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Biomedical subjects

S Mobarhan

Publications and source records attributed to S Mobarhan.

At least 37 records · Page 2Linked to original sources
PubMed1995

Effect of beta-carotene supplementation on indices of colonic cell proliferation.

BACKGROUND: Epidemiologic studies have shown that consuming foods containing beta-carotene is associated with a decreased incidence of colon cancer. The validity of this association has recently been questioned. It is not known if the rate of colonic cell proliferation differs among individuals with or without a history of colonic polyps or cancer and if proliferation changes in response to beta-carotene. PURPOSE: This study was intended to (a) determine whether differences exist in colonic cell proliferation in individuals with and without prior colonic polyps or tumors, (b) demonstrate that beta-carotene accumulates in colonic mucosa following dietary supplementation, and (c) determine whether mucosal beta-carotene accumulation influences colonic cell proliferation. METHODS: Subjects were enrolled in the phase I study from June 1991 until February 1994. The participants included 20 individuals (11 males and nine females, aged 62.3 +/- 8.9 years [means +/- SD]) with normal colons (as judged by recent colonoscopy), 40 (24 males and 16 females, aged 59.6 +/- 10.1 years) with a history of colonic polyp(s), and 41 (30 males and 11 females, aged 67.2 +/- 9.7 years) with prior colon cancer. The subjects in the last two groups consumed either 30 mg of beta-carotene or placebo each morning for 3 months. This dose of beta-carotene has no known toxic effects, but it can increase the serum level by approximately 10-fold. beta-carotene concentration in serum and colonic tissue was quantitated by high-pressure liquid chromatography in samples collected before and after supplementation with beta-carotene or placebo. Cellular proliferation was assessed on the basis of tissue ornithine decarboxylase activity, urinary polyamine excretion, and proliferating cell nuclear antigen expression. The differences in colonic cell proliferation parameters due to beta-carotene supplementation, within and among different groups, were evaluated by the Wilcoxon matched-pairs signed ranked test and the Mann-Whitney test, respectively. All statistical tests were two-sided. RESULTS: Colonic cell proliferation did not differ in samples obtained from individuals with and without prior colonic polyp(s) or cancer. beta-carotene concentrations in serum and colonic tissue were significantly increased in groups receiving beta-carotene (P < .001). However, cell proliferation did not differ, as judged by any of the three measures, among samples from all experimental groups collected before and after supplementation with beta-carotene. CONCLUSIONS: Dietary supplementation with beta-carotene for a period of 3 months does not alter colonic cell proliferation in individuals with a history of colonic polyps or cancer. IMPLICATIONS: The mechanism by which beta-carotene might reduce colon cancer incidence does not appear to involve or result in a change in cell proliferation in the normal colonic mucosa as studied in individuals with a history of colonic polyps or cancer.

Adult↗
PubMed1995

Urinary organ specific neoantigen. A potentially diagnostic test for colorectal cancer.

Urinary organ-specific neoantigen from colorectal cancer patients has been used to make a monoclonal antibody, BAC 18.1. In this study we assessed the potential of this antibody for the diagnosis of colorectal cancer. We evaluated binding in both urine and effluent samples and compared it with effluent carcinoembryonic antigen standardized for both volume (nanograms per milliliter) and protein. Urinary organ-specific antigen as detected by BAC 18.1 was significantly greater in 29 cancer patients (A405: 0.717 +/- 0.500) vs 27 controls [0.121 +/- 0.273 (P < 0.05)]. Considerable overlap of binding of BAC 18.1 was observed in the colonic effluent of patients with CRC (N = 13), adenomas (N = 26), inflammatory bowel disease (N = 8), or having a normal colonoscopic examination (N = 24). CEA levels (nanograms per milliliter) were significantly elevated in the effluent samples of patients with a past history of colorectal cancer, as compared to that of normal individuals (P < 0.05). The presence of the M(r) 30,000 organ-specific neoantigen in colonic effluent was also demonstrated by western blot. Organ-specific neoantigen originates in the colon and is excreted into the urine, so the BAC 18.1 binding levels in the urine may be a diagnostic aid for CRC.

Adult↗
PubMed1995

Serum retinoic acid levels in patients with resected benign and malignant colonic neoplasias on beta-carotene supplementation.

