Search

Due to increased social awareness of allergens and population hyper-sensitization, the reported incidence of allergic reactions to food allergens has increased over the past two decades. Cow's milk proteins (CMPs) are among the most common food allergens. The aim of this study was to use proteomics techniques to investigate cow's milk allergens in both full-term human colostrum and in preterm newborns mothers where both groups showed no prior allergen detection -- in order to understand whether cows milk allergens could be a cause of sensitization established through lactation. The most relevant finding was the detection of the intact bovine alpha-S1-casein in both term and preterm colostrum. Using techniques detailed in this paper and which allowed for direct protein identification, beta-lactoglobulin was not detected in any of the colostrum samples. According to our results, bovine alpha 1 casein is considered a major cow's milk allergen, is readily secreted in human milk, and so could be considered a possible cause of sensitization in exclusively breastfed infants.

The aim of this study was to evaluate the hypothalamic-pituitary-thyroid (HPT) axis function in patients suffering from lung cancer. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), free thyroxine (FT4), interleukin (IL)-2, and melatonin serum levels were measured in blood samples collected every 4 hours for 24 hours from 11 healthy participants (H; ages 35-53 years) and 9 patients suffering from non-small-cell lung cancer (C; ages 43-63 years). Relationships between hormone levels overall and over time of day were evaluated within and among groups. A prominent circadian rhythm with peaks near midnight was present for TSH and melatonin serum levels in both H and C, indicating similar synchronization of the main body clock to the 24-hour environmental light-dark cycle. As regards 24-hour means in H and C, TSH was lower in C, whereas TRH, FT4, and IL-2 were higher in C, with no difference in melatonin levels. Simple linear regression, FT4 versus TRH, showed a positive correlation in H and a negative correlation in C, whereas FT4 versus TSH showed a negative correlation in both groups. For FT4 versus IL-2, a negative correlation was found in C but not for H, whereas TSH versus TRH showed no correlation for either group. Both groups were found to be similarly synchronized to the 24-hour sleep-wake schedule, but HPT axis function was altered in patients suffering from lung cancer. When compared with healthy controls, cancer patients showed modifications of hormone serum levels overall and a negative correlation between individual TRH and FT4 levels.

Alterations in hormone secretion and cytokine levels have been evidenced in many neoplastic diseases. In this study we have evaluated the circadian profile of growth hormone (GH), insulin-like growth factor-1 (IGF-1), interleukin-2 (IL2), melatonin (MEL) and cortisol (COR) serum levels in non-small cell lung cancer patients. Blood was sampled every 4 h for 24 h in 11 healthy (H) men (ages 35-53 years) and 9 men with stage 2, 3 or 4 non-small cell lung cancer (C) (ages 43-63 years). Serum GH, total IGF1, IL2, MEL and COR were measured and examined for group differences, trends, and rhythm characteristics. 24-h means were significantly higher in C234 vs H for GH, GH/IGF1, IL2 and COR, and lower for IGF1, but IL2 and COR were not different for C23 vs H. A linear regression across 4 groups (H, C2, C3, C4) found a positive trend for COR, GH, GH/IGF1 and IL2, and a negative trend for IGF1. A linear regression run between the 24-h mean levels of GH, IGF1, COR, MEL and IL2 in healthy subjects evidenced a statistically significant positive trend between MEL and GH (R = 0.281, p = 0.022) and in cancer patients showed a statistically significant negative trend between GH and IGF1 (R = 0.332, p = 0.01), COR and IGF1 (R=0.430, p=0.001), and a statistically significant positive trend between the 24-h mean of COR and GH (R = 0.304, p = 0.02). Rhythms in MEL and COR (peaks near 01:00h and 08:00h, respectively) indicated identical synchronization to the light-dark cycle for both groups. A circadian rhythm was detected in GH and GH/IGF1 for C23 and H, with IGF1 and IL2 non-rhythmic in any group. In conclusion, an increasing trend and progressive loss of circadian rhythmicity in GH and GH/IGF1, an increasing trend in cortisol and IL2, and a decreasing trend in IGF1 in C, reflect a complex chain of events that could be involved in progression of neoplastic disease. A therapeutic strategy needs to take into account circadian patterns and complex interactions of the multiple functions that characterize the hormone and cytokine levels in the frame cancer progression.

