A comparison of succinyladenylate lyase activity and serum sialic acid as markers of malignancy

A comparison was made of succinyladenylate lyase (SAMP lyase), total serum sialic (TSA), and lipid soluble serum sialic acid (LSA) as early markers of malignancy in three experimentally induced rat tumor models. Elevation of SAMP lyase in 3'-methyl-dimethylaminoazobenzene-induced hepatic tumors at 2 weeks corresponded with microscopic detection of preneoplastic lesions with elevation of LSA occurring 2 weeks later. Elevation of breast SAMP lyase concurred with macroscopic presence of dimethylbenzanthracene involved breast tumors with elevation of LSA occurring 12 weeks later. Neither colon SAMP lyase nor LSA increased in rats bearing colon tumors induced by dimethylhydrazine. The determination of TSA was not a reliable indicator of tumor presence for the three types of tumors investigated. Both SAMP lyase and LSA are very good early indicators of hepatic tumor with SAMP lyase an earlier indicator of breast tumor than LSA.     

Chronic alcohol consumption augments loss of sialic acid residues and alters erythrocyte membrane charge in type II diabetic patients

In this study, the effects of alcohol consumption on erythrocyte membrane properties in type 2 diabetic patients were investigated. Therefore, we measured total and lipid-bound sialic acid (LSA) levels, sialidase activities, and erythrocyte membrane negative charge. Three groups, including control group (n = 20), alcohol-consuming diabetic patients group (n = 14), and diabetic patients without alcohol consumption group (n = 42), were created. Plasma total sialic acid (TSA) levels of the alcohol-consuming diabetic group were elevated as compared to the healthy control and diabetic group (p < 0.001 and p < 0.01, respectively). TSA levels of the diabetic group were significantly elevated as compared to the healthy control group (p > 0.001). Plasma LSA levels of the alcohol-consuming diabetic group were higher than that in the healthy control and diabetic group (p < 0.05 and p < 0.05, respectively). LSA levels of the diabetic group were found to be high as compared to the healthy control group (p < 0.05). Plasma sialidase activities of the alcohol-consuming diabetic group and diabetic group were significantly elevated as compared to the healthy control group (p < 0.05 and p < 0.05, respectively). Sialidase activities of the alcohol-consuming diabetic group were elevated as compared to the diabetic group, but this was not statistically significant (p > 0.05). Erythrocyte membrane negativity levels of the alcohol-consuming diabetic group and diabetic group were significantly decreased (p < 0.001 and p < 0.001, respectively) as compared to the healthy control group. Erythrocyte membrane negativity levels of the alcohol-consuming diabetic group were decreased as compared to the diabetic group, but this was not statistically significant (p > 0.05). In conclusion, our results indicate that chronic alcohol consumption may augment membrane alterations in type 2 diabetic patients.     

Clinical significance of preoperative serum sialic acid levels in colorectal cancer: utility in the detection of patients at high risk of tumor recurrence

This study was conducted to evaluate the significance of preoperative serum sialic acid levels in the diagnosis and prognosis of colorectal cancer (CRC). Total sialic acid (TSA) was determined by the thiobarbituric acid method and normalized to total protein (TP). A postoperative follow-up of CRC patients classified as Dukes' stages A, B or C was performed and survival analysis was carried out to evaluate the impact of sialic acid levels on tumor recurrence. Our diagnostic studies indicate that TSA/TP is a better marker than either TSA or carcinoembryonic antigen (CEA), especially for the detection of CRC patients at an early stage. At a cutoff of 30.90 nmol/mg of protein, TSA/TP showed a sensitivity of 85% with a specificity of 97% to discriminate CRC patients from healthy donors. In survival analysis, both TSA and TSA/TP were found to be significant prognostic factors for tumor recurrence in CRC. Furthermore, TSA/TP could distinguish patients at high risk of recurrence within Dukes' stage B and in multivariate analysis it was identified as the best independent prognostic factor. According to our results, preoperative serum TSA/TP content could supply additional information to that provided by Dukes' stage about the prognosis of CRC patients.     

