Mammaglobin: a candidate diagnostic marker for breast cancer

Mammaglobin, known for its mammary tissue specificity, has been discussed as a promising diagnostic marker in breast cancer for almost 10 years. In particular, the application of mammaglobin RT-PCR to detect disseminated breast cancer cells has been reported. More than 25 publications evaluate the detection of mammaglobin mRNA in lymph node, blood, and bone marrow specimens of breast cancer patients. Recently, structural details about the mammaglobin complex have been discovered, and these findings can be implemented to optimize detection of the secreted protein. This review summarizes the findings of almost 50 published studies and the current knowledge about the diagnostic utility of mammaglobin.     

The dioxin-like pollutant PCB 126 (3,3',4,4',5-pentachlorobiphenyl) affects risk factors for cardiovascular disease in female rats

Epidemiological studies suggest that exposure to persistent organic pollutants such as organochlorines might induce cardiovascular disorders and diabetes. Some of these organochlorines, such as dioxins and some dioxin-like PCBs, have been characterised as anti-estrogenic due to their inhibition of estrogenic-induced responses. In the present pilot study, 40 female rats were subjected to either exposure to the dioxin-like 3,3′,4,4′,5-pentachlorobiphenyl (PCB 126) or vehicle, as well as ovariectomy (OVX) or sham operation in a 2×2 factorial design over 12 weeks to explore potential interactions between estrogen status and PCB 126 exposure on cardiovascular risk factors.

PCB 126 increased heart weight and serum cholesterol levels in both groups. PCB 126 increased blood pressure in the sham-operated animals only.

In conclusion, PCB 126 exposure in female rats resulted in effects on cardiovascular risk factors, such as serum cholesterol, blood pressure, and heart weight. Of these effects of PCB 126, the increase in blood pressure was dependent on estrogen status.     

Electrochemical determination of Cephalothin antibiotic by adsorptive stripping voltammetric technique

A sensitive and reliable stripping voltammetric method was developed to determine Cephalothin antibiotic drug. This method is based on the adsorptive accumulation of the drug at a hanging mercury drop electrode and then a negative sweep was initiated, which yield a well defined cathodic peak at −625 mV versus Ag/AgCl reference electrode. To achieve high sensitivity, various experimental and instrumental variables were investigated such as supporting electrolyte, pH, accumulation time and potential, drug concentration, scan rate, convection rate and working electrode area. The monitored adsorptive current was directly proportional to the concentration of Cephalothin and it shows a linear response in the range from 4×10⁻⁷ to 1.2×10⁻⁶ mol l⁻¹ (correlation coefficient=0.9995) and the detection limit (S/N=3) is 3.3×10⁻⁹ mol l⁻¹ at an accumulation time of 3 min. The developed AdSV procedure shows a good reproducibility, the relative standard deviation R.S.D.% (n=10) at a concentration level of 5×10⁻⁷ mol l⁻¹ was 0.94%. Possible interferences by other pharmaceutical drugs and surfactants have been also evaluated. The applicability of this approach was illustrated by the determination of Cephalothin in pharmaceutical preparation and biological fluids such as serum and urine.     

Serum Fructosamine and Colorectal Adenomas

The relationship of glucose in the blood with colorectal adenoma or cancer is not clear. Fructosamine, equivalent to total serum glycated proteins, is a marker of blood glucose levels in the previous 3 weeks. We evaluated in a case-control study the association between fructosamine and colorectal adenoma, a precursor of colorectal cancer. Cases were subjects with the first occurrence of one or more histologically confirmed colorectal adenomatous polyps removed after a complete colonoscopy (153 cases), and controls were subjects with normal colonoscopy performed in the same endoscopy units during the same period (84 controls). Serum fructosamine was measured by a colorimetric method. Unconditional multiple logistic regression was used for statistical analysis. We found that in non-diabetic subjects the risk of colorectal adenoma increased with the level of fructosamine, and the odds ratio of colorectal adenoma in subjects with fructosamine levels higher than the median (270 microg/100 ml), in comparison with subjects with fructosamine lower than the median, was 2.3 (95% CI: 1.1-4.8). The risk of colorectal adenoma increased also with increasing levels of serum triglycerides and cholesterol, and decreased with increasing levels of fasting serum insulin. The results of this study show that the risk of colorectal adenoma increases with the level of fructosamine, an indicator of the level of glucose in the blood more sensitive to foods with a high glycemic index.     