To determine whether patients with colon cancer metabolize beta-carotene differently from benign colon polyp patients, a normal control group (n = 13) and groups of resected colon polyp patients (n = 29) or resected colon cancer patients (Dukes A and B1, n = 21) were supplemented with placebo or beta-carotene (30 mg/day) taken with their morning meals for three months. Serum samples at zero and three months of the study were analyzed blindly for retinoic acid and beta-carotene. The results showed that beta-carotene levels in the serum of colon polyp and colon cancer groups were 8- to 12-fold higher than in the untreated control or the placebo-treated groups. The benign polyp subjects (n = 17) receiving beta-carotene showed a significant rise in serum trans-retinoic acid at three months compared with Time 0. The trans-retinoic acid values from the colon cancer group receiving beta-carotene (n = 11) or placebo (n = 10) were significantly lower than the values from the beta-carotene-supplemented colon polyp group. It appears that trans-retinoic acid levels in response to beta-carotene supplementation are different between treated cancer and benign patients because of different body demands for retinoic acid.

Adult↗
PubMed1995

Accumulation of beta-carotene in normal colorectal mucosa and colonic neoplastic lesions in humans.

The quantity of beta-carotene (BC) accumulated in colonic polyps and colonic cancerous tissue in humans in situ was determined relative to the quantity accumulated in normal colon and rectal tissue. Serum concentration of BC, retinol, and alpha-tocopherol and tissue BC concentration were determined by high-performance liquid chromatography in samples obtained before and after oral supplementation with BC (30 mg/day). The serum BC and retinol concentrations significantly increased in response to supplementation in control, polyp, and cancer patients, but there was no change in serum alpha-tocopherol concentration. The BC concentration in tissue (colon, rectum, and tumor) of cancer patients was significantly less than that in tissue samples from control and polyp patients. Relative to baseline values, BC accumulated to a significant extent in tissues from all patients, including polyp and tumor tissue, during supplementation. The results indicate that BC does accumulate in colonic neoplastic tissue in humans and may potentially be utilized to augment cytotoxicity of chemotherapeutics or to prevent malignant transformation of cells.

Adenomatous Polyps↗
PubMed1995

Evidence from cancer intervention and biomarker studies and the development of biochemical markers.

Evidence from intervention trials with vitamins E and C and beta-carotene are reviewed as well as evidence from trials that have used intermediate endpoints with a special emphasis on biomarkers of cancer of the colorectum. The methodologic issues that require resolution before a second generation of clinical trials are launched to assess the efficacy of these antioxidants in the prevention of cancer are identified. Specific concerns regarding the validation of pathologic biomarkers of cancer and biochemical markers of mechanism of action for the antioxidants are discussed. Cellular proliferation indexes in the colon are used as an example of pathologic biomarkers for cancer and the measurement of plasma and tissue malondialdehyde concentrations is used as an example of problems with the development of biochemical markers of oxidative stress that can be used in prevention trials. The use of DNA oxidation products as promising biomarkers is also discussed.

Antioxidants↗
PubMed1995

Diarrhea induced by enteral feeding.

Diarrhea is reported as a major complication of enteral feeding. Recent studies show that there is a staggering amount of confusion in defining diarrhea in this setting. This causes major problems both in estimating the incidence of diarrhea, as well as determining its clinical impact. In many cases, careful review of the patients' records and evaluation of the diarrhea may lead to its accurate diagnosis and treatment. The frustration involved in the management of these patients may lead investigators to measure quantitatively the patient's fecal output and to come up with a standardized definition of diarrhea. We describe here three cases that show various forms of enteral feeding-induced diarrhea. Subsequently we will review the important issues regarding the definition of related diarrhea and attempt to understand its pathogenesis.

Adolescent↗
PubMed1995

Mucosal reactive oxygen species production in oesophagitis and Barrett's oesophagus.