Serum sialic acid levels and selected mineral status in patients with type 2 diabetes mellitus

The aim of the present study was to investigate whether altered serum total sialic acid (TSA), lipid-associated sialic acid (LSA), copper (Cu), manganese (Mn), zinc (Zn), chromium (Cr), iron (Fe), and magnesium (Mg) levels had an interactive connection with diabetes and also whether they were correlated with each other in diabetic patients. Two study groups (control and type 2 diabetic subjects) were included. Two hundred patients (108 female and 92 male), diagnosed and treated for type 2 diabetes in the Yuzuncu Yil University Hospital (Van, Turkey), were selected consecutively to represent type 2 diabetic patients. Fifty healthy individuals (29 female and 21 male) served as the control group matched for age, sex, body mass index, and smoking status were selected from hospital staff and other outpatient clinics. All participants had not taken vitamin or mineral supplements for at least 2 wk before sampling. Blood samples were drawn after an overnight fasting in both groups for the determination of serum glucose, TSA, LSA, Cu, Zn, Mn, Cr, Fe, and Mg. It was found that diabetics had higher TSA, LSA, Fe, Mn, Fe/Zn, and Cu/Zn levels, and lower Zn and Mg levels than those of controls. Although, Cu levels were higher, and Cr levels were lower in total and male diabetic patients, they were not different in female diabetic patients than in controls. The Cu/Fe ratio was lower in total and female diabetic patients, but not different in male diabetic patients than controls. The Zn/Cr ratio, on the other hand, was not different in diabetics than in controls. There was only a positive correlation between Fe-Mn levels in male diabetic patients. There was a negative correlation in LSA-Mn, Fe-Cu, Cu-Fe/Zn, and Mn-Cu/Zn levels in total diabetic patients. There was a positive correlation in TSA-Cr, TSA-Mg, LSA-Cu/Fe, LSA-Zn/Cr levels, and a negative correlation in TSA-Cu/Zn, LSA-Mn, Fe-Cu, Mn-Cu, Cu-Fe/Zn, Fe-cholesterol, and Cr-cholesterol in female diabetic patients. Our results showed that TSA, LSA, and selected minerals have interactive connections with diabetes mellitus (DM). There are also many sex-related positive or negative correlations between the altered parameters in diabetic patients. These parameters might be used as diagnostic index in patients with DM.     

Tumor markers in leukemia: evaluation of serum levels of different forms of sialic acid, Regan isoenzyme and lactate dehydrogenase.

A sensitive and specific serum marker can greatly help in the early diagnosis of malignancy as well as in monitoring the treatment of cancer patients. The present work was initiated for determining serum levels of Total Sialic Acid (TSA), Lipid Bound Sialic Acid (LSA), Free Sialic Acid (FSA). Regan Isoenzyme (RI) and Lactate Dehydrogenase (LDH), so as to evaluate their value as potential tumor markers. Fifty patients with anemia and 78 patients with leukemia were studied. The leukemia group consisted of 32 cases of Acute Myeloid Leukemia (AML), 29 cases of Chronic Myeloid Leukemia (CML) and 17 cases of Acute Lymphatic Leukemia (ALL). The levels were compared with the values obtained from 88 healthy individuals. Compared to the healthy controls, all the biomarkers were significantly elevated in patients with anemia as well as in those with leukemia. However, in leukemia patients significantly higher levels of TSA, LSA, FSA and LDH were observed compared to anemia patients. TSA levels were significantly higher in AML patients compared to CML and ALL patients. LSA levels were also significantly higher in AML patients compared to ALL patients. LSA was the most sensitive (84.6%) while FSA and RI levels were the most specific (78.0%) markers for leukemia. The combined use of the markers showed increased sensitivity and specificity (100.0% and 98.0%, respectively). The study suggested that the biomarkers investigated might be used for differentiating anemic from leukemic conditions, however, more in-depth studies are indicated to assess their utility in classifying various leukemias.     

