^131I—C50放射免疫显像诊断卵巢癌

目的 探讨卵巢癌放免显像在卵巢癌诊断和治疗方面的临床价值。方法 采用氯胺T法制备^131I-CEA McAb(C50)，以静脉滴注方式给药，于不同时间对患者进行显像。结果 经手术和病理检查证实的105例卵巢癌患者中96例显像阳性，9例阴性（假阴性）；23例良性病灶中22例获阴性显像结果，并经手术证实。96例阳性显像中87例放射免疫显像分期与手术分期完全相符。151处转移灶发现141处，阳性率93．4％，最小检出病灶直径1cm。结论 卵巢癌放免显像对卵巢癌的早期发现，指导临床分期和制定治疗方案、预计预后有较高的临床价值。     

A comparison of acid-elution techniques and alpha-fetoprotein levels for the detection of fetomaternal bleeding

Practical and reliable methods to identify and/or quantitate fetal blood are becoming more important in the modern practice of obstetrics. In this study, two commercially available acid-elution techniques were compared with plasma -alpha-fetoprotein (AFP) by simultaneously testing samples of fetal blood mixed with adult blood in fixed ratios. Thirty-one samples representing a range of amounts of fetomaternal hemorrhage, from 0.024 to 48 ml, were analyzed. The acid-elution techniques were equally effective in detecting fetomaternal hemorrhage greater than 15 ml, but the bmc Reagent set was the most accurate for detection of small numbers of fetal erythrocytes. The accuracy of AFP was greater than that of either acid-elution technique, but its clinical usefulness is limited by the necessity for a prehemorrhage sample.     

Hazards of calcium gluconate therapy in the newborn infant: intra-arterial injection producing intestinal necrosis in rabbit ileum

Five infants received 10% calcium gluconate via umbilical artery catheters, which resulted in intestinal bleeding and lesions of the buttock, anus, groin, and thigh. The effects of intra-arterial calcium gluconate in two animal models were investigated. Injection of calcium into the aorta in the region of the posterior mesenteric artery resulted in immediate hyperperfusion of the descending colon; this may be an early hemodynamic response to injury in the area of colon supplied by this vessel. Injections into the arterial arcade of the rabbit ileum resulted in intestinal necrosis and villous atrophy. The use of umbilical artery catheters for administration of calcium gluconate is potentially hazardous.     

Reversible dementia temporally associated with intraventricular therapy with methotrexate in a child with acute myelogenous leukemia.

During maintenance therapy with intraventricular methotrexate, progressive dementia developed in a child with meningeal leukemia. Cerebrospinal fluid levels of MTX were in the nontoxic range and neurologic evaluation failed to demonstrate anatomic obstruction, infection, or folate depletion. The patient's symptoms gradually resolved when the methotrexate was discontinued, suggesting that methotrexate neurotoxicity may occur in the absence of an elevated CSF concentration of MTX.     

Excitatory synaptic transmission and its modulation by PKC is unchanged in the hippocampus of GAP-43-deficient mice

We compared excitatory synaptic transmission between hippocampal pyramidal cells in dissociated hippocampal cell cultures and in area CA3 of hippocampal slice cultures derived from wild-type mice and mice with a genetic deletion of the presynaptic growth associated protein GAP-43. The basal frequency and amplitude of action potential-dependent and -independent spontaneous excitatory postsynaptic currents were similar in both groups. The probability that any two CA3 pyramidal cells in wild-type or GAP-43 knockout (-/-) slice cultures were synaptically connected was assessed with paired recordings and was not different. Furthermore, unitary synaptic responses were similar in the two genotypes. Bath application of phorbol 12,13-diacetate (0.6-3 microM) elicited a comparable increase in the frequency of miniature excitatory synaptic currents in wild-type and GAP-43 (-/-) cultures. This effect was blocked by the protein kinase C inhibitor, bisindolylmaleimide I (1.2 microM). Finally, 3 microM phorbol 12,13-diacetate potentiated the amplitude of unitary synaptic currents to a comparable extent in wild-type and GAP-43 (-/-) slice cultures. We conclude that GAP-43 is not required for normal excitatory synaptic transmission or the potentiation of presynaptic glutamate release mediated by activation of protein kinase C in the hippocampus.     

