility. CRF injected peripherally inhibits gastric emptying, but its effect on gastric contractions has not been clarified in freely moving conscious rats. Methods Intraluminal gastric pressure waves were measured in freely moving conscious non-fasted rats using the perfused manometric method. We assessed the area under the manometric trace as the motor index (MI), and compared this result with those obtained 1 h before and after drug administration. Key Results Subcutaneous injection (sc) of CRF (15 mu g kg(-1)) increased the MI significantly. Pretreatment with intravenous astressin (100 mu g kg(-1)), a non-selective CRF antagonist, blocked the sc CRF (15 mu g kg(-1))-induced response, but astressin(2)-B (200 mu g kg(-1), sc), a selective CRF receptor type 2 (CRF2) antagonist, enhanced the CRF-induced increase in MI significantly. Meanwhile urocortin 2 (15 mu g kg(-1), sc), a selective CRF2 agonist, did not alter the basal MI, but it inhibited the sc CRF (15 mu g kg(-1))induced stimulation of gastric contractions. The intraperitoneal injection of cortagine (30 mu g kg(-1)), a selective CRF receptor type 1 (CRF1) agonist, mimicked the response induced by sc CRF. Conclusions & Inferences Peripheral CRF stimulates gastric contractions through CRF1. CRF2 activation inhibits the response induced by CRF, suggesting that CRF2 may have a modulatory action to CRF1 signaling in gastric motor activity.

Pedunculopontine tegmental nucleus (PPN) contributes to the control muscle tone by modulating the activities of pontomedullary reticulospinal systems during wakefulness and rapid eye movement (REM) sleep. The PPN receives GABAergic projection from the substantia nigra pars reticulata (SNr), an output nucleus of the basal ganglia. Here we examined how GABAergic SNr-PPN projection controls the activity of the pontomedullary reticulospinal tract that constitutes muscle tone inhibitory system. Intracellular recording was made from 121 motoneurons in the lumbosacral segments in decerebrate cats (n=14). Short train pulses of stimuli (3 pulses with 5 ms intervals, 10-40 mA) applied to the PPN, where cholinergic neurons were densely distributed, evoked eye movements toward to the contralateral direction and bilaterally suppressed extensor muscle activities. The identical PPN stimulation induced IPSPs, which had a peak latency of 40-50 ms with a duration of 40-50 ms, in extensor and flexor motoneurons. The late-latency IPSPs were mediated by chloride ions. Microinjection of atropine sulfate (20 mM, 0.25 ml) into the pontine reticular formation (PRF) reduced the amplitude of the IPSPs. Although conditioning stimuli applied to the SNr (40-60 mA and 100 Hz) alone did not induce any postsynaptic effects on motoneurons, it reduced the amplitude of the PPN-induced IPSPs. Subsequent injection of bicuculline (5 mM, 0.25 ml) into the PPN blocked the SNr effects. Microinjections of NMDA (5 mM, 0.25 ml) and muscimol (5 mM, 0.25 ml) into the SNr reduced and increased the amplitude of the PPN-induced IPSPs, respectively. These results suggest that GABAergic basal ganglia output controls postural muscle tone by modulating the activity of cholinergic PPN neurons which activate the muscle tone inhibitory system. The SNr-PPN projection may contribute to not only control of muscle tone during movements in wakefulness but also modulation of muscular atonia of REM sleep. Dysfunction of the SNr-PPN projection may therefore be involved in sleep disturbances in basal ganglia disorders.

We investigated the effects of peripheral injection of sauvagine, a CRF2 > CRF1 receptor (corticotropin-releasing factor) agonist compared with CRF, on two sets of tonic colorectal distension (CRDs 30, 40, 50 mmHg, 3-min on/off)-induced visceromotor response (VMR) measured as area under the curve (AUC) of abdominal muscle contraction in conscious female rats. Sauvagine (10 or 20 μg/kg, s.c.) abolished the 226.7 ± 64.3% and 90.4 ± 38.1% increase in AUC to the 2nd CRD compared with the 1st CRD (performed 30 min before) in female Fisher and Sprague–Dawley (SD) rats, respectively. CRF had no effect while the CRF1 antagonist, antalarmin (20 mg/kg, s.c.), alone or with sauvagine, blocked the enhanced response to the 2nd CRD, performed 60 min after the 1st CRD, and reduced further the AUC by 33.5 ± 23.3% and 63.5 ± 7.2%, respectively in Fisher rats. These data suggest that peripheral CRF2 receptor activation exerts antinociceptive effects on CRD-induced visceral pain, whereas CRF1 contributes to visceral sensitization.