正常和异常的人精浆中甘油-3-磷酸胆碱、总唾液酸及化学元素含量的比较研究

用酶法和过碘酸 -硫代巴比妥酸法对正常男性和异常男性患者精浆甘油 3 磷酸胆碱(GPC)、总唾液酸 (TSA)量进行了测定 .通过电感耦合等离子直读光谱仪 (ICP)测定精浆中多种化学元素的含量 .结果表明 :正常男性与异常男性患者精浆中GPC的含量有显著性差异 (P <0 0 5) ;正常男性与异常男性患者精浆中TSA的含量无显著性差异 ;正常男性与异常男性患者精浆中钙、镁、磷、硒和锌元素的含量具有显著差异 ,而正常男性与异常男性患者精浆中铝、钡、铁和铅元素的含量无显著差异 .这些结果提示精浆中GPC、钙、镁、磷、硒和锌元素的含量可能与男性不育有关 ,而精浆中TSA、铝、钡、铁和铅元素与男性不育关系还需进一步探讨 .     

Tissue and serum α2-3- and α2-6-linkage specific sialylation changes in oral carcinogenesis

Increased sialylation of cell surface glycoconjugates is among the key molecular changes associated with malignant transformation and cancer progression. We investigated significance of linkage-specific sialylation changes in oral carcinogenesis. Tissue and serum levels of total sialic acid (TSA), linkage-specific sialyltransferases (ST) and sialoproteins were analyzed from patients with oral precancerous conditions (OPC) and oral cancer as well as the post-treatment follow-up blood samples of oral cancer patients. TSA levels were measured using a spectrophotometric method. The linkage-specific lectins, Sambusus nigra (SNA) and Maackia amurensis (MAM) detects α2-6- and α2-3-linked sialic acid, respectively, were used to analyze ST activity and sialoproteins. Malignant tissues showed significantly higher levels of TSA, reactivity of SNA and MAM, and α2,3-ST activity compared to the adjacent normal tissues. α2,6-ST was also higher in malignant tissues. Similarly, the marker levels were higher in precancerous tissues than their adjacent normal tissues. Serum levels of TSA, TSA/ total proteins, α2-6-sialoproteins and α2,6-ST were markedly increased in untreated oral cancer patients compared to the controls and OPC as well as responder (CR) patients. Serum levels of the markers were higher or comparable between untreated oral cancer patients and non-responders (NR). Serum levels of α2-3-sialylation were elevated in non-responders compared with the responders. Further, the observed sialylation changes in tissue and serum were found to be associated with various clinicopathological features and disease progression. Thus, the data suggest potential utility of sialylation markers in early detection, prognostication and treatment monitoring of oral cancer.     

Sialic acid and carcinoembryonic antigen (CEA) as markers of colon cancer: Preliminary report]

Tumor markers known to date are not sensitive and specific enough to detect malignant tumors. Therefore, attempts to find new markers have led to sialic acid assays in cancer patients. Serum sialic acid, CEA and ESR have been determined in 33 patients with the cancer of the colon. All patients have been divided into four groups, according to TNM cancer staging. Serum sialic acid levels have been increased by 100% of patients in groups I and IV. The most significant correlation was noted between sialic acid levels and ESR. No significant relationship between serum sialic acid and CEA have been noted. No correlation of the colon cancer stage, according to TNM staging, and sialic acid and CEA levels in the peripheral blood has been observed. It seems, however, that serum sialic acid assay may be useful auxiliary technique in the detection and monitoring of patients with colon cancer.     

