High Expression of Bloom Syndrome Helicase is a Key Factor for Poor Prognosis and Advanced Malignancy in Patients with Pancreatic Cancer: A Retrospective Study

Annals of Surgical Oncology - Bloom syndrome helicase (BLM) is overexpressed in multiple types of cancers and its overexpression may induce genomic instability. This study aimed to determine the...     

Telomerase inhibition with an oligonucleotide telomerase template antagonist: in vitro and in vivo studies in multiple myeloma and lymphoma

The effects of telomerase inhibition with an oligonucleotide N3' --> P5' thiophosphoramidate (GRN163) complementary to the telomerase template region were examined on human multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) cell lines, primary MM cells, and tumor xenografts. GRN163 treatment reduced telomerase levels in all cells and induced more rapid telomeric shortening. Continuous GRN163 treatment for 7 to 14 days resulted in proliferative arrest, morphologic changes, and apoptosis characteristic of cell crisis in tumor cell lines with short (1.7-5.4 kb) but not long (9-11 kb) telomeres. Intratumoral administration of GRN163 also inhibited the growth of MM and NHL xenografts established from cell lines with short telomeres (Hs602 lymphoma, 2.7 kb; CAG myeloma, 2.7 kb) and increased tumor apoptosis. However, GRN163 therapy of NHL xenografts established from cells with long telomeres (11.0 kb) had equivocal effects on tumor growth and did not induce apoptosis during this time frame. Systemic daily intraperitoneal administration of GRN163 in myeloma xenografts with short telomere lengths also decreased tumor telomerase levels and reduced tumor volumes. These data demonstrate that telomerase is important for the replication of mature B-cell neoplasia by stabilizing short telomeres, and they suggest that telomerase inhibition represents a novel therapeutic approach to MM and NHL.     

Comparison of the density of gamma-aminobutyric acid in the ventromedial prefrontal cortex of patients with first-episode psychosis and healthy controls

Background

Abnormality in the concentration and functioning of gamma-aminobutyric acid (γ-aminobutyric acid, GABA) in the brain is not only an important hypothetical link to the cause of schizophrenia but it may also be correlated with the cognitive decline and negative symptoms of schizophrenia. Studies utilizing high field magnetic resonance spectroscopy (MRS) report abnormal density of GABA in the ventromedial prefrontal cortex (vmPFC) of patients with chronic schizophrenia, but these results may be confounded by study participants’ prior use of antipsychotic medications.

Aim

Compare the density of GABA in the vmPFC of patients with first-episode psychosis to that in healthy controls and assess the relationship of GABA density in the vmPFC to the severity of psychotic symptoms.

Methods

Single-voxel ¹H-MRS was used to assess the concentration of GABA and other metabolites in the vmPFC of 22 patients with first-episode psychosis (10 with schizophrenia and 12 with schizophreniform disorder) and 23 healthy controls. Thirteen of the 22 patients were drug-naïve and 9 had used antipsychotic medication for less than 3 days. The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the severity of psychotic symptoms in the patient group.

Results

The mean (sd) GABA density in the vmPFC was significantly higher in patients than in controls (2.28 [0.54] v. 1.93 [0.32] mM, t=2.62, p=0.012). The densities of other metabolites – including N-acetylaspartic acid (NAA), glutamic acid (GLU), and glutamine (GLN) – were not significantly different between patients and controls. Among the patients, GABA density in the vmPFC was not significantly correlated with PANSS total score or with any of the three PANSS subscale scores for positive symptoms, negative symptoms, and general psychopathology. GABA concentration was not associated with the duration of illness, but it was significantly correlated with patient age (r=0.47, p=0.026).

Conclusion

Elevation of GABA density in the vmPFC of patients with first-episode psychosis confirms that this abnormality is independent of medication use. The failure to find a correlation of GABA density in the vmPFC with the severity of psychotic symptoms needs to be confirmed in larger studies, but it suggests that there are several intervening steps between brain pathology and clinical symptoms.     

A case of bronchial infection of Wangiella dermatitidis]

A 81-year-old woman was admitted to our hospital because of bloody sputum. Chest radiograph showed an enhanced right pulmonary hilum shadow. Computed tomography (CT) revealed localized bronchiectasis of the right lower lung and a nodule protruding into the bronchus. A parenchymal shadow was also seen distal to the nodule. Transbronchial biopsy revealed a cluster of yeast-like fungi and the bronchial lavage culture showed several olive-black colored colonies on Sabouraud agar. Before culture, we empirically administered fluconazole (400 mg/day) on the assumption of candida infection based on the yeast like microscopic findings, however that was not appropriate. Substitution by itraconazole (200 mg/day) made a slight improvement of the shadow on CT. Later polymerase chain reaction of specimens taken by TBLB identified the olive-black fungus as Wangiella dermatitidis. W. dermatitidis is a dematicious fungus sometimes causing tinea nigra or subcutaneous infection. In compromised patients, it causes phaeohyphomycosis especially in the central nerve system. In cystic fibrosis patients, this fungus is recognized to colonize the respiratory tract and rarely causes pneumonia. This case had no previous immunosuppressing disease, except for localized bronchiectasis which was found by CT on admission. We think this is a very rare W. dermatitidis infection case showing a nodular lesion in an immunocompetent patient.     