Inhibition of angiogenesis in vivo and growth of Kaposi's sarcoma xenograft tumors by the anti-malarial artesunate

Artesunate (ART) is a semi-synthetic derivative of the sesquiterpene artemisinin used for the second line therapy of malaria infections with Plasmodium falciparum. ART also inhibits growth of many transformed cell lines. In the present investigation, we show that ART inhibited the growth of normal human umbilical endothelial cells and of KS-IMM cells that we have established from a Kaposi's sarcoma lesion obtained from a renal transplant patient. The growth inhibitory activity correlated with the induction of apoptosis in KS-IMM cells. Apoptosis was not observed in normal endothelial cells, which, however, showed drastically increased cell doubling times upon ART treatment. ART strongly reduced angiogenesis in vivo in terms of vascularization of Matrigel plugs injected subcutaneously into syngenic mice. We conclude that ART represents a promising candidate drug for the treatment of the highly angiogenic Kaposi's sarcoma. As a low-cost drug, it might be of particular interest for areas of Kaposi's sarcoma endemics. ART could be useful for the prevention of tumor angiogenesis.     

Structural requirements for the flavonoid-mediated modulation of glutathione S-transferase P1-1 and GS-X pump activity in MCF7 breast cancer cells

The objective of this study was to investigate the structural requirements necessary for inhibition of glutathione S-transferase P1-1 (GSTP1-1) and GS-X pump (MRP1 and MRP2) activity by structurally related flavonoids, in GSTP1-1 transfected MCF7 cells (pMTG5). The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some flavonoids. Especially galangin was able to inhibit almost all cellular GSTP1-1 activity upon exposure of the cells to a concentration of 25microM. Other flavonoids like kaempferol, eriodictyol and quercetin showed a moderate GSTP1-1 inhibitory potential. For GSTP1-1 inhibition, no specific structural requirements necessary for potent inhibition could be defined. Most flavonoids appeared to be potent GS-X transport inhibitors with IC(50) values ranging between 0.8 and 8microM. Luteolin and quercetin were the strongest inhibitors with IC(50) values of 0.8 and 1.3microM, respectively. Flavonoids without a C2-C3 double bond like eriodictyol, taxifolin and catechin did not inhibit GS-X pump activity. The results of this study demonstrate that the structural features necessary for high potency GS-X pump inhibition by flavonoids are (1) the presence of hydroxyl groups, especially two of them generating the 3',4'-catechol moiety; and (2) a planar molecule due to the presence of a C2-C3 double bond. Other factors, like lipophilicity and the total number of hydroxyl groups do not seem to be dominating the flavonoid-mediated GS-X pump inhibition. To identify the GS-X pump responsible for the DNP-SG efflux in MCF7 cells, the effects of three characteristic flavonoids quercetin, flavone and taxifolin on MRP1 and MRP2 activity were studied using transfected MDCKII cells. All three flavonoids as well as the typical MRP inhibitor (MK571) affected MRP1-mediated transport activity in a similar way as observed in the MCF7 cells. In addition, the most potent GS-X pump inhibitor in the MCF7 cells, quercetin, did not affect MRP2-mediated transport activity. These observations clearly indicate that the GS-X pump activity in the MCF7 cells is likely to be the result of flavonoid-mediated inhibition of MRP1 and not MRP2. Altogether, the present study reveals that a major site for flavonoid interaction with GSH-dependent toxicokinetics is the GS-X pump MRP1 rather than the conjugating GSTP1-1 activity itself. Of the flavonoids shown to be most active especially quercetin is frequently marketed in functional food supplements. Given the physiological levels expected to be reached upon supplement intake, the IC(50) values of the present study point at possible flavonoid-drug and/or flavonoid-xenobiotic interactions especially regarding transport processes involved in toxicokinetics.     

Visual emotional stimuli modulation of auditory sensory gating studied by magnetic P50 suppression

The auditory sensory gating system modulates its sensitivity to incoming stimuli and prevents higher brain functions from sensory overload in the primary auditory cortex. We investigated whether visually evoked emotional stimuli affect auditory sensory gating. Magnetic P50 (P50m) suppression was evaluated by magnetoencephalography in fifteen healthy subjects while they viewed slides varying in emotional valence and arousal. The ratio of strength of dipole moments of the 2^nd to the 1^st P50m and the anatomical location of their sources were calculated. Negatively valenced slides significantly attenuated P50m suppression, as compared to neutral ones, while the effects of positive slides were insignificant. No effects on latencies or the location of P50m sources were observed. Thus, negative emotional stimuli may modulate sensory gating.