桂枝茯苓胶囊对卵巢囊肿患者囊肿核摘除术后血清雌激素、AMH及LSA水平的影响

目的:探究桂枝茯苓胶囊对卵巢囊肿患者囊肿核摘除术后血清雌激素、抗苗勒氏管激素(AMH)及脂质结合唾液酸(LSA)水平的影响。方法:选择我院收治的已行囊肿核摘除术的卵巢囊肿患者39例,将其随机分为实验组及对照组。对照组18例予甲硝唑联合青霉素注射治疗;实验组21例予桂枝茯苓胶囊治疗。治疗后,对比两组的临床疗效及治疗前后血清雌激素、AMH及LSA的水平。结果:治疗后,实验组总有效率(95.2%)显著高于对照组(72.2%),差异具有统计学意义(P0.05);治疗后,两组血清雌激素、AMH水平均明显升高,血清LSA水平显著降低,差异均具有统计学意义(P0.05);与对照组比较,实验组治疗后血清雌激素、AMH较高,而LSA水平较低,差异具有统计学意义(P0.05)。结论:桂枝茯苓胶囊可以有效提高行囊肿核摘除术卵巢囊肿患者的临床疗效,这可能与其提高血清雌激素及AMH水平并降低血清LSA水平有关。     

Erythrocyte membrane bound and plasma sialic acid during aging

Sialic acid, a nine-carbon sugar, is an acetylated derivative of neuraminic acid predominantly found in vertebrates, a few higher invertebrates, and certain types of bacteria. Red blood cells (RBCs) have a net negative surface charge and this bulk charge is due to ionized sialic acid. Decreased surface charge and sialic acid content have been reported in older erythrocytes, and it is postulated that the decreased electro-negativity may be related to cell senescence. In the present study we report the RBC and plasma sialic acid content during aging in rats. Our results show a significant decrease in RBC sialic acid content and increase in plasma sialic acid as a function of rat aging. The decreased sialic acid in erythrocyte membrane with increasing rat age presents a good biomarker of the aging process. The elevated plasma sialic acid may be a manifestation of several factors including increased expression of acute phase proteins and increased damage to various organs.     

Serum Selenium,Vitamin E,and Sialic Acids Concentrations in Lambs with White Muscle Disease

The aim of this study was to determine the serum concentrations of selenium, vitamin E, and total- and lipid-bound sialic acid (LBSA) in lambs with white muscle disease (WMD) before and after treatment with a commercial preparation containing selenite and vitamin E. Fifteen lambs with WMD and ten control animals were used as research materials. Blood samples were collected from both groups before- and 1 month after treatment for Se analysis by fluorimetry, whereas vitamin E and sialic acid were measured by HPLC and spectrophotometry, respectively. Compared to controls, in the diseased animals, there was a significant increase of serum total sialic acid (TSA) and LBSA, together with significant decreases of serum Se and vitamin E concentrations (p < 0.001). One month after treatment, a reversal of trend was observed with decreases of TSA and LBSA and increases of Se and vitamin E concentrations. The TSA and LBSA levels, however, remained significantly higher than those of the controls, p < 0.05 and 0.001, respectively. The Se and vitamin E concentrations of the treated animals were the same as those of controls. This is the first study on total and LBSA concentrations in lambs with WMD, showing that these markers can be used in the prognosis of the disease.     

Proteomic comparison of human and great ape blood plasma reveals conserved glycosylation and differences in thyroid hormone metabolism

Most blood plasma proteins are glycosylated. These glycoproteins typically carry sialic acid-bearing sugar chains, which can modify the observed molecular weights and isoelectric points of those proteins during electrophoretic analyses. To explore changes in protein expression and glycosylation that occurred during great ape and human evolution, we subjected multiple blood plasma samples from all these species to high-resolution proteomic analysis. We found very few species-specific differences, indicating a remarkable degree of conservation of plasma protein expression and glycosylation during approximately 12 million years of evolution. A few lineage-specific differences in protein migration were noted among the great apes. The only obvious differences between humans and all great apes were an apparent decrease in transthyretin (prealbumin) and a change in haptoglobin isoforms (the latter was predictable from prior genetic studies). Quantitative studies of transthyretin in samples of blood plasma (synthesized primarily by the liver) and of cerebrospinal fluid (synthesized locally by the choroid plexus of the brain) confirmed approximately 2-fold higher levels in chimpanzees compared to humans. Since transthyretin binds thyroid hormones, we next compared plasma thyroid hormone parameters between humans and chimpanzees. The results indicate significant differences in the status of thyroid hormone metabolism, which represent the first known endocrine difference between these species. Notably, thyroid hormones are known to play major roles in the development, differentiation, and metabolism of many organs and tissues, including the brain and the cranium. Also, transthyretin is known to be the major carrier of thyroid hormone in the cerebrospinal fluid, likely regulating delivery of this hormone to the brain. A potential secondary difference in retinoid (vitamin A) metabolism is also noted. The implications of these findings for explaining unique features of human evolution are discussed.     

