A Subset of Patients With Recurrent Spontaneous Abortion Is Deficient in Transforming Growth Factor β-2-Producing “Suppressor Cells” in Uterine Tissue Near the Placental Attachment Site

PROBLEM : To determine if patients with unexplained recurrent miscarriage have a deficiency of decidual immunosuppressor cells that produce transforming growth factor β type 2, as has been found in mice with abortion due to rejection and/or trophoblast failure. METHODS : Decidual biopsy specimens were taken as near to the placental attachment site as possible under ultrasound guidance from first trimester legal termination (control) patients with recurrent miscarriage and non-viable pregnancy, and from patients with sporadic missed abortion. The tissue was tested for TGFβ-2⁺ suppressor cells by in situ hybridization, immunohistochemistry, and analysis of supernatants. RESULTS : TGFβ-2-related suppressor molecules similar but not identical to those identified in pregnant mice were released by decidual lymphoid cells. Fifty percent of 14 recurrent miscarriage patients showed a lack of suppressor cells and 59% were subnormal in comparison to 20 controls and 5 sporadic miscarriage patients, where 80–85% of the patients had detectable suppressor cells. CONCLUSIONS : Suppressor cell deficiency is compatible with a role for rejection and/or trophoblast failure in some patients with recurrent miscarriage. Presence of suppressor cells in most patients with missed abortion (4/5) is compatible with an alternative cause of fetal death, similar to findings reported in genetic fetal death mice.     

神经生长因子治疗颅脑损伤52例

本文报告用水囊引产胎儿脑黑质制备的神经生长因子(NGF)治疗52例颅脑损伤的临床观察结果:显效率91%。有效率100%,轻、中型患者疗效明显,显效率100%。其中头昏头痛,语言障碍,精神异常,大小便失禁,肢体功能障碍都有明显疗效。而且对儿童和病程短者效果更佳。认为治疗机理可能是 NGF 能预防神经元坏死,促进神经元及其纤维增生有关。结果表明,NGF 在治疗脑外伤及其后遗症中疗效确切,在颅外伤及其后遗症中可广为应用。     

Relations between vasoactive hormones and diastolic function in hypertensive uraemic patients

Background. Arterial hypertension is a significant risk factor for the high rate of cardiovascular disease in chronic uraemic (CU) patients. Any role that hypertension may play in CU patient outcomes assumes added significance. The elevation of some hormonal factors in early clinical stage could represent a valuable marker of cardiac disease in CU. Aim. This study first investigated the role of several hormones on cardiac diastolic properties in CU patients. Moreover, the study investigated the association of hypertension with both diastolic function and release of vasoactive hormones in CU patients. Results. We have reported that the early impairment of diastolic function is correlated with the elevation of both circulating plasma atrial natriuretic factor and endothelin-1 (ET-1) in hypertensive CU patients. Since the effect of ET-1 on diastolic function is still poorly understood, we have investigated also this issue. In eight additional patients with reduced E/A ratio, but without uraemia, hypertension or chronic heart failure, we have showed a high inverse correlation between the values of E/A ratio and ET-1 plasma concentrations. Conclusions. These results strongly suggest that the elevation in ET-1 levels was correlated with diastolic dysfunction in man. This phenomenon may have important pathophysiological implications suggesting the possibility of an early therapeutic approach in these patients.     

Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.     

PAF antagonistic activity of 2-hydroxy-3-methoxybenzoic acid glucose ester fromGentiana scabra

In order to find out anti-platelet activating factor (PAF) from natural resources, Korean medicinal plants used for the treatments of peripheral circulation disorders were tested for their possible protective effects on PAF-induced anaphylactic shock. From the above screening, the methanol extract ofGentiana scabra showed a potent antagonistic activity against PAF. Water suspension of the extract was partitioned with CH₂Cl₂ and EtOAc, successively. The EtOAc fraction which showed the highest activity was chromatographed on silica gel to yield 6 fractions. From the fraction which showed higher PAF-antagonistic activity than the other fractions, compound1 was isolated by recrystallization. On the basis of spectral data, compound1 was identified as 2-hydroxy-3-methoxybenzoic acid glucose ester. The compound prevented the mice from the PAF-induced death at a dose of 300 μg/mouse.     

NGF prevents the changes induced by monocular deprivation during the critical period in rats

Photic evoked responses were recorded from the striate cortex of Long-Evans hooded intact, monocular visual deprivation (MD) and MD treated with NGF rats. The averaged visual evoked responses (AVER) were obtained from both hemispheres and provided comparison after binocular photic stimuli between the contralateral and the ipsilateral striate cortex with relation to the MD eye. One month of monocular visual deprivation at the critical period of development resulted in marked reduction of the amplitudes of AVER components as compared to the control recordings (P < 0.001). These changes of the AVER could be prevented by NGF infusion to lateral ventricle at the dosage of 2.0–2.4 μg/day for four weeks during the monocular deprivation. In conclusion, the change of AVER amplitudes induced by monocular visual deprivation during the critical period of development can be prevented by NGF infusion to lateral ventricle.     

NGF Augmentation rescues trigeminal ganglion and principalis neurons,but not brainstem or cortical whisker patterns,after infraorbital nerve injury at birth

Prior studies indicate that neonatal nerve injury kills many trigeminal (V) first- and second-order cells, and interrupts pattern formation in the brainstem and cerebral cortex. Yet it is not known whether effects upon cell survival and pattern formation are causally related. To determine whether axotomized V ganglion cells can be rescued by an exogenous trophic agent, rats received 5 mg/kg of nerve growth factor (NGF) prior to, and every day after, infraorbital nerve section on the day of birth until sacrifice on postnatal day (PND) 1, 3, 5, 7, or 14. Other animals received identical lesions without NGF. Ganglion cell numbers were significantly reduced by PNDl in pups not given NGF, while NGF-treated rats displayed no significant cell loss through PND7. However, NGF did not permanently rescue V neurons because ganglion cell numbers were reliably reduced by PND14. Cell numbers in V nucleus principalis were reduced by PNDl in pups not given NGF, while NGF-treated animals displayed no cell loss through PND14. NGF's rescue of second-order cells is probably an indirect effect of NGF actions upon V ganglion cells because, in other newborns, NGF failed to maintain principalis cells after direct lesion of the left V ganglion. To determine whether preventing cell death permits whisker-related pattern formation, other rats also received NGF prior to and after infraorbital nerve section at birth. After 3–14 days, patterns were assessed in the brainstem and cortex with cytochrome oxidase histochemistry and serotonin immunocytochemistry. Whisker-related patterns failed to develop as in cases not given NGF. These data indicate that communication with the periphery is necessary for the maintenance of central whisker-related patterns. They also suggest that V ganglion cells can be rescued, albeit temporarily, from rapid injury-induced death by NGF, thereby delaying injury-induced cell death in nucleus principalis. However, the mechanism(s) responsible for injury-induced pattern alterations in the developing V system remains to be elucidated. © 1993 Wiley-Liss, Inc.