Insulin-like growth factor binding protein-3 induces early apoptosis in malignant prostate cancer cells and inhibits tumor formation in vivo

BACKGROUND: Insulin-like growth factor binding protein (IGFBP-3) levels are significantly reduced in malignant prostate epithelial cells. In this study, we evaluated the role of endogenous IGFBP-3 on prostate cancer cell growth and tumorigenesis. METHODS: IGFBP-3 was re-expressed by stable transfection of human IGFBP-3 cDNA in a model of human prostate cancer, M12, a malignant subline in which IGFBP-3 levels are undetectable in comparison to the parent epithelial cell, P69. Effect of IGFBP-3 re-expression (M12-BP-3) on growth kinetics, morphology, propensity to apoptosis, and in vivo tumor formation were studied. RESULTS: M12-BP-3 cells secreted IGFBP-3 and growth arrested at a cell density that was threefold lower than control cells and this was associated with marked alteration in cell morphology. Control cells when grown in conditioned media secreted by M12-BP-3 also showed altered morphology compared to when cultured in IGFBP-3-immunodepleted conditioned media. The M12-BP-3 clones showed altered mitochondrial membrane potential, increased PARP cleavage, increase in sub-G1 peak, decreased levels of neuron specific enolase, and decreased tumor formation in athymic, nude mice. CONCLUSIONS: These data suggest that IGFBP-3 induces early apoptosis and has potential tumor suppressive effect in prostate cancer. Prostate 51: 141-152, 2002.     

Influence of GSTT1 and GSTM1 genotypes on sunburn sensitivity

Background: Exposure to sunlight may cause sunburn, skin cancer or phototoxic reactions to certain drugs such as Hypericum extract. All these are ultraviolet B (UVB)-mediated reactions which may be modulated by individual genetic susceptibility. UVB exposure results in oxidative stress. Many products of oxidative stress are detoxified by glutathione-S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). Deletion polymorphisms (genotype *0/*0) of GSTM1 and GSTT1 occur in 50% and 20% of Caucasians, respectively. By affecting the individual ability to detoxify oxidative stress-related products, they may influence the severity of the cutaneous photoreaction. Methods: Minimal erythema doses (MED) of UVB irradiation on the skin were determined in 110 subjects who were selected according to their GSTT1 genotype (28 GSTT1*0/*0, 54 GSTT1*A/*0, and 28 GSTT1*A/*A). Genotypes were detected with novel polymerase chain reaction (PCR) assays that allow the differentiation between homozygous and heterozygous GSTT1 and GSTM1 deletions. Results: In the absence of GSTT1 enzyme, the susceptibility of individuals to UVB-induced inflammatory skin reactions increased significantly (p = 0.02, ANCOVA). ‘Gene-equivalents’ were calculated from the number of functional GSTM1 and GSTT1 alleles as a measure of the gene-dose. UVB sensitivity correlated with gene dose up to a threshold above which additional GSTT1 or GSTM1 alleles did not provide additional protection. Volunteers who were homozygously deficient in GSTT1 and GSTM1 were most sensitive to UVB. Interestingly, individuals with high GSTM1 gene-doses showed increased photosensitization after administration of Hypericum extract (St. John’s wort). Conclusion: Individuals harboring the *0/*0 genotype of GSTT1 and/or GSTM1 showed enhanced UVB-induced cutaneous damage. Moreover, GST genotypes modulated Hypericum-induced photosensitization.     

Signs of miliary tuberculosis: which diagnostic tests and when to treat?

Three patients, men aged 21, 57 and 53 years, presented with variable non-specific symptoms such as general malaise, weight loss, elevated temperature, abdominal pain, cough, pulmonary crepitations and elevated liver enzymes. Diffuse fine nodular infiltration was seen on chest radiography in the last two cases. The first patient refused to be tentatively treated with tuberculostatics and died. Mycobacterium tuberculosis complex grew on L?wenstein medium a week later. The two other patients received tuberculostatic treatment. The second patient recovered, while the third patient suffered a cerebrovascular accident on top of emaciation and respiratory insufficiency and died. In the Netherlands, currently more than one hundred patients with tuberculosis disease die each year. The disease is mostly seen in people from the high-risk groups for tuberculosis such as asylum seekers and immigrants. Even after extensive diagnostic procedures it can be difficult to obtain rapid bacteriological confirmation. When miliary tuberculosis is suspected it is important to carry out the complete range of tests (Ziehl Neelsen microscopy, PCR, L?wenstein cultivation) and to start therapy immediately and not to await the results of the diagnostic tests. However, in many cases this may still be too late, with an estimated mortality of 20%.     

Regional myocardial dysfunction: evaluation of patients with prior myocardial infarction with fast CT

A prototype ultrafast cine computed tomographic (CT) scanner, designed specifically for cardiac imaging, was used to evaluate a preliminary series of patients with prior myocardial infarction (n = 21) and a control group without coronary artery disease (n = 5). Multilevel 50-msec CT scan exposures were obtained during peripheral intravenous bolus injections of contrast medium. A comparison was made between cine-CT scans and standard left ventriculographic images in assessing segmental left ventricular motion. Results indicate that cine CT, performed at sufficiently rapid speeds (20 scans per second) to allow useful analysis of regional ventricular wall motion, can provide adequate image quality. Analysis of 110 segments revealed a good correlation (90.9%) between the two techniques in characterizing normal from abnormal regional wall motion. Cine CT, based on this initial study, demonstrates considerable potential for evaluating not only cardiac chamber dimensions but also segmental wall dynamics.     

Cryofibrinogenemia in Henoch-Sch?nlein purpura: report of a case.

A patient with Henoch-Sch?nlein purpura (HSP) had exacerbations of disease that correlated closely with the presence of cryofibrinogenemia. Cryofibrinogen was absent consistently during asymptomatic intervals. To our knowledge, such a pattern has not been described previously in typical HSP. We suggest that all patients with HSP be screened for cryofibrinogenemia during the active phase of disease to determine the incidence of this abnormality.     

Three patients with orf (ecthyma contagiosum)

Orf was diagnosed in three patients: a 16-year-old Moroccan girl who had cut her finger in a butcher's shop, a 47-year-old Dutch woman who had allowed a lamb to suck on her finger on a children's farm, and a 50-year-old Dutch farm woman. Orf or ecthyma contagiosum is a well-known viral disease among sheep and goats. Transmission to humans as a zoonosis is rare but can take place via direct contact with infected animals or animal products. The clinical picture is usually characterized by a solitary lesion that develops on the dorsal side of the fingers or hands. This viral condition produces little or no systemic complaints and the lesions usually regress spontaneously without scar formation within 6 weeks (range 4-9 weeks). The correct diagnosis can usually be made on clinical grounds. The diagnosis may be confirmed by demonstration of the virus by electron microscopy or the polymerase chain reaction in fluid obtained from the skin lesions or by conventional histopathology. Early clinical recognition and knowledge of this benign, self-limiting viral condition is vital to avoid unnecessary surgical intervention. Proper information and reassurance of the infected patient are very important. All three patients recovered.