Inhibition of telomerase activity and human telomerase reverse transcriptase gene expression by histone deacetylase inhibitor in human brain cancer cells

The aim of the present study is to investigate the effect of histone deacetylase inhibitor, trichostatin A (TSA) on the cell growth, apoptosis, genomic DNA damage and the expression of telomerase and associated factors in human normal and brain cancer cells. Here, human normal un-transformed fibroblasts (MRC-5), human normal hTERT-immortalised fibroblasts (hTERT-BJ1) and human brain cancer cell lines (glioblastoma cell line, A-172 and medulloblastoma cell line, ONS-76) were treated with 0.5–3.0 μM TSA for 24 h. Exposure to TSA resulted in apoptosis in a dose-dependent manner in the brain cancer cells. Glioblastoma cell line (A-172) displayed higher sensitivity to TSA-induced cell killing effect and apoptosis than the medulloblastoma cell line (ONS-76). The brain cancer cell lines and hTERT-BJ1 cell line displayed significant inhibition in telomerase activity and hTERT mRNA level after 2 μM TSA treatment. Elevated expressions of p53 and p21 with a decrease in cyclin-D level supported the observation on cell cycle arrest following TSA treatment. Upregulation of Bax and cytochrome c correlated with the apoptotic events in TSA-treated cells. This study suggests that telomerase and hTERT might be the primary targets of TSA which may have the potential to be used as a telomerase inhibitor in cancer therapy.     

Growth factor-receptor pathway interfering treatment by somatostatin analogs and suramin: Preclinical and clinical studies

Interference in growth factor mediated pathways is a new strategy in the treatment of cancer. Somatostatin analogs can inhibit hormone and growth factor secretion, while suramin can block the binding of several growth factors to their receptors. In addition, somatostatin analogs can cause direct growth inhibitory effects after binding to tumoral somatostatin receptors. We tested the efficacy and endocrine effects of chronic treatment with three somatostatin analogs (Sandostatin,^® RC-160 and CGP 15–425) or suramin in several tumor models and in patients with various types of cancer. Treatment with somatostatin analogs caused growth inhibition of breast cancer cells (MCF-7) in vitro, and of rat transplantable pancreatic (50–70% inhibition) and prostatic Dunning tumors (12% inhibition). No tumor growth inhibition was observed with respect to DMBA-induced rat mammary tumors, a transplantable color tumor and a rhabdomyosarcoma in rats. In 34 patients with metastatic pancreatic or gastrointestinal adenocarcinomas chronic Sandostatin treatment caused stable disease in 27% of the patients, but no objective remissions. Somatostatin receptors were found in the responding MCF-7 mammary tumor cells, rat pancreatic tumors and in 20–45% of human breast cancer specimens [J. Steroid Biochem. Molec. Biol. 37 (1990) 1073–1077], but not in rat DMBA-mammary tumors or in 10 human pancreatic adenocarcinomas. Suramin caused significant dose-dependent growth inhibition of human breast cancer cells in vitro and of rat pancreatic tumors in vivo in the presence of plasma levels up to 150 μg/ml. In a preliminary clinical study concerning 11 patients with various tumor types we observed significant hematological, biochemical, endocrine and clinical side effects, but no objective remissions in spite of relevant peak plasma suramin concentrations of 270–330 μg/ml. In conclusion: somatostatin analogs and suramin can cause growth inhibition of various experimental tumors in vitro and in vivo, but the clinical values has to be established for several types of cancer, especially with respect to suramin and suramin-like compounds.     