Reactive oxygen species (ROS) produced by inflammatory cells can contribute to tissue destruction. ROS have been implicated in various gastrointestinal abnormalities, including the acid related peptic diseases. Although the development of oesophagitis and Barrett's columnar epithelium is associated with prolonged reflux of gastric acid, the exact mechanism by which tissue damage occurs is not known. To discover if ROS are involved in damage to the oesophageal mucosa, this study measured in vitro the mucosal ROS concentrations of biopsied mucosal samples taken from patients with reflux oesophagitis using luminol enhanced chemiluminescence (LECL). Mucosal biopsy specimens were taken from 83 patients: 19 with normal oesophageal mucosa (group I); 20 with macroscopic oesophagitis (group II); 20 with biopsy confirmed Barrett's epithelium without macroscopic oesophagitis (group III); and 24 with Barrett's epithelium with macroscopic oesophagitis (group IV). The mucosa from patients exhibited significantly higher LECL values than the mucosa from controls. But, there were no significant differences between groups II, III, and IV. Addition of the myeloperoxidase inhibitor, azide, or the hydrogen peroxide scavenger, catalase, to the tissue suspension caused a decrease in LECL values of 32% and 45%, respectively, suggesting that neutrophils--although important--are not the only source of mucosal LECL. These data are consistent with the proposal that ROS play an important part in the tissue injury associated with oesophagitis and Barrett's columnar epithelium.

Aged↗
PubMed1994

Expression of mRNA for the gap-junctional protein connexin43 in human colonic tissue is variable in response to beta-carotene supplementation.

Increased expression of the gap-junctional protein connexin43 (Cx43) is reported to be increased in mouse and human dermal fibroblasts in vitro in response to beta-carotene treatment. In the present study, we determined the level of Cx43 mRNA expression in colonic mucosa from normal subjects and subjects with a prior history of colonic polyps or cancer before and after three months of administration of a placebo or beta-carotene. RNA was reverse transcribed and used in a polymerase chain reaction assay employing primers selected from the human Cx43 gene sequence. Cx43 mRNA expression was normalized on the basis of beta 2-microglobulin mRNA expression. The beta-carotene concentration in colonic mucosa, as well as serum and diet, was also determined to establish a correlation between Cx43 expression and beta-carotene concentration. In an initial analysis of samples collected from 10 subjects before supplementation, the quantity of Cx43 mRNA was variable and did not correlate with beta-carotene intake or the concentration of beta-carotene in tissue or serum. In samples collected at zero and three months from eight subjects who were controls or received a placebo, there was no correlation between Cx43 mRNA level and tissue or serum beta-carotene concentration. In samples collected from subjects before and after three months of beta-carotene supplementation, there was a significant increase in tissue and serum beta-carotene concentration in all subjects and an increase in Cx43 mRNA expression after supplementation relative to baseline in four of six samples. The high variability in Cx43 expression indicates that induction of Cx43 mRNA expression is not solely dependent on the concentration of beta-carotene in diet, serum, or tissue. However, the results from subjects supplemented with beta-carotene suggest that induced expression may occur in colonic tissue of some individuals. some individuals.

Base Sequence↗
PubMed1994

Subnormal albumin gene expression is associated with weight loss in immunodeficient/DNA-repair-impaired wasted mice.

OBJECTIVE: Mice bearing the autosomal recessive mutation wst express a disease syndrome of immunodeficiency, neurologic dysfunction, increased sensitivity to the killing effects of ionizing radiation, and dramatic weight loss that begins at 21 days of age and progresses until death at 28-32 days of age. Because of the reported association between abnormal liver status and weight loss, we designed experiments to examine expression of a variety of liver-specific genes in wst/wst mice relative to littermates (wst/.) and parental strain (BCF1) controls. METHOD: Animals were individually weighed from ages 21-28 days to determine relative weight comparisons between wst/wst mice and controls. Dot blot hybridizations were set up to quantitate the accumulation of transcripts specific for alpha-fetoprotein, albumin and other liver-specific gene products. RESULTS: These results showed a 67% reduction in albumin mRNA expression in livers derived from wst/wst mice relative to both controls. Expression of alpha-fetoprotein, as well as a variety of other liver-specific genes [secretory component (SC), metallothionein (MT-2), cytochrome P1-450 (Cyt P1-450), transferrin receptor (Tf Rec), tumor necrosis factor (TNF), and immune-associated antigen (Ia)], was unaffected. CONCLUSIONS: These results suggest a relationship between low albumin expression and wasting syndromes in mice. In addition, our data suggest that the wasted mouse may serve as a unique model for subnormal albumin expression.

