Immunoglobulin G from Breast Cancer Patients Regulates MCF-7 Cells Migration and MMP-9 Activity by Stimulating Muscarinic Acetylcholine Receptors

Purpose

We have previously reported the expression of muscarinic acetylcholine receptors (mAChR) in human breast tumors. The activation of these receptors triggered tumor cell proliferation. Considering that invasion and metastasis is the major cause of death in cancer, we investigated the action of autoantibodies against mAChR derived from breast cancer patients in stage I (T1N0Mx-IgG) on MCF-7 cells migration and metalloproteinase-9 (MMP-9) activity. We also analyzed the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.

Methods

Immunoglobulin G (IgG) was purified by chromatography in protein G-agarose from blood samples of breast cancer patients obtained under informed consent. Migration was assayed by an in vitro wound assay. MMP-9 activity was quantified by zymography.

Results

T1N0Mx-IgG promoted tumor cell migration and increased MMP9 activity mimicking the action of the muscarinic agonist carbachol. This effect was reduced not only by the presence of atropine but also by 4-DAMP or tropicamide, antagonists for M₃ and M₄ mAChR subtypes respectively. The actions of T1N0Mx-IgG and carbachol on MCF-7 cells, involved the participation of phospholipase C/nitric oxide synthase/protein kinase C pathway.

Conclusions

IgG from breast cancer patients in stage I could be promoting tumor progression by regulating migration and MMP-9 activity in tumor cells via mAChR activation. The presence of these autoantibodies could be determining the prognosis of breast cancer in these patients.     

Measurement of transmission of vibration through the human spine using skin-mounted inertial sensors

The purpose of this study was to examine the feasibility of measuring the transmission of vibration using skin mounted inertial sensors and to assess the dynamic properties of the human spine during activities of daily living. Two inertial sensors were attached to skin overlying the first thoracic vertebra (T1) and another one over the first sacral vertebra (S1) with double sided adhesive tape. Subjects walked along a straight line, and up and down stairs at a self selected, comfortable speed. Transmissibility of vertical vibration was calculated as the ratio of the power spectral density of the acceleration signal at T1 over that at S1, over the frequency range of 0.5–12 Hz. Cross correlation and coherence of the acceleration signals between the two T1 sensors were performed to evaluate the similarity of the data after correction. Cross correlation of signals between trials was also performed to examine the repeatability of the signals. Cross correlation coefficients were found to be very high (>0.9). Inter-trial consistency of the signals of all sensors was also high (>0.9). It is concluded that skin measurement of transmission of vertical vibration is feasible with the inertial sensors and correction method presented. Different physical activities seem to elicit different frequency characteristics of vibration.     

Ileal pouch-anal anastomosis: Is preoperative anal manometry predictive of postoperative functional outcome?

PURPOSE: The aim of this study was to determine the value of preoperative anal manometry in predicting postoperative continence. METHODS: Anal manometry was performed in 73 consecutive patients before ileal pouch-anal anastomosis (IPAA) surgery (m1), before loop ileostomy closure (m2), and at a follow-up of one (m3) and two (m4) years. Mean and maximum resting and squeezing pressures were documented at each occasion. One year after surgery, pressures were correlated (r)with an incontinence score. RESULTS: A significant (P < 0.05) decrease in mean resting pressures was observed after IPAA (m1=66 mmHg; m2=42.8 mmHg), followed by a significant (P < 0.05) improvement of mean resting pressure after loop ileostomy closure (m3 = 538 mmHg; m4 = 54.7 mmHg). Mean squeezing pressures did not change (P > 0.05) at any time during the study (m1 =114 mmHg; m2 = 102.9 mmHg; m3 = 103.4 mmHg; m4 = 95.8 mmHg). There was no correlation between preoperative mean resting pressure and postoperative (mI) incontinence score. CONCLUSION: Anal manometry showed a characteristic trend in internal anal sphincter injury after IPAA followed by recovery after ileostomy closure. However, it failed to prove helpful in the prediction of clinical outcome. Thus, although this study supports the continued use of manometry in a research setting, it challenges the value of routine manometry in a clinical context.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Chicago, Illinois, May 2 to 7, 1993.Dr. Morgado was a visiting surgeon from Centro Medico, Caracas, Venezuela. He was funded, in part, by a grant from The American Society of Colon and Rectal Surgeons Research Foundation.     

Immune reconstitution syndrome in patients treated for HIV and tuberculosis in Rio de Janeiro.