Visualization of Sialidase Activity in Mammalian Tissues and Cancer Detection with a Novel Fluorescent Sialidase Substrate

Sialidase removes sialic acid from sialoglycoconjugates and plays crucial roles in many physiological and pathological processes. Various human cancers express an abnormally high level of the plasma membrane-associated sialidase isoform.Visualization of sialidase activity in living mammalian tissues would be useful not only for understanding sialidase functions but also for cancer diagnosis. However, since enzyme activity of mammalian sialidase is remarkably weak compared with that of bacterial and viral sialidases, it has been difficult to detect sialidase activity in mammalian tissues. We synthesized a novel benzothiazolylphenol-based sialic acid derivative (BTP-Neu5Ac) as a fluorescent sialidase substrate. BTP-Neu5Ac can visualize sialidase activities sensitively and selectively in acute rat brain slices. Cancer cells implanted orthotopically in mouse colons and human colon cancers (stages T3-T4) were also clearly detected with BTP-Neu5Ac. The results suggest that BTP-Neu5Ac is useful for histochemical imaging of sialidase activities.     

Serum sialylation changes in cancer

Cancer is a major cause of death in both developing and developed countries. Early detection and efficient therapy can greatly enhance survival. Aberrant glycosylation has been recognized to be one of the hallmarks of cancer as glycans participate in many cancer-associated events. Cancer-associated glycosylation changes often involve sialic acids which play important roles in cell-cell interaction, recognition and immunological response. This review aims at giving a comprehensive overview of the literature on changes of sialylation in serum of cancer patients. Furthermore, the methods available to measure serum and plasma sialic acids as well as possible underlying biochemical mechanisms involved in the serum sialylation changes are surveyed. In general, total serum sialylation levels appear to be increased with various malignancies and show a potential for clinical applications, especially for disease monitoring and prognosis. In addition to overall sialic acid levels and the amount of sialic acid per total protein, glycoprofiling of specific cancer-associated glycoproteins, acute phase proteins and immunoglobulins in serum as well as the measurements of sialylation-related enzymes such as sialidases and sialyltransferases have been reported for early detection of cancer, assessing cancer progression and improving prognosis of cancer patients. Moreover, sialic-acid containing glycan antigens such as CA19–9, sialyl Lewis X and sialyl Tn on serum proteins have also displayed their value in cancer diagnosis and management whereby increased levels of these factors positively correlated with metastasis or poor prognosis.     

Expression of Gangliosides GD3 and 3'-isoLM1 in Autopsy Brains from Patients with Malignant Tumors

Abstract: Three autopsy brains from patients who succumbed to malignant gliomas have been analyzed in various regions with regard to their ganglioside content. The study focused on the gangliosides GD3 and 3'-isoLM1, which in a previous study of biopsies were found to be associated with these tumors. In particular, 3'-isoLM1, was suggested to be a marker for malignant gliomas. The highest concentrations (200–1,000 nmol of sialic acid/g wet weight) of GD3 was found in specimens of macroscopically pure tumor, where the proportion of GD3 was, at the most, 78% (range, 11–78%) of the total ganglioside sialic acid compared with <10% in normal brain tissue. The proportion of the total ganglioside sialic acid made up by GD3 was also elevated in the periphery of the tumor and in the same region in the opposite hemisphere, where no tumor cells were detected. In four of eight brain metastases of various carcinomas, GD3 was >10% of the total ganglioside sialic acid (range, 3–37%). The ganglioside 3'-isoLM1, as determined by TLC-enzyme-linked immunosorbent assay using a specific monoclonal antibody (SL-50), was not present at detectable levels in any of the macroscopically homogenous tumor areas. It was, however, found in the periphery of the tumor, in the corpus callosum, and at highest concentrations in the region of the opposite hemisphere corresponding to the tumor. The concentration varied between 0.1 and 6.0 nmol/g wet weight of tissue. The 3'-isoLM1 ganglioside was not detected in normal gray or white matter or in the normal corpus callosum, but in one of three breast cancer metastasis, one of two low differentiated cancer metastases, and one stomach cancer. The concentration was 1–4 nmol/g wet weight. These results indicate a unique distribution of the gangliosides GD3 and 3'-isoLM1 and suggest that they play distinct roles in interaction between tumor cells and brain.     