Milk fat globule membrane (MFGM) proteins constitute a milk fraction currently of great interest, as they appear to significantly contribute to milk protective role. We investigated these proteins in human preterm colostrum and milk. For the former we found a peculiar 2-DE pattern, with a spot concentration at low molecular weight, which mass spectrometry analysis showed to be fragments belonging to some MFGM proteins with a well-known biological and especially immunological role: lactadherin, membrane-associated lactoferrin, butyrophilin, clusterin and heavy-chain immunoglobulin. Since we were able to rule out protease activity after specimen collection, we hypothesize the localization of the proteolytic enzymes in the alveolar cell membranes of the mammary gland. This mechanism is probably under hormonal control and the unexpected advent of preterm delivery would not allow hormonal conditions typical of lactation to occur immediately, causing a delay in enzymatic inhibition. This hypothesis is supported by some of our results, picturing a peculiar transient phenomenon of adaptation of the mammary-gland-membrane proteins after preterm delivery. Further studies will be required to verify whether the presence of protein fragments exerts a specific biological and immuno-defensive role in preterm infants, thus adding evidence to the outstanding biological role and benefits of mother's own milk in feeding preterm infants.

The benefits of human milk have been confirmed for preterm infants, due to its nutritional aspects and to its biologically active compounds. Oligosaccharides play an emerging leading role among these compounds. Mother's milk can sometimes be lacking for preterm infants; pasteurized donor milk represents therefore an important alternative. The aim of this study is to evaluate the effects of Holder pasteurization on the concentration and pattern of oligosaccharides in preterm human milk. Our results indicate that pasteurization does not affect the concentration or pattern of analyzed oligosaccharides.

This independent, population-based surveillance study monitored the efficacy and safety of interferon beta (IFNbeta) products in 1033 patients with relapsing-remitting multiple sclerosis (RRMS) from 15 centres in Italy. Relapses, Expanded Disability Status Scale (EDSS) scores, and adverse events were evaluated for up to 24 months. Data of patients with a baseline EDSS score < or = 3.5 are reported. The proportions of relapse-free patients were similar among the groups at 12 and 24 months (P = 0.10). IFNbeta products produced significant reductions from baseline in relapse rates at 12 and 24 months (P < 0.001), with no differences among treatments (P = 0.2). There were no significant differences in mean EDSS change among groups at 12 or 24 months. The IFNbeta-1b group showed a higher incidence of adverse events during the first year of treatment (P < 0.05) than IFNbeta-1a groups, and more withdrawals (10%) compared with Avonex (5%) at 24 months. IFNbeta products are equally effective in low disability RRMS, but IFNbeta-1a may have a more favorable efficacy/tolerability ratio.

The validity of serum sICAM-I levels to assess Multiple Sclerosis (MS) activity was evaluated in 49 untreated definite relapsing-remitting (RR) patients. sICAM-I levels were significantly (P = 0.0009) higher in the 'clinically active' group (No 22) than in the 'clinically inactive' (No 27), whereas no different values were found between patients with Gd-enhancing lesions at MRI (Gd-positive) (No 32) and patients without such lesions (Gd-negative) (No 17) independently of their clinical activity. Among the 'clinically active' MS, the Gd-positive (No 16) subgroup showed significant (P < 0.05) lower sICAM-I levels when compared to the Gd-negative (No 6) subgroup, but higher (P = 0.009) than those of the 'clinically inactive Gd-positive' (No 16) patients. The sICAM-I levels did not differ between the two 'clinically inactive' subgroups Gd-positive (No 16) and Gd-negative (No 11). Finally the clinically active Gd-negative (No 6) showed sICAM-I levels higher (P = 0.002) than the clinically inactive Gd-negative (No 11). The specificity of high serum sICAM-I levels (above M +/- 2 s.d. of control values) to assess the disease activity in MS resulted higher (100%) using clinical than Gd-MRI activity (76%) as gold standard. The changes induced by 1 year recombinant Interferon-beta-Ib (rIFN beta-Ib) treatment on sICAM-I serum levels were also longitudinally investigated in 36 of the 49 RR MS. sICAM-I levels at baseline significantly increased in the first 2 months (baseline vs 1st month P < 0.0001 and 1st vs 2nd month P = 0.02), persisted at high levels without any significant change after 3 months, showed a temporary decrease at 6 months, then significantly increased again at 9 and 12 months. Fourteen patients experienced relapses, with a total of 20 relapses, during the whole treatment duration. The mean relapse/rate and the frequency of patients with Gd-positive MRI scans resulted significantly higher in the first semester compared to the second semester of treatment. This study adds further insights into the validity of serum sICAM-I to assess disease activity in MS and on the immunomodulatory properties of rIFN beta-Ib.

