P16-immunostaining pattern as a predictive marker of lymph node metastasis and recurrence in early uterine cervical cancer.

OBJECTIVES: We investigated the relationship between P16-immunostaining patterns and clinicopathological factors in early uterine cervix cancers and assessed whether P16-immunostaining patterns predict the prognosis of the patients with early uterine cervix cancers. METHODS: Twenty-nine early squamous cell carcinoma (SCC) specimens of the uterus were examined using immunohistochemistry for P16 expression. The P16-immunostaining pattern was classified into two groups: the homogeneous type and the heterogeneous type. P16-immunostaining patterns were evaluated in different parts of the carcinoma in situ (CIS): the center of the tumor and the front interface of the infiltrating tumor. RESULTS: All specimens were of the homogeneous type in CIS. The P16-immunostaining pattern was significantly of the heterogeneous type in the front interface of the infiltrating tumor with lymphatic invasion, vascular invasion, lymph node metastasis, and recurrence. Regarding the P16-immunostaining patterns in the front interface of the infiltrating tumor, the patients with the heterogeneous type showed a significantly worse prognosis than the patients with the homogeneous type. CONCLUSIONS: The prognosis of patients with early uterine cervical SCC may be predicted by evaluating the P16-immunostaining pattern in the front interface of the infiltrating tumor.     

Intracerebroventricular injection of brain natriuretic peptide inhibits vasopressin secretion in conscious rats

The effect of intracerebroventricular (i.c.v.) injection of brain natriuretic peptide (BNP), a novel peptide purified from the porcine brain, on arginine vasopressin (AVP) secretion was studied in conscious, unrestrained rats and was compared with that of atrial natriuretic polypeptide (ANP). I.c.v. administration of BNP (0.01, 0.1 or 1 nmol) significantly inhibited basal AVP secretion and the effect of BNP was comparable to that of ANP. The AVP secretion induced by i.c.v. injection of angiotensin II (0.1 nmol) was significantly suppressed by the pretreatment with BNP (0.1 or 1 nmol). These results suggest that BNP is involved in the central control of AVP secretion either alone or in combination with brain ANP.     

Effects of hypoxia and tumor necrosis factor-alpha on production of plasminogen activator inhibitor-1 in human proximal renal tubular cells

Chronic hypoxia has been newly proposed as a common mechanism of tubulointerstitial fibrosis in the progression of various chronic inflammatory renal diseases, where PAI-1 plays an important role in the accumulation of extracellular matrix (ECM) through inhibition of plasmin-dependent ECM degradation. In the present study, we investigated the presence of PAI-1 in renal tubular cells by immunostaining renal biopsy samples. We also closely examined the effects of hypoxia and TNF-alpha on PAI-1 expression in cultured human proximal renal tubular cells (HRCs). Confluent cells growth-arrested in DMEM for 24h were exposed to hypoxia (1% O2) and/or TNF-alpha at 10 ng/ml for 24 hours. Amounts of PAI-1 protein and mRNA after stimulation were measured by ELISA and TaqMan quantitative PCR, respectively and compared to those in cells incubated under control conditions (18% O2 without TNF-alpha). HIF-1alpha was demonstrated by immunoblot analysis. In crescentic glomerulonephritis, clusters of proximal tubules were specifically stained for PAI-1. Treatment of 24 hours with hypoxia, TNF-alpha and their combination induced a 2.7-fold, a 1.8-fold, and a 4.6-fold increase in PAI-1 protein secretion, and produced a 3.6-fold, a 3.3-fold, and a 12.1-fold increase at the PAI-1 mRNA level, respectively. Immunoblot analysis revealed that hypoxia-inducible factor-1alpha (HIF-1alpha) was markedly accumulated in the nuclear fraction after 16-hours exposure of HPTECs to hypoxia but not to TNF-alpha. In conclusion, hypoxia induces PAI-1 expression via remarkable nuclear accumulation of HIF-1alpha in HRCs. TNF-alpha can enhance this hypoxia-induced PAI-1 expression.     

Glucagon-induced somatostatin release from perifused rat hypothalamus: calcium dependency and effect of cysteamine treatment

Somatostatin (SRIF) release from rat hypothalamus was investigated in vitro with a perifusion system. Glucagon (1 microM) and high potassium concentrations (56 mM) stimulated SRIF release in a calcium-dependent manner. Pretreatment of the rat with cysteamine (30 mg/100 g body weight, 7 h earlier) significantly reduced SRIF release from the hypothalamus in glucagon- and high potassium-stimulated states as well as in the basal state. SRIF release from rat hypothalamus was also stimulated by both dibutyryl cyclic AMP (1 mM) and theophylline (3 mM). These results suggest that glucagon, acting in a calcium-dependent manner and possibly through the adenylate cyclase-cyclic AMP system, stimulates SRIF release from rat hypothalamus and that cysteamine treatment reduces releasable SRIF in the hypothalamus.     