We made a retrospective longitudinal study from January 2000 to January 2003 to examine cases of immune reconstitution syndrome (IRS) and its incidence rate in tuberculosis (TB)-human immunodeficiency virus (HIV) co-infected patients. The incidence rate (IR) was calculated using a Poisson regression. The confidence interval (CI) that was stipulated was 95%. IRS occurred in 10/84 HIV and TB-positive patients; nine of them were on highly active anti-retroviral therapy (HAART) during a mean of 61.7 (+/- 59) days following the introduction of antiretrovirals. Lymph-node enlargement was the sole clinical manifestation. CD4 counts were <100 cells/mm(3)in 50% of the patients, at the time of TB diagnosis. All but two patients were treated with prednisone, and recovered from TB within a mean of 91 days (+/- 30 days). One relapse of TB was observed, but there were no IRS-related deaths. The incidence rate was higher (IR=11.18; CI, 1.41-88.76) in patients that had superficial lymph node enlargement at the moment of TB diagnosis (not associated with TB), extrapulmonary TB (IR=1.97; CI, 0.44-8.79), were antiretroviral naive (IR=1.85; CI, 0.48-7.16), and CD4 counts <100 cells/mm(3) (IR=1.50; CI, 0.40-5.59), although with a wide CI. IRS was frequent in our sample, occurred more frequently in HIV-naive patients with lymph-node enlargement and extrapulmonary TB. No cases of new pulmonary lesions or worsening of pulmonary infiltrates were observed.     

Sexual behaviour and infection rates for HIV, blood-borne and sexually transmitted infections among patients attending drug treatment centres in Rio de Janeiro, Brazil

A survey was carried out in 2 drug use treatment centres (TCs) in Rio de Janeiro, Brazil, to assess risk behaviours, HIV infection and other sexually transmitted infections/blood-borne infections (STIs/BBIs). Two hundred and twenty-five drug users (195 males and 30 females) were interviewed and clinically examined, and their blood and urine were tested for STIs/BBIs. Prevalences (%) for these infections were as follows--HIV: 0.9, hepatitis B virus (HBV): 14.7, hepatitis C virus (HCV): 5.8, syphilis: 5.3, gonorrhoea/chlamydia (CT/NG): 4.7. In bivariate analyses CT/NG infection was associated with younger age (P=0.003); current genitourinary symptoms (odds ratio [OR]=6.2) and a mainly illegal source of income (OR=9.1). Hepatitis C infection was associated with a history of ever having injected any drug (OR=19.6), and with each one of the injected drugs. After multiple logistic regression, lower educational level (adjusted odds ratio [AOR]=3.70) and 'ever having injected drugs' (AOR=3.69) remained as independent risk factors for hepatitis B infection. In conclusion, TCs must implement programmes directed towards the prevention of STIs/BBIs.     

Effect of dietary hydrogenated fish oil on the plasma lipoprotein profile and on the fatty acid composition of different tissues on the rat

Dietary fatty acids are actively incorporated into membrane lipids, and fat intake can modify the composition and the biochemical activity of cellular membranes and the pattern of plasma lipoproteins. Industrial hydrogenation of polyunsaturated oils leads to the formation of isomeric trans fatty acids which are incorporated into cellular membranes when they are present in the diet. The trans fatty acid amount present in hydrogenated oils depends on the degree of hydrogenation, being high for partially hydrogenated oils and low for highly hydrogenated oils. Hydrogenated fish oil is widely used in some countries for the production of margarine and industrial fats. This study compares the fatty acid composition of plasma, erythrocytes, subcutaneous adipose tissue, and hepatic microsomal membranes and the plasma lipoprotein profile after feeding rats with a synthetic diet containing either fish oil, partially hydrogenated fish oil, or highly hydrogenated fish oil. It is observed that the tissue content of monounsaturated fatty acids increases and that the content of polyunsaturated fatty acids decreases after an increase of the degree of hydrogenation of the dietary fat. Tissues from animals fed partially hydrogenated fish oil show significant amounts of trans fatty acids only. The plasma triacylglyceride composition and the lipoprotein profile are also altered by the degree of hydrogenation of the dietary fat. Triacylglycerides decrease after highly hydrogenated fat feeding only. Total cholesterol and low-density lipoprotein cholesterol are significantly increased after partially hydrogenated fat feeding. Although no direct evidence is presented, this effect may be attributable to the high content of trans isomers of this dietary fat which nutritionally may behave as saturated fatty acids.