Urocortin, a new mammalian member of the corticotropin-releasing factor (CRF) family has been proposed to be the endogenous ligand for CRF receptor 2 (CRF-R2). We studied the influence of intravenous urocortin on gastric emptying and the role of CRF-R2 in peptide action and postoperative gastric ileus in conscious rats. The intravenous doses of rat CRF and rat urocortin producing 50% inhibition of gastric emptying were 2.5 and 1.1 μg/kg, respectively. At these intravenous doses, CRF and urocortin have their actions fully reversed by the CRF-R1/CRF-R2 antagonist astressin at antagonist/agonist ratios of 5:1 and 67:1, respectively. Astressin (12 μg/kg iv) completely prevented abdominal surgery-induced 54% inhibition of gastric emptying 3 h after surgery while having no effect on basal gastric emptying. The selective nonpeptide CRF-R1 antagonists antalarmin (20 mg/kg ip) and NBI-27914 (400 μg/kg iv) did not influence intravenous CRF-, urocortin- or surgery-induced gastric stasis. These results as well as earlier ones showing that α-helical CRF9—41(a CRF-R2 more selective antagonist) partly prevented postoperative ileus indicate that peripheral CRF-R2 may be primarily involved in intravenous urocortin-, CRF-, and abdominal surgery-induced gastric stasis.

Molecular weight averages of polystyrene (PS) samples (SRM 706, SRM 705a, and PS-1) were determined at 24 laboratories belonging to the section of special study on SEC, using two sets of PS calibration standards commercially available at Tosoh (TSK) and Showa Denko (Shodex) companies. The PS-1 sample was used in the last three round robin tests. The sample concentrations, injection volume and other experimental conditions were prescribed as at the 2nd round robin test. Two calibration curves were constructed using TSK standards and Shodex standards, respectively. Molecular weight averages of the three samples calculated using the Shodex calibration curve were 3 to 14% higher than those calculated using the TSK calibration curve, and the differences between two molecular weight averages calculated using the Shodex and TSK calibration curves were significant at the 1% significance level. This means that when the values of the molecular weight averages are reported, the reporter has to declare which PS calibration standards were employed.

The early experience is reported here of the use of Intra‐operative frozen‐section service by telepathology using the Integrated Service Digital Network (ISDN), a commercially available system that is being connected between the Department of Pathology of Tottori University and Matsue City Hospital, a distance of 30 km. The transfer rate is currently 64kbit/s. The frozen‐section service was conducted for a total of 117 tissue specimens (organs) from 100 patients between August 1993 and May 1995. The average time taken for examination of each specimen of frozen section was 13min, ranging between 2 and 42min. The average number of transmitted Images was 6.2. Six cases necessitated more than 11 transmitted Images to make a diagnosis, while 13 cases could be diagnosed from two images only. Correct and permissible diagnoses were obtained in 109 (93.2%) out of 117 specimens when comparing the telepathology diagnosis with that of direct microscopy. Improper or misdiag‐nosis was made for eight cases (specimens), which were misinterpreted as papillary carcinoma in Basedow's disease, adenoma and hyperplasia in two pheochromocytomas, solid‐tubular carcinoma in phyilodes tumor, mastopathy in invasive carcinoma, metastatic carcinoma in astrocytoma, follicular lymphoma in reactive hyperplasia, and lymphadenitis in follicular lymphoma. in retrospect, diagnosis of these cases should have been deferred. From the results, it was concluded that the Intraoperatlve frozen‐section service by telepathology may be a worthwhile substitute for hospitals with limited accessibility to local pathology service, in spite of pitfalls in some cases. Well prepared, high‐quality frozen sections, sufficient verbal communication with surgeons, and a rather conservative attitude on the part of a well‐trained pathologist seem to be the essential Ingredients for reaching an accurate decision when using telepathology.

A 68-year-old man with undifferentiated carcinoma occurring in the cardioesophageal junction accompanied by hypercalcemia is reported, The serum level of parathyroid hormone-related protein (PTHrP) was remarkably elevated, Serum calcium and PTHrP levels decreased following chemotherapy, but this amelioration was temporary, He died of hypercalcemia, On autopsy, a significant amount of immunoreactive PTHrP was detected in the tumor tissue extract, and the tumor cells were stained strongly positive for PTHrP by immunohistochemistry. This is the first case of undifferentiated carcinoma in the gastrointestinal tract which demonstrated hypercalcemia due to PTHrP produced by the malignant tumor.

We report the rare case of malignant intestinal schwannoma, not accompanied with von Recklinghausen's disease. The main tumor was located in the ileum with multiple small tumors observed on the peritoneum. Histologically the tumor was composed of spindle cells exhibiting a nuclear palisading formation and abnormal mitotic figures were observed. The tumor was immunohistochemically positive for S-100 protein, glial fibrillary acidic protein, vimentin and neuron-specific enolase, but negative for desmin. Electron microscopically the tumor cell exhibited morphological findings characteristic of schwann cell differentiation. On the basis of these results, the tumor was diagnosed as malignant schwannoma occurring in the ileum.