In vivo effects of phenytoin and phenobarbital on GABA receptors in rat cerebral cortex and cerebellum

The in vivo effects of anticonvulsants on specific binding of [3H]GABA in the rat brain were examined in male Wistar rats. Acute treatment with phenobarbital increased specific [3H]GABA binding in the cerebral cortex, whereas repeated treatment with phenobarbital failed to change [3H]GABA binding. [3H]GABA binding in the cerebellum was not influenced by phenobarbital administration. Acute treatment with phenytoin produced no change in [3H]GABA binding, whereas repeated treatment with phenytoin caused a significant increase in [3H]GABA binding in the cerebellum, but not in the cerebral cortex. The effects of these anticonvulsants may be due, at least in part, to GABA receptor-mediated mechanisms.     

Effects of food deprivation and high fat diet on opioid receptor binding in rat brain

The effect of food deprivation for 72 h or a high fat diet on [3H]naloxone binding in the discrete brain regions of male lean Zucker rats was studied. In the midbrain, both treatments increased Bmax for the high-affinity site with no change in Kd. In the cortex, the high fat diet increased Bmax for the high-affinity site. These results suggest that dietary manipulations could produce significant changes in the endogenous opioid system.     

Galanin stimulates the release of vasoactive intestinal polypeptide from perifused hypothalamic fragments in vitro and from periventricular structures into the cerebrospinal fluid in vivo in the rat

Intracerebroventricular injection of galanin (2 micrograms/rat) raised plasma prolactin (PRL) levels in the rat, which was accompanied by an increase in immunoreactive vasoactive intestinal polypeptide (VIP) in the cerebrospinal fluid (CSF). Immunoreactive VIP release from superfused rat hypothalamic fragments in vitro was dose-relatedly stimulated by galanin (10(-7) and 10(-8) M). PRL release from superfused rat anterior pituitary cells was stimulated by TRH (10(-8) M) but not affected by galanin (10(-7) to 10(-5) M). These findings indicate that central galanin has a stimulating role in the release of hypothalamic VIP, which results in pituitary PRL secretion in the rat.     

Nonlinear mixed effect modeling of the pharmacodynamics of natriuretic peptides in rats

Natriuretic peptides have not only natriuretic/diuretic but also hypotensive activities, and the decreased renal perfusion caused by the excessive hypotension is known to attenuate the diuretic actions. The present study was designed to examine the relationship between the dosing (intravenous constant infusion) rates and the diuretic actions of -rat atrial natriuretic peptide (-rANP) and rat brain natriuretic peptide (rBNP) in rats, and population (nonlinear mixed effect model) analysis was applied to these complicated diuretic actions. The intrinsic diuretic activities of -rANP and rBNP could be analyzed, and the effects of blood pressure, heart rate, and also inhibition of degradation enzyme on the diuresis of natriuretic peptides were estimated simultaneously. The population analysis was useful for analyzing such pharmacodynamic data for which the individual analysis could not be applied easily.     

Osteoplastic laminoplasty for cervical myeloradiculopathy secondary to ossification of the posterior longitudinal ligament

Summary Forty-seven patients with cervical myeloradiculopathy due to ossification of the posterior longitudinal ligament were treated by laminoplasty. The spinal canal from C3 to C7 was opened en bloc unilaterally and a spacer bone graft inserted to separate the floating laminae. The average follow up was 7.3 years (range 5 to 11 years). Favourable results were obtained in 35 patients and even though they had serious postoperative symptoms those with advanced neurological symptoms before operation showed considerable improvement. Late results were poor in patients who had greater than 50% compromise of the spinal canal by the ossified lesion. Laminoplasty is a safer method of obtaining favourable late results in patients with involvement of more than 3 vertebrae, but in those with a more severe compromise of the spinal canal by ossification, additional anterior decompression may be necessary later.

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Résumé Cet article présente les résultats à long terme de laminoplasties pratiquées pour myéloradiculopathie cervicale due à l'ossification du ligament vertébral commun postérieur, ainsi que les modifications observées dans les canaux rachidiens élargis. Habituellement le canal rachidien a été ouvert en bloc de C3 à C7, d'un seul côté, puis complété par une greffe osseuse afin de maintenir l'ouverture au niveau de la lame. On a utilisé la cotation de l'Association orthopédique japonaise, concernant la myélopathie cervicale, pour évaluer l'état des patients avant l'intervention chirurgicale, puis 2 ou 3 mois après la sortie et durant la période de surveillance. Les 47 patients de cette étude ont été suivis de 5 à 11 ans, soit en moyenne 7,3 ans. Les résultats finaux ont été favorables chez 35 patients et, même quand la symptomatologie postopératoire avait été assez préoccupante, les malades qui présentaient des symptômes neurologiques majeurs étaient notablement améliorés. Les résultats étaient mauvais chez les patients dont le rétrécissement du canal rachidien était supérieur à 50% (p<0.05). Il semble que la laminoplastie soit le moyen le plus sûr d'obtenir un résultat favorable mais une décompression antérieure complémentaire peut être nécessaire chez les patients atteints d'une sténose sévère due à une ossification du ligament vertébral postérieur.

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Presented in part at SICOT 93, Seoul, Korea, 28 August–3 September, 1993