The NK1 receptor and its participation in the synergistic enhancement of corneal epithelial migration by substance P and insulin-like growth factor-1

1. We have previously shown that substance P (SP) and insulin-like growth factor-1 (IGF-1) act synergistically to enhance the migration of rabbit corneal epithelial cells in an organ culture model. The present study was designed to identify the epithelial cell SP receptor that participates in this synergistic effect.
2. Rabbit corneal blocks were incubated for 24 h, then the length of the path of epithelial migration was measured. Reagents tried in the TC-199 culture medium, in the presence or absence of IGF-1, were: SP, agonists of tachykinin receptors NK₁, NK₂ or NK₃ and antagonists of tachykinin receptors NK₁ or NK₂.
3. The binding characteristics of SP receptors were examined in rabbit cultured corneal epithelial cells by binding assays with [¹²⁵I]-SP in the presence or absence of excess unlabelled SP or ligands of NK₁, NK₂ or NK₃ receptors.
4. As was demonstrated previously, SP and IGF-1 stimulated epithelial migration when they were added to the culture medium together, but individually they had no effect. NK₁ agonists had the same synergistic effect with IGF-1 as did SP, but the NK₂ and NK₃ agonists did not. Furthermore, the NK₁ antagonist abolished the synergistic effect of SP and IGF-1, but the NK₂ antagonist had no effect.
5. SP bound specifically to rabbit cultured corneal epithelial cells. The binding affinity was 0.44 nM and there were 2.43×10⁴ binding sites per cell. The NK₁ ligand competed, in a dose-dependent fashion, with the binding of SP to corneal epithelial cells, but neither the NK₂ nor NK₃ ligand affected binding.
6. We conclude that the SP receptor in rabbit corneal epithelial cells is NK₁ and that this receptor participates in the synergistic enhancement of corneal epithelial migration by SP and IGF-1. The precise mechanism(s) of this interaction requires more study. These findings imply that both neural and humoral factors are essential for the maintenance and healing of corneal epithelium.

     

New oily agents for targeting chemoembolization for hepatocellular carcinoma

PURPOSE: The evaluation of new oily agents for targeting chemoembolization for hepatocellular carcinoma. METHODS: Five types of oily preparation were injected into the hepatic artery of 54 rabbits inoculated with VX2 carcinoma cells in order to evaluate (1) the safety of these preparations, (2) their histologic distribution and the amount of agents remaining at tumor sites, and (3) computed tomographic (CT) images obtained. Of these preparations, three were made by mixing non-iodinated poppy seed oil and a thickener and then adjusted to have a viscosity lower than, equal to, or higher than that of lipiodol. A fourth preparation was a mixture of lipiodol and a thickener with a higher viscosity than lipiodol alone, and the fifth preparation was lipiodol alone. RESULTS: (1) No injury to the hepatic parenchyma was observed hematologically or histologically. (2) With increase in the viscosity, a significantly larger amount of agent remained at the tumor site. No agent was present at normal sites 14 days after intraarterial injection, regardless of which preparation was given. (3) On CT scans following intraarterial injection, tumor cells were visibly deeply stained in the non-iodinated preparation groups, while the lipiodol groups were not evaluable because of excessively high attenuation. CONCLUSION: The non-iodinated oily preparations and highly viscous oily preparations developed in the present study were more useful than lipiodol for treatment of hepatic tumors.     

No survival benefit from combined pancreaticosplenectomy and total gastrectomy for gastric cancer

BACKGROUND: It remains unknown whether extended surgery improves the survival rate of patients with gastric cancer. This study was a review of combined pancreaticosplenectomy with total gastrectomy for gastric cancer. METHODS: The clinicopathological details of 190 patients who underwent combined pancreaticosplenectomy with total gastrectomy between 1969 and 1996 were compared retrospectively with those of 206 patients who underwent total gastrectomy with splenectomy alone. RESULTS: There was no statistical difference in the survival rate when pancreaticosplenectomy was added to total gastrectomy. The mortality rate was similar, but the morbidity rate was higher in patients who had pancreaticosplenectomy. Six patients who had direct pancreatic invasion and two thought to have involved lymph nodes along the splenic artery survived for more than 5 years after operation. In the latter group, the metastatic lymph nodes along the splenic artery could have been resected without pancreatectomy. CONCLUSION: Since a combined pancreaticosplenectomy adds no survival advantage to total gastrectomy for gastric cancer, this procedure should no longer be regarded as routine.     

3D-CT cystography of submucosal elevated lesion of the bladder: report of two cases

We report 2 cases of rare inflammatory disease of the bladder arising from the bladder submucosa: eosinophilic cystitis in a 33-year-old woman and inflammatory pseudotumor of the bladder in a 41-year-old man. 3D-CT cystography demonstrated submucosal tumorous lesions clearly and enabled the evaluation of mucosae of lesions especially showed the bridging fold-like appearance of the submucosal tumorous lesion in eosinophilic cystitis.     

Apoptotic cascade of neurons in the subcortical sensory relay nuclei following the neonatal infraorbital nerve transection

A terminal transferase-mediated dUTP nick end labeling (TUNEL) method was utilized for detection of neuronal death in the subcortical relay nuclei of the trigeminosensory system following the infraorbital nerve transection in newborn rats. At 18-24 h after injury, numerous TUNEL-positive profiles were found within the ventroposteromedial thalamic nucleus (VPM) contralateral to the injury, whereas the VPM on the ipsilateral side and of the age-matched normal control contained only a few profiles per section. Electron microscopy revealed that the TUNEL-positive profiles were apoptotic neurons. The ventral part of the ipsilateral brainstem sensory trigeminal nuclear complex (the nucleus principalis, and the subnuclei oralis and interpolaris) exhibited statistically significant 65-70% increase in number of apoptotic neurons compared to the contralateral side. Taken together with our previous study [T. Sugimoto, C. Xiao, H. Ichikawa, Neonatal primary neuronal death induced by capsaicin and axotomy involves an apoptotic mechanism, Brain Res. 807 (1998) 147-154], the present results demonstrated a cascade of apoptosis in the primary, secondary and tertiary order sensory neurons along the neuroaxis.     