Serum and cerebrospinal fluid (CSF) soluble intercellular adhesion molecule-I (ICAM-I) levels were evaluated (ELISA) in 22 untreated and 13 corticosteroid-treated active relapsing remitting (RR) Multiple Sclerosis (MS), in 10 untreated and 10 corticosteroid-treated Guillain-Barré syndrome (GBS) and in 17 non-inflammatory neurological diseases (NIND). Twenty-eight clinically inactive RR MS were assayed for serum sICAM-I before and after 3 months treatment of 8 MIU rIFN beta-Ib taken s.c. every other day. High sICAM-I serum levels above the NIND values were found in untreated clinically active MS and in untreated GBS (P < 0.05) but not in the untreated clinically inactive MS group. The active MS group showed significantly (P = 0.0001) higher sICAM-I serum levels if compared to the inactive group. Corticosteroid-treated active MS and GBS patients showed lower (P < 0.05) serum sICAM-I levels than the corresponding untreated groups. Serum sICAM-I levels after 3 months of rIFN beta-Ib treatment (P < 0.0001, paired t-test) resulted increased compared to pretreatment values in MS. The mean values of CSF/serum sICAM-I:CSF/serum Albumin ratios (sICAM-I Index) in active untreated MS patients were higher compared to NIND (P < 0.005) and to corticosteroid-treated MS group (P = 0.01). sICAM Index values in GBS did not differ from those in NIND. The results seem to suggest potential roles for serum sICAM-I in downregulating the ongoing inflammatory response at the blood-brain barrier level and for CSF sICAM-I in the maintenance of a central nervous system local immune response.

Aims and Background: Salvage treatment of advanced colorectal cancer patients has not been well defined as yet, and new potentially active drugs or combinations should be evaluated for these situations., Methods: From February 1993 to September 1993, the combination of carboplatin (CBDCA) and etoposide (VP-16), both as 100 mg/m2 for three consecutive days, was administered to 17 colorectal cancer patients who had been previously subjected to FA-FU combination chemotherapy. The CBDCA + VP-16 treatment was repeated every 3 weeks. A total of 58 cycles was administered, and 16 patients were evaluable for response., Results: There was no objective response, but 2 stable diseases and 14 progressive diseases were observed. Toxicity was mild, with no WHO 3-4 grade toxicity., Conclusion: This combination chemotherapy was judged ineffective for pretreated colorectal cancer patients.

Xeroradiography, a method of X-ray imaging based upon selenium photoconductivity, was used for the study of experimental osteosarcoma induced by MSV-M virus in rats. Due to the peculiar features of xeroradiographic image (enhancement of details and lowering of the overall contrast) good pictures of osseous structures together with soft tissues were obtained even in very young animals. Serially perfomred xeroradiographies gave a permanent representation of tumor evolution with time. Advantages and drawbacks of this method are discussed, particularly with respect to radiation dosage. Xeroradiography is proposed for the study of the response to antiblastic chemotherapy of experimental bone tumors.

In rats repeatedly treated subcutaneously as infants with adriamycin in 2 cycles of 4 treatments each, the induction of ocular and dental abnormalities and tumors was studied. Cataracts appeared from 18 to 26 days in 80% of CD rats treated with 1.15 mg/kg/day of adriamycin and from 28 to 104 days in 55% of Wistar-Lewis rats given 0.75 mg/kg/day adriamycin. Abnormal growth of incisors was observed in 30% of the CD rats and in 44% of the Wistar-Lewis rats. At lower doses, no such abnormalities were found. At about 1 year after treatment, 100% of the CD rats treated with 0.75 mg/kg/day adriamycin and about 60% of the Wistar-Lewis rats treated with 0.75 and 0.5 mg/kg/day adriamycin developed tumors, which were histologically classified.