Animals↗
PubMed1994

Review: microbiology of the gastrostomy tube.

This review summarizes what is presently known about microbial colonization of silicone gastrostomy feeding tubes and their deterioration. Feeding tubes are frequently colonized by fungal and bacterial organisms. Candida organisms seem to originate from the oral cavity from where they colonize the stomach and the gastrostomy tubes. It appears that many microorganisms are able to metabolize certain polymer additives, and although this is well described for polyvinyl chloride, it is not for silicone elastomers. However, clinical evidence for a role of microorganisms in the deterioration of silicone feeding tubes is very strong. The clinical significance of gastrointestinal tract seeding from gastrostomy tubes, which act as incubators, is not fully understood and deserves further study. Likewise, deterioration of feeding tubes must be investigated systematically to address the safety and economical issues it presents.

Bacteria↗
PubMed1994

Assessment of the intestinal retention of beta-carotene in humans.

OBJECTIVE: Assessment of the intestinal absorption of beta-carotene (BC) in humans as well as plasma clearance of BC has been difficult. We have used the total gut washout method (TGWM) to assess BC retention during transit through the intestine, as well as the effect that different diets and age have on BC retention. METHODS: HPLC was used to quantitate fecal and serum BC concentrations from young and elderly subjects who had undergone the TGWM to remove all intestinal contents prior to ingesting BC or placebo with or without a meal. Meals contained different combinations of calories and fat. RESULTS: In subjects receiving no meal, 83% of ingested BC was recovered in rectal effluent collected within 24 hours post-BC administration. The quantity of BC in feces of individuals receiving meals was 49-71%. There was no significant change in serum concentrations of other carotenoids or retinoids following consumption of BC with any of the different meals. Interestingly, both diet and age influenced the efficiency of BC absorption. An increase in dietary fat content resulted in an higher serum BC concentration in young subjects within 8 and at 24 hours post BC administration, whereas a higher caloric content resulted in a decrease in serum BC concentration in older subjects within 8 hours of BC administration. CONCLUSION: Results indicate that the TGWM provides an accurate means for assessing the intestinal retention of BC in humans.

Adolescent↗
PubMed1994

Carbohydrate versus fat in the dietary treatment of short-bowel syndrome.

The importance of the human colon in energy salvage has been documented again in a recent clinical study. Patients with short-bowel syndrome can be divided into two groups: those with colon and those without colon in continuity. While a high-carbohydrate, low-fat diet appears to be of nutritional benefit to the former group, dietary restrictions and reduction of fat intake are not effective in reducing intestinal energy loss in the latter group.

Colon↗
PubMed1994

Micronutrient supplementation trials and the reduction of cancer and cerebrovascular incidence and mortality.

Epidemiological evidence suggests that a diet rich in fruits and vegetables may reduce the risk of various forms of cancer, most likely contributable to their vitamin and mineral content. It is believed that the vitamins and minerals in these foods contribute to a reduced risk of cancer. The population of Linxian, China is known to have one of the highest rates of esophageal/gastric cardia cancer in the world. Recent intervention studies from this particular geographic area for the first time have indicated that vitamin and mineral supplementation, specifically beta-carotene, vitamin E, and selenium, may play a role in the reduction of cancer risk.

Adult↗
PubMed1994

beta-Carotene supplementation results in an increased serum and colonic mucosal concentration of beta-carotene and a decrease in alpha-tocopherol concentration in patients with colonic neoplasia.

The aim of this study was to evaluate the colonic mucosal beta-carotene (BC) concentration following supplementation with BC and to determine if an increase in BC concentration influences vitamin E (alpha-tocopherol) status. The concentration of BC and alpha-tocopherol was assessed in serum and colonic tissue obtained from subjects with a history of colonic polyps or resected cancer (Dukes A, B1, or B2). Serum and mucosal biopsy samples were obtained prior to and following 3 months daily p.o. supplementation with 30 mg of BC or placebo. The concentration of BC was significantly increased in serum and colonic mucosa from both polyp and cancer subjects following supplementation as compared to presupplementation values and values from subjects receiving a placebo. The concentration of alpha-tocopherol in serum from cancer subjects was significantly decreased in samples obtained at the end of 3 months of BC supplementation as compared to placebo-matched controls. In BC-supplemented polyp subjects the tissue concentration of alpha-tocopherol was also significantly decreased relative to presupplementation values. The results indicate that BC supplementation does result in a significant accumulation of BC in the colonic mucosa but that the alpha-tocopherol concentration in both serum and colonic tissue may be compromised by an increased intake of BC. The mechanism for the decrease in alpha-tocopherol in conjunction with the increase in BC will require further study in order to develop strategies which will prevent vitamin E deficiency in BC-supplemented individuals.

