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B Rigas

Publications and source records attributed to B Rigas.

At least 73 records · Page 4Linked to original sources

Human colon adenocarcinoma cell lines display infrared spectroscopic features of malignant colon tissues.

Seven human colon cell lines were studied by infrared spectroscopy including study of several spectral parameters under high pressure (pressure tuning spectroscopy). The results were compared to those obtained from the study of normal and malignant colon tissues (B. Rigas et al., Proc. Natl. Acad. Sci. USA, 87: 8140-8144, 1990; P. T. T. Wong and B. Rigas., Appl. Spectrosc., 44: 1715, 1990). The seven adenocarcinoma cell lines displayed almost all of the important spectroscopic features of colon cancer tissues: (a) increased hydrogen-bonding of the phosphodiester groups of nucleic acids; (b) decreased hydrogen-bonding of the C--OH groups of carbohydrates and proteins; (c) a prominent band at 972 cm-1; and (d) a shift of the band normally appearing at 1082 cm-1 to 1086 cm-1. These cell lines differed spectroscopically from the colon cancer tissues in that: (a) they displayed a band at 991 cm-1, which is weak in colon tissues; and (b) the packing and degree of disorder of membrane lipids were close to those observed in normal colonic tissues. These findings (i) establish IR spectroscopy, used in combination with pressure tuning, as a useful method to address problems of tumor biology in cell culture systems, (ii) indicate that these cell lines offer a useful experimental model to explore the origin of the spectroscopic changes that we observed in colon cancer tissues, and (iii) support the idea that the malignant colonocyte is the likely source of all or most spectroscopic abnormalities of human colon cancer.

Adenocarcinoma↗

Infrared spectroscopy of exfoliated human cervical cells: evidence of extensive structural changes during carcinogenesis.

Infrared spectra were obtained from exfoliated cervical cells from 156 females, of whom 136 were normal, 12 had cervical cancer, and 8 had dysplasia. The spectra of the normal women, essentially identical, differed from those obtained from patients with either cancer or dysplasia. In malignant samples we noted (i) significant changes in the intensity of the glycogen bands at 1025 cm-1 and 1047 cm-1, the bands at 1082 cm-1 and 1244 cm-1, the C--O stretching band at 1155 cm-1, and the band at 1303 cm-1, (ii) significant shifts of the peaks normally appearing at 1082 cm-1, 1155 cm-1, and 1244 cm-1, and (iii) an additional band at 970 cm-1. Further study of several of these bands, including the pressure dependence of their frequencies, revealed that in the malignant cervical tissue there were extensive changes in the degree of hydrogen bonding of phosphodiester groups of nucleic acids and C--OH groups of proteins, as well as changes in the degree of disorder of methylene chains of lipids. The IR spectra of samples with dysplasia demonstrated the same changes with cancer samples, except that the changes were of lesser magnitude and the phosphodiester peak normally appearing at 1082 cm-1 did not shift. These spectroscopic changes appear to progress in tandem with the morphological changes that lead normal cervical epithelium to cancer through the premalignant stage of dysplasia. The diagnostic potential of IR spectroscopy is discussed.

Cervix Uteri↗

Circadian periodicity and other clinical features of biliary pain.

We studied the time of onset and other clinical features of biliary pain in 54 patients living in Northern Italy. All patients had cholelithiasis documented by ultrasonography. The time of onset of pain followed a circadian periodicity with its peak occurring at 9:30 p.m. The typical biliary pain was steady, mostly localized in the right upper quadrant of the abdomen or the epigastrium, lasted over 1 h, and required analgesics for relief. The pain was not related to meals or body position. What precipitates biliary pain is still an enigma.

Cholelithiasis↗

Reduced expression of HLA class I and II antigens in colon cancer.

