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Biomedical subjects

M J Lawson

Publications and source records attributed to M J Lawson.

At least 19 recordsLinked to original sources
PubMed1995

Colorectal cancer and noncancer patients have similar labeling indices by microscopy and computed image analysis.

The labeling index (LI), a microscopic measurement of proliferative activity in colonic crypts, is proposed as an indicator of colonic cancer risk. Computed image analysis of proliferative regions is less labor intensive and more objective than is direct microscopy but has not been validated for labeling indices by direct comparison. The authors compared colonic crypt proliferation in 26 cancer and 13 noncancer patients by using Ki-67 monoclonal antibody (McAb) labeling of flat mucosa obtained from surgically removed, frozen specimens. In cancer patients, the mucosa specimen was excised 10 cm away from the tumor, and the LI was determined microscopically for the whole crypt, the upper two thirds, and the upper one third of 15 crypts. Nuclear antigen levels of 15 whole crypts were determined by using the CAS-200 computed image analyzer (Cell Analysis Systems, Elmhurst, IL). Cancer and noncancer specimens were compared as were microscopically determined LI and stained nuclei specimens by using image analysis. No statistically significant difference in proliferative activity of whole crypts, or the upper two thirds of crypts, was observed between cancer specimens and noncancer specimens from using either technique. However, a significant correlation existed between microscopic analysis and computed image analysis of labeled nuclei. Computed image analysis using Ki-67 McAb labeling can be used instead of microscopy to determine crypt LI, but neither method can be used to distinguish cancer specimens from noncancer specimens.

Adenocarcinoma↗
PubMed1992

Colorectal cancer. Identifying and screening high-risk patients.

Colorectal carcinoma is a major cause of cancer-related morbidity and mortality in the United States. High-risk patients should be appropriately identified and screened. Current recommendations from the American Cancer Society for the average-risk patient include both digital rectal examination and fecal occult blood testing annually beginning at age 40, as well as flexible sigmoidoscopy every 3 to 5 years beginning at age 50 after two normal annual examinations. If any of these tests yield positive results, complete examination of the colon with colonoscopy is indicated. The reliability, sensitivity, and cost-effectiveness of both digital examinations and stool occult blood testing have not been reported to be adequate for screening large populations. A more practical approach may be to omit stool testing and recommend screening with flexible sigmoidoscopy for average-risk patients aged 50 and older. Patients with distal adenomas should undergo colonoscopy and polypectomy as necessary, with follow-up colonoscopy determined by the number of polyps and success in removal.

Colonoscopy↗
PubMed1990

Nitrite from inflammatory cells--a cancer risk factor in ulcerative colitis?

Elevated levels of luminal nitrite and a lowered luminal pH were found in 77 percent of patients with acute ulcerative colitis. No luminal nitrite was found in healthy control subjects. Nitrites are a secretory product of activated macrophages and neutrophils of the lamina propria, whereas the lowered luminal pH is due to diminished bicarbonate formation by impaired colonocytes. A hypothesis is put forward that nitrites, lowered pH, and bacterial amines are conducive to formation of carcinogenic n-nitroso compounds, which reflect a cancer risk in patients with ulcerative colitis dependent on the type and extent of inflammatory cell activation as well as metabolic impairment of colonic epithelial cells.

Animals↗
PubMed1990

Pentose phosphate pathway in rat colonic epithelium.

The colonic cells of the large intestine are one of the most proliferative tissues of the animal body. The pentose pathway has an essential role in cell division and growth being the only pathway forming ribose 5-P necessary for all nucleotide and nucleic acid sunthesis. The pentose pathway may also provide reducing potential as NADPH for biosynthesis and C-3- C-8 glycolyl compounds. The maximum catalytic capacities of the reactions of the non-oxidative pentose pathway for the conversion of ribose 5-P to hexose and triose phosphates by the proximal and distal colon under feeding and starvation regimes are among the highest in the animal body. The qualitative presence of the oxidative pentose pathway was assessed by measurement of the C-1/C-6 ratio value of 1.67-1.82. Enzymes of the F-type and L-type pentose pathways are present in colonocytes and their maximum catalytic activities in colonocyte cytosol are reported. The contribution of the F-type pentose cycle to the total glucose metabolism of colonocytes, measured by the specific yield method, is negligibly low (approximately 1.5%). Colonic epithelial cells use glucose at a high rate (7.1 +/- 0.33 mumol min-1g-1 dry wt) and 79% of the glucose is converted to lactate. Arabinose 5-P has an intermediary role in the formation of keto pentose, sedoheptulose and hexose phosphates from ribose 5-P by colonocyte cytosol. The intermediary and reaction products of [1-13C] ribose 5-P dissimilation by colonocytes is investigated by 13C NMR spectroscopy. The 13C positional isotope distributions show labelling of C-1 and C-3 of hexose 6-phosphates consistent with either the theoretical predictions of the F-type pentose pathway or of the activities of exchange reactions catalysed by transketolase and/or transaldolase. Measurements of exchange reactions showed that the C-1/C-3 labelling of these compounds is mostly, if not wholly, attributable to exchange catalysis by these group transferring enzymes. The results suggest that the F-type PC has little role in the glucose metabolism of colonocytes and pentose phosphate formation may thus occur by a contribution (approx 20% of the total glucose metabolism) by the alternate L-type pathway.