Adult↗
PubMed1993

Pulmonary pentane excretion increases with age in healthy subjects.

Excessive lipid peroxidation occurs in various diseases. However, even in health low levels of lipid peroxidation can be detected by measuring the pulmonary excretion of pentane. Lipid peroxidation has been postulated to be one of the causes of the ageing process. In order to test whether pentane excretion is related to age, we measured breath pentane in 47 healthy subjects (ages 21-79). We also measured serum levels of the antioxidants tocopherol, retinol, lycopene, beta carotene, ascorbate and zinc. We found that pentane excretion significantly (P < 0.05, r = 0.32) increased with age. Of the six antioxidants measured, only lycopene decreased significantly (P < 0.05, r = -0.47) with age, however, this decline did not statistically correlate with pentane excretion. The remaining five antioxidants either remained stable or increased over the age range studied. We conclude that lipid peroxidation, as assessed by pentane excretion, increases with advancing age but that this increase is independent of dietary antioxidant levels.

Adult↗
PubMed1993

Increased levels of luminol-enhanced chemiluminescence by rectal mucosa of patients with colonic neoplasia: a possible marker for colonic neoplasia.

Increased colonic cell proliferation (CCP) has been reported in patients with colonic neoplasia. Previous studies in rats suggest that increased CCP is closely related to increased reactive oxygen metabolite (ROM) production. We hypothesized that, in humans, ROM production is also involved in increased CCP. Using a chemiluminescence probe, we estimated the levels of ROMs in the rectal mucosa of 37 patients who previously had colonic neoplasia (14 with cancer and 23 with polyps) and 20 control subjects who had normal colonoscopic examination and no history of colonic neoplasia. Normal-appearing rectal mucosa of patients with colonic neoplasia contained significantly higher levels of luminol-enhanced chemiluminescence (LECL) than rectal mucosa of control subjects (p < 0.01). There was no difference in LECL levels between patients with polyps and patients with cancer. Four of 20 controls and 31 of 37 patients had LECL levels 1,000 cpm/mg protein (positive and negative predictive values of 89% and 73%, respectively). Addition of indomethacin, a specific cyclooxygenase inhibitor, to the tissue suspension significantly decreased LECL levels. These preliminary data suggest that 1) ROMs may be involved in both the rate of CCP and the process of malignant cellular transformation, 2) oxidation of arachidonic acid via the cyclooxygenase pathway significantly contributes to the production of ROMs in rectal mucosa, and 3) measurement of the levels of LECL produced by the rectal mucosa may be a sensitive marker to screen for colonic neoplasia.

Adult↗
PubMed1993

Beta-carotene decreases markers of lipid peroxidation in healthy volunteers.

We previously showed that daily intake of beta-carotene, a nontoxic antioxidant, reduces lipid peroxidation as assessed by serum lipid peroxide levels. An alternative method to detect lipid peroxidation is the measurement of pentane in breath. Pentane is a five-carbon hydrocarbon that is released when an omega-6 unsaturated fatty acid undergoes peroxidation. The aim of this study was to see whether graded doses of beta-carotene would affect breath pentane excretion in normal subjects placed on a carotenoid-free liquid diet for two weeks. The subjects were then repleted with either 15 (n = 7) or 120 mg (n = 8) of beta-carotene daily for four weeks while continuing the same diet. Serum beta-carotene and breath pentane were measured before and after beta-carotene refeeding. Lipid peroxidation, as assessed by gas-chromatographic measurement of breath pentane, was significantly (p < 0.05) reduced by daily supplements of 120 mg beta-carotene (from 3.7 +/- 0.9 to 2.2 +/- 1.4 nmol/l). However, the decline in pentane exhalation observed with the 15-mg beta-carotene dose did not achieve statistical significance (p = 0.13).

Adult↗