The expression of HLA class I and II antigens was studied by immunohistochemistry in (a) specimens of colon cancer from 25 patients, (b) normal colonic mucosa obtained 5-10 cm away from each tumor, and (c) colonic mucosa from 13 normal individuals. Thirteen of the tumor specimens had normal epithelium adjacent to the cancer, which thus served as an internal control. The expression of HLA class I antigens in colon cancer was dramatically reduced compared to control (P less than 0.0001): undetectable in 28%, diminished in 68%, normal in 4%. The expression of class II antigens was also reduced in cancer (P less than 0.0001 for all when compared to normal), being undetectable in most (HLA-DP 64%, HLA-DQ 72%, HLA-DR 68%). In 44% of the cancers all three HLA class II antigens were undetectable; in 92% at least one class II antigen was undetectable; and in 20% both class I and class II antigens were undetectable. No cancer specimen had a completely normal HLA phenotype. The expression of other surface antigens was preserved in cancer tissues and, therefore, loss of HLA antigens was not due to a nonspecific decline in surface molecules. When glands of normal mucosa immediately adjacent to cancer were compared to those of normal controls, significantly reduced expression of only HLA class I antigens (P = 0.0149) and HLA-DP (P = 0.034) was found. The expression of the HLA antigens in colonic mucosa remote from the cancer was no different from that of normal controls. Our data show extensive and significant reduction in the expression of HLA antigens in colon cancer; its potential relationship to immunosurveillance in cancer is discussed.

Colon↗

TGF-alpha and TGF-beta expression during sodium-N-butyrate-induced differentiation of human keratinocytes: evidence for subpopulation-specific up-regulation of TGF-beta mRNA in suprabasal cells.

Sodium-N-butyrate (NaB) induces terminal differentiation and cornified envelope formation in cultured human keratinocytes. In the present study we explored the question of whether NaB-induced maturation could be mediated through changes in TGF-alpha and TGF-beta expression in normal keratinocytes. NaB induced a four-fold increase in TGF-beta mRNA transcript levels. This increase in TGF-beta mRNA abundance occurred only within the nonbasal keratinocyte subpopulation which maximally responds to NaB treatment by progression to cornified envelopes. Basal keratinocytes, which are relatively refractive to cornified envelope formation, did not show any increase in TGF-beta mRNA abundance after NaB treatment. By comparison, TGF-alpha mRNA transcript and extracellular TGF-alpha protein levels were unaffected by NaB treatment. A 50% decrease in EGF receptor binding was observed in NaB-treated keratinocyte cultures, rendering the cells less responsive to proliferation induction.

Butyrates↗

Human colorectal cancers display abnormal Fourier-transform infrared spectra.

Fourier-transform infrared spectroscopy (FT-IR) was applied to the study of tissue sections of human colorectal cancer. Pairs of tissue samples from colorectal cancer and histologically normal mucosa 5-10 cm away from the tumor were obtained from 11 patients who underwent partial colectomy. All cancer specimens displayed abnormal spectra compared with the corresponding normal tissues. These changes involved the phosphate and C-O stretching bands, the CH stretch region, and the pressure dependence of the CH2 bending and C = O stretching modes. Our findings indicate that in colonic malignant tissue, there are changes in the degree of hydrogen-bonding of (i) oxygen atoms of the backbone of nucleic acids (increased); (ii) OH groups of serine, tyrosine, and threonine residues (any or all of them) of cell proteins (decreased); and (iii) the C = O groups of the acyl chains of membrane lipids (increased). In addition, they indicate changes in the structure of proteins and membrane lipids (as judged by the changes in their ratio of methyl to methylene groups) and in the packing and the conformational structure of the methylene chains of membrane lipids. The cell(s) of the malignant colon tissues responsible for these spectral abnormalities is unknown. Cultured colon adenocarcinoma cell lines displayed similarly abnormal FT-IR spectra. The diagnostic potential of the observed changes is discussed.

Adenocarcinoma↗

The circadian rhythm of biliary colic.

We evaluated 50 consecutive patients with symptomatic gallstones for the clinical features of biliary pain with particular reference to the timing of their painful episodes. Thirty-eight of the 50 patients were able to provide the time of onset of biliary pain in the 24-h cycle. The time of onset of biliary pain displays significant circadian periodicity (p = 0.0032), with its peak at 00:25 h. Forty-five patients had more than 1 episode of pain. Of these 84% had either all or over half of their attacks of biliary pain at the same clock time. Twenty-two patients with renal colic (a close parallel to biliary pain) and 31 patients with episodic abdominal pain from miscellaneous causes showed no circadian or other periodicity in the time of onset of pain. In only 1 of these patients did the abdominal pain recur consistently at the same clock time. "Typical" biliary pain has its onset at night and tends to recur at the same clock time. It is steady and relatively mild, lasting 1-5 h, it is felt in the right upper quadrant or the epigastrium, may radiate to a variety of sites, is associated with some additional symptoms, and is not usually related to meals. The chronobiological and other features of biliary pain reported here should be useful in the diagnostic evaluation of abdominal pain.

