Proliferative lesions of oviduct and uterus in CD-1 mice exposed prenatally to tamoxifen

Tamoxifen (TAM) is widely used as adjuvant breast cancer therapy after surgery and as a chemopreventive agent in women of child-bearing age. However, TAM therapy has been shown to result in an increased incidence of endometrial carcinoma in women. The present study was designed to investigate the effects of TAM (5 mg/kg and 7.5 mg/kg body wt) given i.g. to pregnant CD-1 mice (1x/day, days 12 through 18 of gestation) on their female offspring. Progressive proliferative hyperplasia of the oviduct was frequently seen in TAM-exposed offspring, reaching 100% incidence by 52 weeks in both treatment groups. These females also developed progressive proliferative uterine lesions, including moderate/severe cystic endometrial hyperplasia (34-50%) and polypoid adenomas (27-30%) between 53 and 78 weeks. Deciduomas (15%) occurred at young ages (12 and 24 weeks) while leiomyomas (14%), a malignant leiomyosarcoma, and ovarian granulosa cell tumors (14%), were found between 72 and 78 weeks. Our findings thus suggest a strong association between transplacental TAM and reproductive tract abnormalities in female CD-1 mice.      

The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children

OBJECTIVE: The ketogenic diet is a high-fat, low-protein, low-carbohydrate diet developed in the 1920s for the treatment of children with difficult to control seizures. Despite advances in both the pharmacotherapy and the surgery of epilepsy, many children continue to have difficult-to-control seizures. This prospective study sought to determine the ketogenic diet's effectiveness and tolerability in children refractory to today's medications. METHODS: One hundred fifty consecutive children, ages 1 to 16 years, virtually all of whom continued to have more than two seizures per week despite adequate therapy with at least two anticonvulsant medications, were prospectively enrolled in this study, treated with the ketogenic diet, and followed for a minimum of 1 year. Seizure frequency was tabulated from patients' daily seizure calendars and seizure reduction calculated as percentage of baseline frequency. Adverse events and reasons for diet discontinuation were recorded. RESULTS: The children (mean age, 5.3 years), averaged 410 seizures per month before the diet, despite an exposure to a mean of 6.2 antiepileptic medications. Three months after diet initiation, 83% of those starting remained on the diet and 34% had >90% decrease in seizures. At 6 months, 71% still remained on the diet and 32% had a >90% decrease in seizures. At 1 year, 55% remained on the diet and 27% had a >90% decrease in seizure frequency. Most of those discontinuing the diet did so because it was either insufficiently effective or too restrictive. Seven percent stopped because of intercurrent illness. CONCLUSIONS: The ketogenic diet should be considered as alternative therapy for children with difficult-to-control seizures. It is more effective than many of the new anticonvulsant medications and is well tolerated by children and families when it is effective.     

Mononucleosis syndrome and coincidental human herpesvirus-7 and Epstein-Barr virus infection

Two girls (a 5 year old and a 21 month old) experiencing mononucleosis syndrome with coincidental human herpesvirus (HHV)-7 and Epstein-Barr virus (EBV) infections are described. One patient had primary HHV-7 infection and reactivated EBV infection. The other had primary HHV-7 and EBV infections. These cases indicated that HHV-7 is capable of inducing infectious mononucleosis-like illness. Multiple herpesvirus infection in one of the patients also suggests that interaction among herpesviruses can occur in vivo. The consequence of this interaction may have clinical implications.     

维A类化合物4-APR抑制肿瘤侵袭、转移的作用

用体内外实验模型,研究了新维A类化合物4-乙酰胺苯基维A酸酯(4-APR)对肿瘤侵袭、转移的抑制作用。4-APR 43.3mg·kg^-1po即能减少小鼠Lewis肺癌的自发性肺转移瘤数。半体内实验证明4-APR10^-5mol·L^-1和10^-6mol·L^-1对B16-F10癌细胞的人工肺转移瘤数分别抑制67.9%和36.6%。体外实验显示,4-APR对B16-F10细胞侵袭重组基底膜的抑制率分别为54.2%和41.9%。     

Assembly of contact-phase factors on the surface of the human neutrophil membrane

H-kininogen (HK), a major factor involved in contact-phase activation, was recently immunolocalized on the external surface of human neutrophils. Experiments were, therefore, designed to consider the question of whether the complete assembly of contact factors occurs on the outer surface of the neutrophil membrane. By immunolocalization techniques, and using specific antibodies directed against the various contact factors, we now demonstrate that plasma prekallikrein (PK), factor XI (FXI), and factor XII (FXII) are present on the exterior face of the human neutrophil. Failure to localize HK, PK, or FXI by monoclonal antibodies directed to their reciprocal binding sites, and displacement of PK/FXI by peptide HK31, which mimics the relevant binding site(s) of HK, suggested that prekallikrein and FXI are anchored to the neutrophil membrane through attachment to the kininogen molecule. Probing of the kinin moiety by a specific antibody showed that kininogen molecules bound to the neutrophil cell membrane contain the kinin sequence, which can be released by plasma kallikrein or by tissue kallikrein. Our results led us to the novel conclusion that neutrophils provide a circulating platform for the components of the contact-phase system.     

Hemorrhagic tumor necrosis during a pilot trial of tumor necrosis factor-alpha and anti-GD3 ganglioside monoclonal antibody in patients with metastatic melanoma

Hemorrhagic tumor necrosis is an inflammatory event that leads to selective destruction of malignant tissues, with both potentially toxic and beneficial consequences. A pilot clinical trial was undertaken combining tumor necrosis factor-alpha (TNF-alpha) with the monoclonal antibody R24 (MoAb R24) against GD3 ganglioside in patients with metastatic melanoma. Patients received MoAb R24 to recruit leukocytes to the tumor followed by low doses of recombinant TNF-alpha to activate leukocytes. Eight patients were treated and seven patients had mild toxicity. One patient with extensive metastatic melanoma developed tumor lysis syndrome within hours after treatment with almost complete necrosis of bulky tumors in multiple visceral sites. To our knowledge, this is the first documented case of hemorrhagic tumor necrosis in a patient with metastatic cancer in multiple visceral sites.     

In vivo expression of the B7 costimulatory molecule by subsets of antigen-presenting cells and the malignant cells of Hodgkin's disease

The B-lymphocyte/accessory-cell activation antigen B7 (BB1) has been shown in vitro to stimulate T-lymphocyte proliferation and cytokine production via CD28 present on the latter cells. In this study, benign lymphoid tissues, lymphomas, and extralymphoid inflammatory sites were examined immunohistochemically using anti-B7 and other relevant monoclonal antibodies. B7 was expressed by benign transformed germinal center B cells, as it was by B cells of follicular lymphomas. B7 was also expressed by a subpopulation (a mean of 31% to 65%) of macrophages and dendritic cells in a variety of lymphoid tissues. It was present in abundance on all macrophages constituting sarcoid granulomas in lymph nodes. In extralymphoid inflammation, 17% to 35% of macrophages expressed B7 only weakly. Cases of Hodgkin's disease showed expression of B7 by the majority of Reed-Sternberg cells or malignant mononuclear variants, a phenomenon that potentially contributes to the lymphocytic accumulation that is a feature of this condition. CD28+ T cells were seen in all areas where T cells were present. B7+ and CD28+ cells colocalized in, for example, lymphoid follicles, lymph node paracortex, sarcoid granulomas, and Hodgkin's disease tissue, indicating a potential for cellular interaction via these molecules at these sites.