Genetic polymorphisms in dopamine-related genes and smoking cessation in women: a prospective cohort study

Background  

Genes involved in dopaminergic neurotransmission have been suggested as candidates for involvement in smoking behavior. We hypothesized that alleles associated with reduced dopaminergic neurotransmission would be more common in continuing smokers than among women who quit smoking.     

Thyrotropin and prolactin responses to ECT in schizophrenia and depression

Thyroid stimulating hormone (TSH) and prolactin (PRL) plasma levels were studied during electroconvulsive therapy (ECT) in five schizophrenic patients in a simulated ECT (SECT) controlled experimental design. The data were compared to those obtained from a group of 10 depressed patients treated with ECT. In the schizophrenic group, both PRL and TSH increased significantly during ECT compared to SECT, as they did in the depressive group during ECT. Thus, the hormonal TSH and PRL profile during ECT is similar in schizophrenia and depression. It is concluded that the changes in TSH and PRL induced by ECT are specifically linked to the current or the seizure, and are not related to the type of psychopathology.     

Autoradiographic localization of beta-adrenoceptors in pig lung using [125I]-iodocyanopindolol.

The binding of the beta-adrenoceptor radioligand [125I]-iodocyanopindolol (I-CYP) has been studied in pig lung parenchyma and the distribution of binding sites visualised by light microscopic autoradiography. I-CYP binding was saturable (maximum binding capacity Bmax = 51 +/- 3 fmol mg-1 protein), involving sites with high affinity (dissociation constant KD = 73 +/- 10 pM). Specific I-CYP binding was displaceable both by beta-adrenoceptor agonists ((-)-isoprenaline greater than (-)-adrenaline greater than (+/-)-fenoterol greater than (-)-noradrenaline greater than (+)-isoprenaline greater than (+/-)-RO363) and antagonists ((+/-)-propranolol greater than ICI-118551 greater than atenolol), indicating a predominance of beta 2-adrenoceptors. Further analysis showed that displacement data for the beta 1-selective antagonist atenolol and the beta 2-selective antagonist ICI-118551 were fitted best to a 2 binding site model and that both beta 1- and beta 2-adrenoceptors were present in pig lung in the ratio 28:72 respectively. Autoradiographic grains were localized over tissue and were most dense over alveolar walls greater than vascular endothelium greater than vascular smooth muscle greater than bronchial smooth muscle = bronchial epithelium. Atenolol (10(-5) M) caused a 31% reduction in specific grain density over alveolar wall tissue, while a 10 fold lower concentration of ICI-118551 (10(-6) M) caused a 50% decrease. These results are consistent with binding data in pig lung parenchyma demonstrating a mixed population of beta-adrenoceptors with a predominance of the beta 2 subtype.(ABSTRACT TRUNCATED AT 250 WORDS)     

A murine cytomegalovirus-neutralizing monoclonal antibody exhibits autoreactivity and induces tissue damage in vivo.

The autoreactivity of murine cytomegalovirus (MCMV)-neutralizing monoclonal antibody (mAb) AC1 was examined in vitro and in vivo. Both mAb AC1 and a human antiserum reactive with U1-small nuclear ribonucleoprotein (U1-snRNP) stained uninfected mouse embryo fibroblasts (MEF) in a speckled nuclear pattern and reacted with 70,000 molecular weight (MW) MEF nuclear antigens by immunoblotting, suggesting that mAb AC1 cross-reacted with the 70,000 MW component of U1-snRNP. However, only mAb AC1 cross-reacted with an additional epithelial cytoplasmic autoantigen present in cultured HEp2 cells. On tissue sections from uninfected mice, mAb AC1 predominantly reacted with a component of central and peripheral nervous systems, although cross-reactivity with the stratum spinosum of the skin and the outer sheath of hair follicles was also observed. Immunoblotting revealed that mAb AC1 reacted with phosphorylated epitopes present on a 98,000 MW MCMV structural protein and the 200,000 MW mouse neurofilament protein (NFP). Treatment of uninfected mice with mAb AC1 resulted in a severe interstitial pneumonia with greatly thickened and congested alveolar septa. Severe oedema of the hypodermis and a mild mesangial proliferative glomerulonephritis were also observed. These results demonstrate that a mAb reacting with a MCMV structural phosphoprotein which can protect mice against the dissemination of MCMV, can also promote the development of autoimmune disease. Therefore, the production of such cross-reactive antibodies may be an important mechanism in the development of autoimmunity following viral infection.     

Advanced primary breast cancer: assessment at mammography of response to induction chemotherapy

The response to induction chemotherapy is an important prognostic factor in patients with nonmetastatic, locally advanced breast carcinomas. Assessment at mammography of the response of 60 breast cancers in 59 women was performed between 1974 and 1986. Responses were excellent in 13 tumors, moderate in 34, and poor in 13 (excellent moderate = 78%). Assessment of response of discrete masses in a fatty breast was easiest; assessment of response of tumor areas that were poorly defined-such as a focal area of architectural distortion or mass in dense breast parenchyma-was more difficult. Of 17 patients with excellent pathologic responses-that is, minimal or no residual tumor-15 (88%) had complete responses (no residual tumor) as determined with mammography, physical examination, or both. Mammography provides information complementary to physical examination and is essential in the accurate assessment of the response to chemotherapy of locally advanced breast cancer.     