Selenoenzymes,Laboratory Parameters,and Trace Elements in Different Types of Thyroid Tumor

This study was performed to investigate selenoenzyme activities and trace element concentrations in thyroid tissues, with reference to other parameters routinely used to characterize thyroid function. This was to reveal relevant parameters as possible additional markers of tumor grade, clinical course, and prognosis of thyroid disorders. The tissue samples were obtained during surgical treatment (total or near total thyroidectomy) of 122 patients with different types of thyroid tumor. For most of the investigated parameters in different groups of patients, we did not find statistically significant differences. In the majority of cases, thyroid benign or malignant tumors were not accompanied by significant derangement of the gland selenoenzymes and of either intrathyroidal or plasma concentration of selenium. Nevertheless, types I and II iodothyronine deiodinases were the most promising (among selenoenzymes) targets for diagnoses and possibly therapy of thyroid tumors. Higher activities of both enzymes in cases with Graves’ disease, as compared with other thyroid lesions, suggest their involvement in the pathogenesis of this condition. Patients with struna nodosa had higher levels of thyroid Zn, Cu, and Pb as compared with papillary carcinoma subjects and also a higher level of Cu than follicular carcinoma cases. The above diagnostics may play a similar role to some of the general thyroid function indices, TSH, anti-TG, anti-TPO, and calcitonin, which can partially distinguish between various thyroid tumors. In conclusion, some of selenium status markers, when accompanied with general parameters, and trace elements can serve as factors with pathophysiologic relevance and be helpful in the identification of malignant disease. Multivariate statistical methods should be employed to tackle a broad array of thyroid tumor diagnostic data in a short time. Partial least squares model and other pattern recognition methods seem to be the most appropriate methods for that task. The miniaturization of all the steps of complex analytical procedure should be developed in a way to allow its completion as sensitive, robust, and efficient for use of the small quantity of material provided by fine-needle biopsy.     

Gangliosides in human, cow and goat milk, and their abilities as to neutralization of cholera toxin and botulinum type A neurotoxin

To elucidate the potential of mammalian milk as to protection of infants from infections, we determined the ganglioside compositions of human, cow and goat milk in relation with cholera toxin and botulinum type A neurotoxin-receptors. Gangliosides accounted for 1 to 2 μmol of lipid-bound sialic acid (LSA) in 100 ml of milk, and GD3 comprised about 69% of LSA in all milk samples. Among the milk samples examined, goat milk was found to contain an amount of gangliosides belonging to the b-pathway representing 15.8% of the total LSA. Accordingly, botulinum neurotoxin bound to GT1b and GQ1b in goat milk, but not to any gangliosides in human or cow milk. On the other hand, GM1, the cholera toxin receptor, was found to be present in all milk samples at concentrations of 0.02% to 0.77% of the total LSA and to be maintained at a relatively constant level in human milk during the postpartum period. Gangliosides from 1 ml of pooled human milk exhibited the ability to attenuate the binding of cholera toxin (30 ng) to GM1 by 93%, and those from 500 μl of goat milk completely inhibited the binding of botulinum type A neurotoxin 1.5 μg to GT1b. The glycolipid nomenclature is based on the recommendations of the IUPAC-IUB Commission on Biochemical Nomenclature [1]. The ganglioside nomenclature of Svennerholm is employed throughout [2]. PVP, polyvinylpyrrolidone; LSA, lipid-bound sialic acid.