Serum IgG levels to bovine insulin in type I diabetes mellitus

Objectives: This study was undertaken to determine humoral immune response to bovine insulin in Iranian children with type 1 diabetes mellitus.Methods: Serum samples were taken from 93 children aged 4–17 years with type I diabetes mellitus from two centers in Iran (the Iranian Association of Diabetes in Tehran and Center for Diabetes Research in Hamedan), 17 apparently healthy siblings of the diabetic patients (related controls), 28 apparently healthy age- and sex-matched controls (unrelated controls), 14 patients aged 11–15 years with auto-immune thyroiditis, and 45 patients with type II diabetes (aged 44–68 years). Samples were then examined for specific IgG to bovine insulin by enzyme-linked immunosorbent assay (ELISA). A questionnaire on medical history, duration of exclusive and non-exclusive breast feeding and daily intake of dairy products was completed before bleeding.Results: Duration of exclusive and non-exclusive breast-feeding showed no significant difference between patients with type I diabetes, related and unrelated controls and thyroid patients. Diabetic children, however, had significantly higher serum levels of anti-bovine insulin IgG than did unrelated and related healthy controls and patients with type II diabetes (P < 0.01). There was no significant difference between healthy siblings of diabetic children and unrelated controls. In type I diabetic patients and their healthy siblings, serum levels of IgG to bovine insulin were inversely correlated with the duration of non-exclusive breast feeding (r_s= -0.37, P= 0.016 and r_s -0.53, P= 0.049, respectively). There was no con-elation between serum levels of IgG to bovine insulin with daily intake of dairy products. Bovine insulin cross-reacted with human insulin as judged by ELISA inhibition assay.Conclusion: The emergence of anti-insulin antibodies in Iranian patients with type I DM, which is associated with the duration of breast-feeding is less likely to be due to early exposure of infants with the proteins found in cow’s milk. One speculation could be that the production of antibodies to insulin in type I diabetes may just be a physiologic response (probably to increase the half-life of the circulating insulin). The importance of anti-insulin antibodies in type I diabetes mellitus needs further studies.     

Serum ferritin and transferrin receptor concentrations during the transition from adolescence to adulthood in a healthy Swedish population

Aim: As part of a longitudinal nutrition study of adolescents, changes in serum ferritin (s-Ft), serum transferrin receptors (s-TfR) and the TfR/Ft ratio from 15 to 21 y of age were studied in randomly selected Swedish adolescents. Methods: Blood samples from 60 males and 66 females were drawn at 15, 17 and 21 y of age. Results: In males, median s-Ft increased significantly from 33 mgrg l-1 at 15 y to 96 mgrg l-1 at 21 y, and in females, after a non-significant decrease at 17 y, from 27 at 15 y to 34mgrg l-1 at 21 y. Between 15 and 17 y, s-TfR increased significantly, in males from 5.9 to 7.7 mgrg l-1, and in females from 5.2 to 7.6 mgrg l-1, whereas s-TfR decreased significantly in both genders between 17 and 21 y. The log (TfR/Ft) ratio did not change in males between 15 and 17 y, but decreased significantly from 2.2plusmn0.3 to 1.8plusmn0.3 by the age of 21 y. In females, the TfR/Ft ratio increased significantly between 15 and 17 y, whereas a significant decrease was found by the age of 21 y. S-Ft lt12mgrg l-1 at 15, 17 and 21 y was 3, 2 and 2% in males, and in females 18, 26 and 21%, respectively. Conclusion: This study shows an increase in s-Ft and a decline in s-TfR in males, indicating increased iron stores. In females, s-Ft did not increase significantly, whereas s-TfR and the TfR/ Ft ratio decreased between 17 and 21 y, indicating that cellular iron needs were met.     