Animals↗
PubMed1989

An assessment of proliferative and enzyme activity in transitional mucosa adjacent to colonic cancer.

The mucosa within 2 cm of cancers of the large bowel (transitional mucosa) shows histologic and histochemical changes which may indicate premalignant change. In this study, the authors used specimens from resected colonic tissue to compare morphometric, proliferative, and enzyme markers in transitional mucosa with those in cancer tissue and with those in uninvolved mucosa at least 10 cm from the cancer. Proliferative activity was assessed using the Ki 67 monoclonal antibody technique whereas a variety of methods were used to determine enzyme activities in mucosal homogenates. When compared to uninvolved mucosa, crypts in transitional mucosa contained greater number of cells, were significantly deeper and wider and were more likely to be branched. However, crypts in transitional mucosa had a significantly lower labelling index using the Ki 67 technique and there was no evidence of a shift in the proliferative zone towards the bowel lumen. The activities of ornithine decarboxylase, thymidine kinase, alkaline phosphatase, and lactate dehydrogenase were similar in transitional and uninvolved mucosa. Cancer tissue showed significantly higher levels of activity for ornithine decarboxylase and lactate dehydrogenase. Transitional mucosa showed morphometric changes but there were no proliferative or enzyme markers to suggest a higher than expected risk for malignant change.

Alkaline Phosphatase↗
PubMed1989

Effects of training in use of executive strategies on a verbal memory problem resulting from closed head injury.

This case study reports attempts to improve the recall performance of an adolescent (GC) who had suffered a closed-head injury. GC had a very limited range of ways of processing both spoken and written information and showed significant recall problems. Initial training in the use of strategies for list learning resulted in improvement in paired-associate recall but showed that initiation and use of the newly learned strategies would not occur without prompting. Executive strategy training was provided to improve GC's ability to identify a memory problem and to initiate a general plan for dealing with that problem. This training involved consideration of task analysis, strategy selection and initiation, and monitoring of strategy use. Evidence of long-term maintenance of improvement in level of recall on both paired-associate and free recall tests was noted following the executive strategy training.

Adolescent↗
PubMed1988

Zinc deficiency is associated with suppression of colonocyte proliferation in the distal large bowel of rats.

As zinc status may influence susceptibility to colon cancer, we examined the effect of dietary zinc deficiency on the proliferation of epithelial cells (colonocytes) in the large bowel of rats. When compared to feed-restricted rats, those with zinc deficiency showed a significant reduction in proliferation in the distal colon as assessed by accumulated metaphase arrest and crypt cell production rates in vivo. Zinc deficiency had no apparent effect on thymidine kinase activity in colonocytes but was accompanied by minor changes in fecal mass and fecal pH. In rats, zinc deficiency is associated with a reduction in the rate of proliferation of colonocytes in the distal colon.

Animals↗
PubMed1988

Proliferative activity in the proximal and distal colon of the rat after fasting and refeeding.

Several methods were used to assess proliferation of colonocytes in the proximal and distal colon of the rat after fasting and refeeding. Those applied in vivo included metaphase arrest, labelling with bromodeoxyuridine and uptake of tritiated thymidine. The latter two techniques were also applied after isolation of colonocytes in vitro. Methods applied in vivo showed similar proliferation in the proximal and distal colon after fasting and enhanced proliferation in both regions after refeeding. However, the degree of enhancement was greater in the distal colon than in the proximal colon. In vitro, proliferation was enhanced in both the proximal and distal colon after refeeding but the degree of variability was greater than after assessment in vivo. Methods applied in vivo are preferred for assessment of proliferative activity in the rat colon, and major changes in proliferation in both proximal and distal colon can be induced by fasting-refeeding.