Adolescent↗

Circadian periodicity of the time of onset of acute lower gastrointestinal bleeding.

We investigated the chronobiological parameters of acute gastrointestinal (GI) bleeding in 51 patients able to time-specify the onset of bleeding within 30 min of occurrence. Bleeding was determined to be either from the upper or lower GI tract. The upper GI bleeding group consisted of 32 patients (22 male, 10 female) who bled from peptic ulcer disease (16), Mallory-Weiss tear (4), gastritis (3), esophageal varices (3), gastric neoplasm (2), Dieulafoy's lesion (1), and unknown (3). The lower GI bleeding group consisted of 19 patients (9 male, 10 female) who bled from diverticulosis coli (5), hemorrhoids (2), arteriovenous malformations (2), colonic polyps (2), cecal ulcer (1), antibiotic-associated colitis (1), and unknown (6). Rhythmicity was evaluated by inferential statistics. The time of onset of lower GI bleeding (34 episodes) displayed significant circadian periodicity (p = 0.014) with its peak at 1100 h. Single cosinor analysis revealed: MESOR-1.42 (95% CI = 0.86- 1.97); amplitude = 1.22 (0.44-1.99); phase angle = -165.12 (-201.66 -128.58). Upper GI bleeding (42 episodes) displayed no circadian periodicity (p = 0.46). When both upper and lower GI bleeding were evaluated together, no circadian rhythm was evident (p = 0.07). We conclude that there is a circadian periodicity in the time of onset of only acute lower GI bleeding with its peak at 1100 h. The pacemaker of this periodicity remains unknown.

Acute Disease↗

Oncogenes and suppressor genes: their involvement in colon cancer.

Abnormalities in oncogenes, which are broadly classified into viral and cellular oncogenes, and suppressor genes appear critical for the development of colon cancer. Cellular oncogenes contribute to malignant transformation when they become activated by point mutation, translocation, amplification, or loss of regulator sequences. The properties of the oncoproteins, the proteins encoded by oncogenes which are essential for carcinogenesis, are unclear. Suppressor genes normally suppress the tumorigenic phenotype by keeping the growth of cells in check; it is their inactivation that contributes to malignant transformation. Development of colon cancer appears to take place by stepwise accumulation of multiple genetic alterations during the progression from normal colon to adenoma and carcinoma. Activation of ras, an early event in this sequence, is found in 50% of colon cancers; overexpression of c-myc is found in approximately 80%. Inactivation of suppressor genes, which occurs during later stages, is noted in greater than 70% of tumors. A current model of colonic tumorigenesis is presented.

Colonic Neoplasms↗

Prostaglandins E2 and E2 alpha are elevated in saliva of cystic fibrosis patients.

Several products of arachidonic acid metabolism were assayed in whole saliva of patients with cystic fibrosis, a disease affecting primarily the exocrine glands. The levels of prostaglandins (PG) E2 and F2 alpha were elevated fourfold in patients with cystic fibrosis, compared with a control group (mean +/- SEM for PGE2 1.13 +/- 0.22 vs 0.37 +/- 0.08 ng/ml saliva, p less than 0.005; and for PGE2 alpha 0.84 +/- 0.27 vs 0.17 +/- 0.03 ng/ml saliva, p less than 0.025). The levels of PGI2, hydroxyeicosatetraenoic acids, and leukotrienes showed no significant differences between the two groups. These changes were not present in individuals heterozygous for the cystic fibrosis gene. Study of appropriate control groups suggested that the changes that we observed in patients with cystic fibrosis could not be attributed to their lung disease or to the medications these patients were receiving. Our findings indicate that metabolism of arachidonic acid is abnormal in cystic fibrosis.

Adolescent↗

Rapid plasmid library screening using RecA-coated biotinylated probes.

