Antitumor activity of a recombinant soluble betaglycan in human breast cancer xenograft

We have demonstrated previously that ectopic expression of a soluble betaglycan, also known as transforming growth factor (TGF) beta type III receptor, can suppress the malignant properties of human carcinoma cells by antagonizing the tumor-promoting activity of TGF-beta (A. Bandyopadhyay et al., Cancer Res., 59: 5041-5046, 1999). In the current study, we investigated the potential therapeutic utility of a recombinant preparation of human and rat soluble betaglycan (sBG). Purified recombinant human sBG showed similar properties to its rat counterpart (M. M. Vilchis-Landeros et al., Biochem J., 355: 215-222, 2001). It bound TGF-beta with high affinity and isoform selectivity and neutralized the activity of TGF-beta(1) in two bioassays. Peritumoral (50 micro g/tumor, twice a week) or i.p. (100 micro g/animal, every alternate day) injection of sBG into human breast carcinoma MDA-MB-231 xenograft-bearing athymic nude mice significantly inhibited the tumor growth. The administration of sBG also reduced metastatic incidence and colonies in the lungs. The tumor-inhibitory activity of sBG was found to be associated with the inhibition of angiogenesis. Systemic sBG treatment significantly reduced tumor microvessel density detected with histological analyses and CD-31 immunostainings, as well as tumor blood volume measured with hemoglobin content. In an in vitro angiogenesis assay, treatment with the recombinant sBG significantly reduced the ability of human dermal microvascular endothelial cells to form a capillary tube-like structure on Matrigel. These findings support the conclusion that sBG treatment suppresses tumor growth and metastasis, at least in part by inhibiting angiogenesis. As such, it could be a useful therapeutic agent to antagonize the tumor-promoting activity of TGF-beta.     

Okadaic acid induces epileptic seizures and hyperphosphorylation of the NR2B subunit of the NMDA receptor in rat hippocampus in vivo

Overactivation of N-methyl-D-aspartate (NMDA) glutamate receptors is closely related to epilepsy and excitotoxicity, and the phosphorylation of these receptors may facilitate glutamate-mediated synaptic transmission. Here we show that in awake rats the microinjection into the hippocampus of okadaic acid, a potent inhibitor of protein phosphatases 1 and 2A, induces in about 20 min intense electroencephalographic and behavioral limbic-type seizures, which are suppressed by the systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine hydrogen maleate and by the intrahippocampal administration of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinases. Two hours after okadaic acid, when the EEG seizures were intense, an increased serine phosphorylation of some hippocampal proteins, including an enhancement of the serine phosphorylation of the NMDA receptor subunit NR2B, was detected by immunoblotting. Twenty-four hours after okadaic acid a marked destruction of hippocampal CA1 region was observed, which was not prevented by the receptor antagonists. These findings suggest that hyperphosphorylation of glutamate receptors in vivo may result in an increased sensitivity to the endogenous transmitter and therefore induce neuronal hyperexcitability and epilepsy.     

Lyme disease--part I: epidemiology and etiology

Lyme disease (LD) is a tick-borne disease that typically presents with myalgia, fatigue, and a characteristic rash. LD occurs worldwide, and its incidence continues to increase. Prevention and early diagnosis based on increased understanding of disease transmission and pathomechanisms are crucial in stopping LD from progressing to its later stages. In this article, the first of a 2-part series on LD, we review epidemiologic and etiologic factors.     

Neocortical hyperexcitability after GABA withdrawal in vitro

The sharp interruption of the intracortical instillation of exogenous gamma-aminobutyric acid (GABA), generates an epileptic focus in mammals. Seizures elicited by GABA withdrawal last several days or weeks. The present work reports that GABA withdrawal-induced hyperexcitability can be produced in vitro: a sudden withdrawal of GABA (5 mM; 120 min) or benzodiazepine (60 microM flunitrazepam) from the superfusion, induced a gradual increase in the amplitude of the evoked population spike (PS) recorded on neocortical slices. PS enhancement reached 150% above the control value 2.5 h after GABA withdrawal. GABA withdrawal-induced hyperexcitability was facilitated by progesterone. PS enhancement induced by GABA withdrawal was associated with an impairment of GABA transmission occurring before epileptiform discharges were fully established. Paired pulse inhibition and evoked [3H]-GABA release appear decreased; suggesting that cortical hyperexcitability as a result of GABA withdrawal involves pre-synaptic changes. Specific muscimol binding decreased during GABA superfusion but recovered after GABA withdrawal. However, the sensitivity of the post-synaptic response to 3alpha-OH-5alpha-pregnan-20-one or allopregnanolone (alloP) was enhanced after GABA withdrawal, suggesting a functional change in the GABA(A) receptors. The changes described may be the cellular correlates of the withdrawal syndromes appearing after interruption of the administration of GABA(A) receptor agonists.     

Bilateral successive testicular cancer of different cell type

The incidence of bilateral successive testicular cancer of different histologic cell type is rare. This is a case of second primary tumor found twelve years after the first primary cancer by self-examination of the contralateral testis by the patient.     

A community-based study of hepatitis B infection and immunization among young adults in a high-drug-use neighborhood in New York City

We conducted a community-based study of the prevalence and correlates of hepatitis B virus (HBV) infection and immunization among young adults in a “drug supermarket” neighborhood in New York City. Four hundred eighty-nine young adults ages 18–24 years were recruited from Bushwick, Brooklyn through multistage household probability sampling (n=332) and targeted sampling (n=157), interviewed, and tested for three hepatitis B markers (HBsAg, anti-HBc, and anti-HBs). Serological evidence of HBV infection was found in 8.0% (6.0% in the household sample and 12.1% in the targeted sample) and of hepatitis B immunization in 19.6% (22.6% in the household sample and 13.4% in the targeted sample). HBV infection was higher among young adults who either used crack or injected drugs and among those who traded sex for money or drugs. Having Medicaid was significantly associated with lower odds of infection in the household sample and higher odds of immunization in the targeted sample. Although adolescent hepatitis B immunization has been a public health priority in the United States since 1995, nearly three-quarters of young adults in this community did not have serological evidence of being either exposed or immunized. Whereas subsequent younger generations benefited from universal childhood hepatitis B immunization, this particular cohort of young adults who live in communities like Bushwick presents a unique group for prevention intervention. The opinions expressed herein are those of the authors and not of USAID or other organizations to which the authors belong.