4-demethoxydaunorubicin was tested against experimental mouse leukemias, in comparison with doxirubicin and daunorubicin. 4-demethoxydaunorubicin, administered ip to mice bearing ascitic L1210 or P388 leukemia was 5 times more potent than daunorubicin and 10 times more potent than doxorubicin (potency established in relation to optimal antitumor doses). At the optimal doses, 4-demethoxydaunorubicin was as active as daunorubicin and less active than doxorubicin. 4-demethoxydaunorubicin, administered iv was 8 times more potent than daunorubicin and 4-5 times more potent than doxorubicin. At the optimal doses, 4-demethoxydaunorubicin was markedly more active than daunorubicin or doxorubicin in mice injected iv with 10(5) L1210 leukemia cells (early or late leukemia) or with 10(2) Gross leukemia cells. In mice given 2 X 10(6) Gross leukemia cells iv, 4-demethoxydaunorubicin was as active as doxorubicin when treatment was given iv on days 1, 5 and 9 for 4-demethoxydaunorubicin, and on days 1, 3 and 6 for daunorubicin and doxorubicin. 4-demethoxydaunorubicin administered orally was highly active against ascitic P388 leukemia and against L1210 and Gross leukemia inoculated iv.

Two cell lines derived from a primary MSV-M-induced tumor in a BALB/c mouse were studied. One line (MS-2) was subject only to continuous tissue culture transfer (tct). After 21 tct, MS-2 cells produced progressive tumors (MS-2 tumors) in syngeneic hosts. The second cell line (MS-2T) was established by cultivation of a MS-2 tumor. The ability to produce progressive tumors decreased with increased number of tct, in both cell lines. The virus content of MS-2 and MS-2T cells was very low, as shown by uridine incorporation and electron microscopy. Immmunofluorescence tests demonstrated that antigens different from the viral MSV-M antigens were present on the cell lines, and that antigenic changes occurred with increased number of tct. Serum of mice bearing progressive MS-2 tumors reacted with MS-2T cells when these cells produced progressive tumors and did not react with MS-2 cells when they produced regressing tumors. MS-2 cells producing regressing tumors reacted with serum from mice in which the MS-2 tumor had regressed and with serum from mice immunized with MS-2T cells at late tct when they were poorly oncogenic. The antigenic changes seemed, therefore, to parallel the decrease of malignancy. A chromosomal analysis carried out on MS-2 and MS-2T cells, when both produced progressive tumors, showed a modal number of 48 and 44, respectively. MS-2T cells showed a large acrocentric chromosome. In contrast, the MS-2 cells at late tct, when they gave regressing tumors, showed a modal number of 60 and a wide range of distribution of chromosome number.

The authors report a case of renal cell carcinoma metastasis to the pancreas occurring 25 years after nephrectomy. The need for prolonged follow-up of patients is emphasized. The surgical approach is considered the best way to deal with such late metastases.

This paper describes the effect of Tween 80 on the antitumor activity and on the distribution of adriamycin in mice. The dilution of adriamycin in a 10% water solution of Tween 80 produced a significant increase of the antitumor activity in mice against ascites tumors (L 1210 leukemia), disseminated leukemias (transplanted leukemias originally induced by Gross leukemai virus and Moloney leukemia virus), and solid tumors (Sarcoma 180, MS-2 sarcoma). In all these experiments the drug was administered i.v., according to different schedules. Higher antitumor activity at the optimal dose and an increase of activity at lower doses were observed in different experimental systems. Toxicity was also slightly enhanced. Tissue distribution was studied in normal mice and in tumor-bearing mice (Gross leukemia and MS-2 sarcoma). In animals give i.v. adriamycin diluted in 10% Tween 80 there was a higher drug concentration in spleen, lung and kidney than there was in mice given the drug in a water solution. In all the other organs examined (heart, liver, small intestine) and in the MS-2 tumor tissue, no significant increase was observed. In L1210 leukemia-bearing mice, i.p. treatment with adriamycin diluted in 10% Tween 80 resulted in a significantly higher toxicity than that which resulted from treatment with adriamycin in a wa ter solution; no increase of antitumor activity was observed.