A method for the rapid physical isolation of recombinant plasmids of interest from a mixture of plasmids such as a plasmid cDNA library is presented. This method utilizes the ability of RecA protein to form stable complexes between linear single-stranded and circular double-stranded DNA molecules sharing sequence homology, and procedures allowing isolation of biotinylated nucleic acid. Biotinylated linear DNA probes coated with RecA have been used to screen reconstituted plasmid libraries consisting of two plasmid species, one homologous and the other heterologous to the probe. When the link between biotin and the nucleotide base could be cleaved by reducing agents, the complex was purified by streptavidin-agarose chromatography and the recovered plasmid was propagated in Escherichia coli. When the link was not cleavable the complex was bound to avidin in solution and purified by cupric iminodiacetic acid-agarose chromatography. The complex was then dissociated and the plasmids were propagated in E. coli. With either protocol, homologous plasmid recovery was between 10% and 20%, and enrichment was between 10(4)- and 10(5)-fold. Potential applications and extensions of this method, such as plasmid, cosmid, and phage library screening and facilitation of physical mapping of macroregions of mammalian genomes are presented and discussed.

Adenosine Triphosphate↗

Amiodarone hepatotoxicity. A clinicopathologic study of five patients.

Five patients had amiodarone hepatotoxicity detected on routine biochemical monitoring. Symptoms attributable to hepatotoxicity were minimal or absent; reversible hepatomegaly was seen in two patients, whereas three patients had signs of nonhepatic amiodarone toxicity before or with hepatotoxicity. Serum aminotransferase levels were elevated in all patients and alkaline phosphatase levels in four; no patient had hyperbilirubinemia or prolongation of the prothrombin time. Light microscopy showed steatosis, cellular degeneration, and cellular necrosis in the biopsy samples of four patients, whereas the fifth patient's sample had a granulomatous injury pattern. Electron microscopic study of liver tissue done in two patients showed phospholipid-laden lysosomal lamellar bodies. These findings suggest that both toxic and hypersensitivity liver injury can occur in response to amiodarone. The presence of phospholipid-laden lysosomal lamellar bodies may help differentiate amiodarone hepatotoxicity from alcoholic liver disease or other causes of hepatic steatosis.

Aged↗

Human salivary eicosanoids: circadian variation.

A circadian rhythm in the concentrations of prostaglandins (PG) E2, PGF2, PGI2 (measured as 6-keto-PGF1 alpha), immunoreactive h hydroxyeicosatetraenoic acids and immunoreactive 6-sulfidopeptide containing leukotrienes in human mixed saliva was observed. The rhythm reflected changes in the absolute amounts of these compounds in saliva. Under usual sleep-wake cycles a single peak occurred during sleep with maximal levels at 5:00 AM; the amplitude of the peak varied for each product. The rhythm was sleep-dependent and a shift occurred when the sleep-wake cycles were displaced. Basal levels of these eicosanoids were maintained even without sleep.

Adult↗

Identification and quantitation of arachidonic-acid metabolic products in rabbit, rat and human saliva.

Arachidonic-acid metabolites were identified in salivary secretions of rabbits, rats and man and in homogenates of rabbit parotid and submandibular glands. The following levels were determined in mixed saliva of healthy volunteers: PGE2, 0.65 +/- 0.8 ng/ml; PGF2 alpha, 0.41 +/- 0.06 ng/ml; serologically active hydroxyeicosatetraenoic acids (HETE) 319.6 +/- 36.6 ng/ml; serologically active 6-sulphidopeptide-containing leukotrienes 1.72 +/- 0.21 ng/ml (all values mean +/- SEM). In all instances, HETE markedly predominated over all other arachidonic-acid metabolites.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

Concentrations of arachidonic-acid metabolites in human mixed saliva are independent of flow rate.

Three prostaglandins, PGE2, PGF2 alpha and PGI2 (measured as 6-keto-PGF1 alpha), serologically active 6-sulphidopeptide-containing leukotrienes and hydroxyeicosatetraenoic acids were determined by radioimmunoassay of mixed saliva obtained at several flow rates from 8 healthy volunteers. Flow rates ranged from 0.26 +/- 0.02 ml/min when saliva production was unstimulated to 1.18 +/- 0.14 ml/min (values mean +/- SEM) when maximally stimulated. Concentrations of all compounds tested remained independent of changes in mixed-saliva flow rate.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