Serum interferon inhibitor declines in patients with HIV-1 infection after a change in antiretroviral therapy

An inhibitor of interferon antiviral activity, which is absent in healthy HIV-seronegative persons, was detected in the sera of all 29 HIV-seropositive study participants. The relationship of the level of interferon inhibitor to CD4 count and HIV-RNA copy number was statistically significant in distinct models. Levels of interferon inhibitor declined by an average of 41-60% in patients who underwent a change in anti-retroviral therapy. Interferon inhibitor levels appear to decline as CD4 cell count rises and HIV-RNA levels fall. This suggests that interferon inhibitor may have a significant role in the host immune response to HIV infection.     

Serum iron level as an indicator for inflammation in dogs and cats

Iron is one of the most frequent cations in the body. Serum iron levels are probably influenced by disease. In our study we investigated serum iron levels in cases of inflammation in dogs and cats and found decreased iron level in cases of inflammation. Unfortunately, there was no correlation between the iron level and the leucocyte count, so the diagnostic use of iron is limited. Furthermore we have looked at which diseases have a negative influence on iron level and found decreased levels in cases of renal insufficiency, anaemia and hyperadrenocorticism. We compared our results with reports on human diseases.     

Serum sialic acid in subjects with impaired glucose tolerance and in newly diagnosed type 2 diabetic patients

Several general population studies and those carried out in diabetic patients with complications have pointed to serum sialic acid as a marker of inflammation in atherosclerosis. In this study we examined whether total sialic acid (TSA) was changed in the sera of 28 newly diagnosed subjects with type 2 diabetes (type 2 DM), 47 subjects with impaired glucose tolerance (IGT) and 72 subjects with normal glucose tolerance (NGT). The associations between sialic acid and other atherosclerotic risk factors such as lipid profile, baseline diene conjugates in low-density lipoproteins (LDL-BDC) and fasting insulin were also investigated. We found a trend to TSA increase in subjects with impaired glucose tolerance and a significant increase in TSA in newly diagnosed patients with type 2 DM (2.2±0.3 vs. 1.9±0.3 mmol/l; p<0.03) when compared to subjects with NGT. Lipid profile and LDL-BDC, as a marker of circulating oxidized LDL, did not differ among glucose tolerance categories. Significant associations between total sialic acid and 2-h post-load glucose level, fasting insulin, insulin sensitivity, HDL-cholesterol and log of triglycerides were found in the examined subjects. Multiple regression analysis showed significant correlations between serum sialic acid and 2-h post-load glucose levels and insulin sensitivity. This study indicates that measurement of TSA as a marker of subclinical inflammation may be valuable as an independent parameter in identifying subjects at higher risk of developing type 2 diabetes and those who might benefit from anti-inflammatory treatment. Received: 10 May 2002 / Accepted in revised form: 15 April 2003 Correspondence to M. Gavella     

Longitudinal study of cryptococcosis in adult solid-organ transplant recipients

While studies in kidney recipients have found meningitis to be the most common clinical manifestation of cryptococcosis (Cry), it is unclear if the clinical presentation of Cry differs among various solid-organ transplant (SOT) recipients and whether the serum cryptococcal antigen (SCA) might predict the site of infection. We report the clinical manifestations and the correlation with a positive SCA among 55 consecutive SOT recipients diagnosed with Cry at the University of Pittsburgh Medical Center. These included: heart (n=13), lung (n=4), liver (n=28), kidney (n=9) and small bowel (n=1) recipients. While there were no significant differences in the manifestations of Cry in heart and lung recipients, kidney recipients had disseminated disease as the most common presentation (P=0.02). In contrast, pneumonia (P=0.003) and meningitis (P=0.02) were more frequent than disseminated disease in liver recipients. Positive SCA was higher in patients with disseminated disease and meningitis than in patients with isolated pneumonia (P=0.0001). Significant differences in the manifestations of Cry were observed among types of SOT populations. A positive SCA may be predictive of dissemination and meningitis, but it may not be sensitive for pulmonary disease.