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.     

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.     

Analysis of the potentiating action of NG-nitro-l-arginine on the contraction of the dog temporal artery elicited by transmural stimulation of noradrenergic nerves

Summary Dog temporal artery strips without endothelium responded to transmural electrical stimulation with a contraction which was potentiated by N^G-nitro-l-arginine (l-NNA). The noradrenaline-induced contraction and the release of 3H-noradrenaline were not affected. The stimulation-induced contraction was reversed to a relaxation by phentolamine. The relaxation was not influenced by timolol and atropine but inhibited by l-NNA; l-arginine abolished the inhibition. Transmural stimulation released NO_x from the arteries, the release being abolished by l-NNA. Potentiation by l-NNA of the neurally-induced contraction appears to be due to elimination of NO produced by non-adrenergic, non-cholinergic vasodilator nerve activation. Send offprint requests to N. Toda at the above address     

Primary dermal and eye irritability tests of hydrophobically modified hydroxypropyl methylcellulose in rabbits.

Primary dermal and eye irritation tests of hydrophobically modified hydroxypropyl methylcellulose (HM-HPMC, hydroxypropyl methylcellulose modified with stearylglycidylether), a new cellulose derivative used as a thickener for topical pharmaceuticals and cosmetics, were conducted in rabbits. A dispersion of HM-HPMC (3%) was applied to intact and abraded skins and reactions were observed. A very slight erythema was observed in both skins and this polymer was categorized as a "mild irritant". In the eye irritation test, with a dispersion of the same concentration, it was categorized as "marginal" in unrinsed eyes and "negative" in rinsed eyes.     

Pterion and epipteric bones in Japanese adults and fetuses, with special reference to their formation and variations]

The formation and variations of the pterion and epipteric bones were examined in total of 614 Japanese skulls. The materials used consisted of 258 skulls of Japanese fetuses ranging from the fourth to the ninth month, 20 skulls of Japanese juveniles from the third month to 17 years of age, and 336 skulls of Japanese adults from 20 to 89 years of age. For the skulls examined the incidence of ossification in the fetal sphenoidal fontanelle was 3.6% on each side, whereas epipteric bones were observed in more than 10% of the juvenile and adult pteria. Great variation was seen in the form of the adult pterion. The most common form was a sphenoparietal contact in which the pteria were classified into usual (306 pteria), high (119), low (21), and narrow (32) types Another form of this type, a frontal process of the temporal bone without contact with frontal bone, was found in five pteria. The form of frontotemporal contact is classified into two types: One is with a frontal process of the temporal bone (17 pteria), and another is a K-shaped contact referred to as "stellate" (four). The two types were observable in adult skulls of all ages, although the fused pteria and fusing epipteric bones were most often seen in cases over 40 years of age. The results suggest that the pterion formation has two phases, the first occurring before the occlusion of sphenoidal fontanelle, and the second starting after 40 years of age.     

Twelve cases of jugular foramen neurinoma

Twelve patients with jugular foramen neurinoma were operated on at our clinic between 1974 and 1990. The initial signs and symptoms were variable; dysfunctions of the 7th, 8th, 9th, 10th, and 11th nerves were frequently observed. Among these, involvement of the eighth nerve was most frequent, and three patients were given a misdiagnosis of acoustic neurinoma. Computed tomography scan and magnetic resonance imaging were useful not only for the correct diagnosis, but also for planning the surgical treatment and postoperative followup. Surgical resection was accomplished with four different approaches: (1) suboccipital approach without opening the jugular foramen, (2) suboccipital approach with opening the jugular foramen, (3) suboccipital approach with opening the jugular foramen combined with infralabyrinthine approach, (4) infralabyrinthine approach. The surgical approach depended on the presence of intracranial tumor and on the extent of extracranial involvement. There was no operative mortality. Dysfunction of the 8th, 9th, 10th, or 11th nerve did not improve in any patient after tumor removal. In contrast, 12th nerve palsy improved in two of three patients after tumor removal. The nerve of origin was identified in five cases; those were from the ninth nerve in three and from the 11th nerve in two.     

Cell cycle specific fluctuations of adenosine 3',5' -monophosphate and prostaglandin binding in synchronized mastocytoma P-815 cells

Endogenous adenosine 3',5' -monophosphate (cAMP) levels in mastocytoma P-815 cells, synchronized either at the G1/S transition by amethopterin- or double thymidine-block or in mitosis by colcemid block, were highest during late S and early G2 phases and lowest during mitosis. These cell cycle-dependent changes in cAMP levels were largely accounted for by changes in adenylate cyclase and phosphodiesterase activities. Similar fluctuations occurred simultaneously with specific prostaglandin E1 (PGE1) binding, histidine decarboxylase activity, histamine content, and [35S]SO-2(4) incorporation into glycosaminoglycans of the cells. In addition, endogenous levels of the E group of prostaglandins (PGEs) and "14C]carachiodonic acid incorporations into PGE, phosphatidylcholine and phosphatidylinositol also exhibited fluctuation patterns similar to that of cAMP levels. Since cAMP levels still fluctuated in a serum-depleted medium where DNA synthesis and cell division were inhibited, endogeneous levels of prostaglandin and cAMP appeared not to be regulated solely by serum factor(s). Exposure of cells at G1/S transition to 1-methyl-3-isobutylxanthine (MIX) resulted in 10-fold elevation of cAMP levels throughout the cell cycle without affecting DNA synthesis. On the other hand, PGE1 and/or MIX added at late S phase elevated cAMP levels, prolonged C2 phase and retarded the cell division, but these agents added at the beginning of mitosis elevated cAMP levels without affecting the cell division. These results suggest that prostaglandin newly synthesized by the increased metabolism of phospholipids promote the cAMP synthesis via their binding to the receptors and thereby control the division and phenotypic expression of mastocytoma P-815 cells.