Animals↗
PubMed1986

Neurologic syndrome associated with low levels of vitamin E in primary biliary cirrhosis.

A 41-yr-old woman with primary biliary cirrhosis developed weakness and wasting in proximal muscles, areflexia, and decreased proprioceptive and vibratory sensation. Investigations revealed law serum levels of vitamin E and electromyographic and muscle biopsy changes consistent with a neuropathy. Sural nerve histology demonstrated axonal dystrophy with patchy demyelination. These features closely resemble a neurologic syndrome associated with chronic cholestatic liver disease and vitamin E deficiency in children. Adults with chronic cholestasis may also be susceptible to neurologic damage from prolonged malabsorption of vitamin E.

Adult↗
PubMed1986

Antral gastrin concentrations in duodenal ulcer patients after cimetidine and highly selective vagotomy.

Post-prandial serum levels of gastrin, the main hormonal stimulator of acid secretion, have been shown to be significantly elevated after HSV compared with controls. The mechanism for this elevation is not known but could be secondary to an increased antral gastrin concentration (AGC). In this study AGCs were measured in endoscopic biopsies before and at intervals of 6 and 32 weeks after HSV in 12 patients with duodenal ulcer. Results were compared with 13 normal controls and 12 duodenal ulcer patients treated with cimetidine for 6 weeks. Blood was taken for fasting serum gastrin concentration at each endoscopy. In the HSV group AGC significantly increased on both postoperative occasions when compared with pre-operative values (P less than 0.01). AGC also showed a significant correlation with time after HSV (r = 0.71; P less than 0.01). Only one patient, who had a persistent duodenal ulcer, failed to show an increase in AGC. Cimetidine failed to increase AGCs in duodenal ulcer patients after 6 weeks of treatment. However, a subgroup (n = 7) of cimetidine-treated patients with low pretreatment AGCs, below 10 ng/mg, did show a significant rise at 6 weeks (P less than 0.05). Fasting serum gastrin levels did not change significantly in any of the three groups. It is concluded that HSV causes a significant increase in AGC with time.

Adult↗
PubMed1986

Detectable colonic nitrite levels in inflammatory bowel disease--mucosal or bacterial malfunction?

In the healthy colon, sodium nitrite stimulates mucosal metabolism of short-chain fatty acids and absorption of ions, both functions that are impaired in the mucosa of patients with ulcerative colitis (UC). To assess the role of nitrite in colonic inflammatory disease, sodium nitrite was measured in rectal dialysate of 49 subjects (18 controls, 23 UC and 8 other colitis). None of the control or quiescent UC patients had measurable levels of nitrite while 78% of patients with acute UC and 38% of patients with other colitis had measurable nitrite levels (acute UC vs. other colitis chi 2 = 5.555, p less than 0.02). Functional activity of the colonic mucosa, judged by bicarbonate output, was impaired in all subjects with measurable nitrite levels in UC. Detection of nitrite in acute colitis suggests impaired oxidation of nitrite to nitrate in the colonic mucosa or impaired luminal reduction of nitrite to NH4 by bacteria.

Ammonia↗
PubMed1985

Observing executive activity in a simple assembly task.

Performance of a group of adult trainees in a workshop for mentally retarded persons and that of an equivalent-MA group of third-grade children was observed in a toy construction task. Performances were video taped and subsequently coded for executive activity and other classes of behavior. A range of executive activities was identified, and these proved to be a powerful influence in discriminating between the groups. Other analyses of event sequences examined where executive activity occurred and which types of events typically followed such activity.

Adult↗
PubMed1984

Clinical evaluation of the 14C-Triolein Breath Test: a critical analysis.

Twenty-two hospital patients without gastrointestinal symptoms and fourteen patients with clinically suspected fat malabsorption were studied using the 14C-Triolein Breath Test and three day fecal fat estimation. The 14C-Triolein Breath Test was 100% sensitive and 86% specific for fat malabsorption. Three day fecal fat estimations were 86% sensitive and 91% specific. These data confirm the high sensitivity and specificity obtained using the 14C-Triolein Breath Test. The speed and convenience of the 14C-Triolein Breath Test plus acceptable sensitivity and specificity make this a practical screening test to detect fat malabsorption.

Adult↗