The renal lesions that develop in neonatal mice during angiotensin inhibition mimic obstructive nephropathy

BACKGROUND: Inhibition of angiotensin action, pharmacologically or genetically, during the neonatal period leads to renal anomalies involving hypoplastic papilla and dilated calyx. Recently, we documented that angiotensinogen (Agt -/-) or angiotensin type 1 receptor nullizygotes (Agtr1 -/-) do not develop renal pelvis nor ureteral peristaltic movement, both of which are essential for isolating the kidney from the high downstream ureteral pressure. We therefore examined whether these renal anomalies could be characterized as "obstructive" nephropathy. METHODS: Agtr1 -/- neonatal mice were compared with wild-type neonates, the latter subjected to surgical complete unilateral ureteral ligation (UUO), by analyzing morphometrical, immunohistochemical, and molecular indices. Agtr1 -/- mice were also subjected to a complete UUO and were compared with wild-type UUO mice by quantitative analysis. To assess the function of the urinary tract, baseline pelvic and ureteral pressures were measured. RESULTS: The structural anomalies were qualitatively indistinguishable between the Agtr1 -/- without surgical obstruction versus the wild type with complete UUO. Thus, in both kidneys, the calyx was enlarged, whereas the papilla was atrophic; tubulointerstitial cells underwent proliferation and also apoptosis. Both were also characterized by interstitial macrophage infiltration and fibrosis, and within the local lesion, transforming growth factor-beta 1, platelet-derived growth factor-A and insulin-like growth factor-1 were up-regulated, whereas epidermal growth factor was down-regulated. Moreover, quantitative differences that exist between mutant kidneys without surgical obstruction and wild-type kidneys with surgical UUO were abolished when both underwent the same complete surgical UUO. The hydraulic baseline pressure was always lower in the pelvis than that in the ureter in the wild type, whereas this pressure gradient was reversed in the mutant. CONCLUSION: The abnormal kidney structure that develops in neonates during angiotensin inhibition is attributed largely to "functional obstruction" of the urinary tract caused by the defective development of peristaltic machinery.     

Total Esophagectomy versus Proximal Esophagectomy for Esophageal Cancer at the Cervicothoracic Junction

To investigate the adequate extent of esophagectomy and lymphadenectomy for an esophageal cancer localized at the cervicothoracic junction, the mortality and morbidity rates, survival rates, and patterns of recurrence were retrospectively analyzed in two groups—14 patients who underwent total esophagectomy with or without laryngectomy and 15 patients who underwent proximal esophagectomy with or without laryngectomy—at Kurume University Hospital from 1981 to 1996. Proximal esophagectomy with or without laryngectomy resulted in a lower hospital mortality rate and better overall survival for patients who underwent curative esophagectomy compared with total esophagectomy with or without laryngectomy. Multivariate analysis indicated that the extent of esophagectomy (total esophagectomy versus proximal esophagectomy) was not a prognostic factor. The incidence of recurrence was not different between the two groups. Lymph node metastasis or recurrence from such esophageal cancers was localized to the neck and upper mediastinum. For an esophageal cancer localized at the cervicothoracic junction, therefore, proximal esophagectomy with or without laryngectomy and with cervical and upper mediastinal lymphadenectomy could be better indicated for preselected patients.     

Evaluation of child-rearing environmental factors that affect the occurrence of sudden infant death syndrome: interview conducted by public health nurses]

PURPOSE: We examined the child-rearing environmental factors that affect the occurrence of sudden infant death syndrome (SIDS) by using a nation-wide survey. METHOD: Infants who died due to SIDS between January 1996 and June 1997 in Japan were identified from death certificates. Controls of the same sex, birthplace, and birth months as the corresponding SIDS were chosen from birth certificates. Interviews of both cases and controls were undergone in January and February 1998 by public health nurses. RESULTS: The following Child-rearing factors exhibited a significant relationship with the occurrence of SIDS: 1. Concerning the sleeping position, the prone position was associated with increased risk compared to the supine position, with an odds ratio of 3.02 (95% c.i. 2.07-4.65). 2. Regarding the feeding method, artificial feeding only demonstrated a higher risk than breast feeding only, with an odds ratio of 4.92 (95% c.i. 2.78-9.63). 3. With regard to smoking, infants with both parents who smoked exhibited a higher risk than infants where neither parents smoked, with an odds ratio of 3.50 (95% c.i. 1.74-8.32).     

Age-related stimulation by tetragastrin of gastric mucin biosynthesis in rat

The effects of tetragastrin on gastric mucin biosynthesis in middle-aged rats were compared with those in young rats. The incorporation of [3H]glucosamine and [35S]sulfate into mucin was stimulated by tetragastrin in cultured corpus mucosa from 7-week-old rats. In contrast, tetragastrin could not enhance mucin biosynthesis in stomachs from 52-week-old rats. The isosorbide dinitrate-induced stimulation of corpus mucin biosynthesis observed in middle-aged rats was essentially the same as that seen in young rats. Nitric oxide (NO) synthase activity of the corpus was significantly reduced in the middle-aged rats compared to the young rats. NO synthase-immunoreactivity was observed at surface mucous cells in the corpus mucosa of young, but not of middle-aged, rats. These results suggest that aging decreases the effect of gastrin on gastric mucin biosynthesis through the age-related loss of NO synthase function in the surface mucous cell layer of rat stomach.