A case of pneumonia due to Mycoplasma pneumoniae accompanying high adenosine deaminase activity in pleural effusion]

We experienced a 5-year-old male case of Mycoplasma pneumoniae pneumonia accompanying Adenosine Deaminase (ADA) activity in pleural effusion. Chest roentgenograms revealed the infiltration in the left upper lung field and the left pleural effusion. In serum, the M. pneumoniae CF titer increased to 1:512. The pleural effusion was yellowish in color, with a specific gravity of 1.030, protein 3.7 g/dl, glucose 101 g/dl, and ADA 50 IU/l. Pleural effusion accompanying M. pneumoniae pneumonia is rare, and the high ADA activity in this case has been reported only in one other case. This is a report of a high activity of ADA in the pleural fluid by M. pneumoniae pneumonia.     

The WHOMEN’s Scale (Women’s HAART Optimism Monitoring and EvaluatioN Scale v.1) and the Association with Fertility Intentions and Sexual Behaviours Among HIV-Positive Women in Uganda

The objective of this study was to develop a reliable HAART optimism scale among HIV-positive women in Uganda and to test the scale’s validity against measures of fertility intentions, sexual activity, and unprotected sexual intercourse. We used cross-sectional survey data of 540 women (18–50 years) attending Mbarara University’s HIV clinic in Uganda. Women were asked how much they agreed or disagreed with 23 statements about HAART. Data were subjected to a principal components and factor analyses. Subsequently, we tested the association between the scale and fertility intentions and sexual behaviour using Wilcoxon rank sum test. Factor analysis yielded three factors, one of which was an eight-item HAART optimism scale with moderately high internal consistency (α = 0.70). Women who reported that they intended to have (more) children had significantly higher HAART optimism scores (median = 13.5 [IQR: 12–16]) than women who did not intend to have (more) children (median = 10.5 [IQR: 8–12]; P < 0.0001). Similarly, women who were sexually active and who reported practicing unprotected sexual intercourse had significantly higher HAART optimism scores than women who were sexually abstinent or who practiced protected sexual intercourse. Our reliable and valid scale, termed the Women’s HAART Optimism Monitoring and EvaluatioN scale (WHOMEN’s scale), may be valuable to broader studies investigating the role of HAART optimism on reproductive intentions and sexual behaviours of HIV-positive women in high HIV prevalence settings.     

Responding to Her Question: A Review of the Influence of Pregnancy on HIV Disease Progression in the Context of Expanded Access to HAART in Sub-Saharan Africa

In 2007, sub-Saharan Africa was home to over half of all women living with HIV. The vast majority of these women are of reproductive age, which raises concerns about the high incidence of pregnancy. As access to antiretroviral treatment is rapidly scaled up, two important questions must be answered: (1) Does pregnancy impact HIV disease progression?; (2) Does pregnancy modify the highly active antiretroviral therapy (HAART) response on HIV disease progression? A systematic review of the biomedical literature was conducted and seven relevant studies were identified. To date, it appears that there is no effect of pregnancy on HIV disease progression. Furthermore, initial studies in high-income countries suggest that pregnancy may positively modify the HAART response. These findings, however, must be interpreted with caution as it remains unclear how other factors, such as adherence, may influence the relationship between pregnancy, HIV disease progression, and HAART.     

Antiretroviral therapy is associated with increased fertility desire, but not pregnancy or live birth, among HIV+ women in an early HIV treatment program in rural Uganda

To assess the association between antiretroviral therapy (ART) and fertility history and desire among HIV-positive Ugandan women, we conducted a cross-sectional study among HIV-positive Ugandan women aged 18-50 years who attended an HIV clinic at Mbarara University in western Uganda between November 1, 2005 and June 6, 2006. Of 538 women approached, 501 were enrolled. ART use was associated with increased odds of fertility desire (AOR 2.99, 95% CI 1.38-6.28), and decreased odds of pregnancy (AOR 0.56, 95% CI 0.33-0.95) and live birth (AOR 0.30, 95% CI 0.13-0.66). ART was associated with an increase in fertility desire, but was not associated with an increase in fertility. Additional studies will be needed to determine if this greater fertility desire among ART-treated women leads to an increase in fertility as ART use expands.     

The WHOMEN’s Scale (Women’s HAART Optimism Monitoring and EvaluatioN Scale v.1) and the Association with Fertility Intentions and Sexual Behaviours Among HIV-Positive Women in Uganda

The objective of this study was to develop a reliable HAART optimism scale among HIV-positive women in Uganda and to test the scale’s validity against measures of fertility intentions, sexual activity, and unprotected sexual intercourse. We used cross-sectional survey data of 540 women (18–50 years) attending Mbarara University’s HIV clinic in Uganda. Women were asked how much they agreed or disagreed with 23 statements about HAART. Data were subjected to a principal components and factor analyses. Subsequently, we tested the association between the scale and fertility intentions and sexual behaviour using Wilcoxon rank sum test. Factor analysis yielded three factors, one of which was an eight-item HAART optimism scale with moderately high internal consistency (α = 0.70). Women who reported that they intended to have (more) children had significantly higher HAART optimism scores (median = 13.5 [IQR: 12–16]) than women who did not intend to have (more) children (median = 10.5 [IQR: 8–12]; P < 0.0001). Similarly, women who were sexually active and who reported practicing unprotected sexual intercourse had significantly higher HAART optimism scores than women who were sexually abstinent or who practiced protected sexual intercourse. Our reliable and valid scale, termed the Women’s HAART Optimism Monitoring and EvaluatioN scale (WHOMEN’s scale), may be valuable to broader studies investigating the role of HAART optimism on reproductive intentions and sexual behaviours of HIV-positive women in high HIV prevalence settings.