The effect of inhaled budesonide on adrenal and growth suppression in asthmatic children.

The present authors evaluated adrenal reserve in asthmatic children on long-term inhaled corticosteroids and whether possible adrenal suppression could be predicted by growth retardation. Low-dose synacthen test (0.5 microg x 1.73 m(-2)) was performed in 72 asthmatic children with a median age of 9.4 (range 4.2-15.7) yrs on long-term treatment (median 18 (range 6-84) months) with low-to-moderate doses (median 363 (range 127-1012) microg x m(-2)) of inhaled budesonide, as well as in 30 controls. Adrenal suppression was considered as a peak serum cortisol <495 nmol x L(-1). The current authors calculated height standard deviation score (HSDS) at the time of testing and height velocity SDS (HVSDS) in the preceding year. Mean HSDS was 0.06+/-1.3 and HVSDS was -0.9+/-2.3. Adrenal suppression was disclosed in 15 asthmatic children (20.8%). There were no differences in HSDS and HVSDS between children with and without adrenal suppression. There was no correlation between peak cortisol response and dose or duration of treatment. However, a positive relationship between HVSDS and duration of treatment was noted. These data suggest that long-term treatment of asthmatic children with low and moderate doses of inhaled budesonide may result in mild adrenal suppression that cannot be predicted by growth deceleration. The negative influence of inhaled corticosteroids on growth becomes less the longer the duration of treatment.     

Hyperhomocysteinemia and hypercoagulable state in carotid plaque evolution. Novel risk factors or coincidental risk predictors?

AIM: The majority of patients with carotid occlusive disease (COD) have one or more of the conventional risk factors of atherosclerosis. In addition, hyperhomocysteinemia (HHCY) and hypercoagulable state (HCGS) are increasingly recognized as potentially 'novel' risk factors. The aim of this study was to determine the role of these factors in carotid plaque evolution and clinical manifestation of COD. METHODS: Between September 2003 and 2005, 153 patients were admitted in our Department with clinical and duplex ultrasound evidence of severe (>70%) COD as operative candidates and 33 patients with evidence of moderate (50-69%) stenosis included in the protocol of conservative treatment and lifelong observation. Conventional risk factors of atherosclerotic disease and plasma levels of homocysteine (HCY), fibrinogen (FBG), protein C (PC), protein S, antithrombin III and activated protein C resistance were recorded in all patients. The degree of carotid stenosis was measured in a carotid angiogram following North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria for all operative candidates. Angiographic workup revealed 147 carotid stenoses >70% and 16 internal carotid occlusions in 82 symptomatic and 52 asymptomatic patients, while in 19 patients the carotid stenosis was moderate (50-69%) and these patients included in the conservative treatment group. The study of the 'novel' and conventional risk factors was performed with univariate and multivariate statistical analysis as well as with correlational analysis of HCY and the other risk factors between patients with severe or moderate COD and between symptomatic and asymptomatic patients with carotid stenosis >70%. RESULTS: Our data showed that HHCY was a strong independent risk factor of symptomatic carotid disease >70%. In addition, the coexistence of high FBG levels and thrombophilia factor deficiency with HHCY was significantly related with the clinical manifestation of COD. CONCLUSION: HHCY and HCGS are often detected among patients with severe and symptomatic carotid stenosis. The early diagnosis and treatment of these deficiencies might be helpful for the management of COD, but their role in future clinical practice is yet to be determined.     

Screening for SNCA and LRRK2 mutations in Greek sporadic and autosomal dominant Parkinson's disease: identification of two novel LRRK2 variants

Mutations in SNCA and LRRK2 genes, encoding alpha-synuclein and leucine-rich repeat kinase 2, respectively, cause autosomal dominant Parkinson's disease (AdPD). The LRRK2 G2019S (c.6055G > A) and R1441G (c.4321C > G) mutations have also been identified in sporadic PD (sPD). We studied 55 unrelated patients with AdPD, 235 patients with sPD, and 235 healthy age- and gender-matched controls all of Greek origin. Patients with AdPD were screened for SNCA and LRRK2 mutations by direct sequencing. SNCA gene dosage analysis was also performed for AdPD using quantitative duplex polymerase chain reaction of genomic DNA. In addition, we investigated the frequency of the LRRK2 G2019S mutation in sPD. We found no missense mutations or multiplications in the SNCA gene. Here we report two novel variants, A211V (c.632C > T) and K544E (c.1630A > G) in LRRK2 gene in two patients with AdPD that was not present in controls. We identified only one patient with sPD (1/235; 0.4%) carrying the G2019S mutation. LRRK2 mutations are present in AdPD and sPD patients of Greek origin.     

Clinical evaluation of the urinary sediment after renal allotransplantation

The detection of lymphoid cells by routine examination of the urine after renal allotransplantation has proved to be a useful early indication of rejection. In a study of 36 rejection episodes, 20 (56%) were associated with a significant number of lymphocytes in the urine. The incidence was much higher when rejection occurred during the first month after operation (76%); lymphocytes were rarely found when rejection occurred after three months. The appearance of lymphocytes in the urine was of particular value for detecting rejection in patients with prolonged oliguria after transplantation.