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Biomedical subjects

M R Lewin

Publications and source records attributed to M R Lewin.

At least 19 recordsLinked to original sources
PubMed2001

Defensive responses of larval Manduca sexta and their sensitization by noxious stimuli in the laboratory and field.

Sensitization of defensive responses following noxious stimulation occurs in diverse species, but no demonstration of nociceptive sensitization in insects has been reported. A set of defensive behavior patterns in larval Manduca sexta is described and shown to undergo sensitization following noxious mechanical stimulation. The striking response is a rapid bending that accurately propels the head towards sharply poking or pinching stimuli applied to most abdominal segments. The strike is accompanied by opening of the mandibles and, sometimes, regurgitation. The strike may function to dislodge small attackers and startle larger predators. When the same stimuli are applied to anterior segments, the head is pulled away in a withdrawal response. Noxious stimuli to anterior or posterior segments can evoke a transient withdrawal (cocking) that precedes a strike towards the source of stimulation and may function to maximize the velocity of the strike. More intense noxious stimuli evoke faster, larger strikes and may also elicit thrashing, which consists of large, cyclic, side-to-side movements that are not directed at any target. These are sometimes also associated with low-amplitude quivering cycles. Striking and thrashing sequences elicited by obvious wounding are sometimes followed by grooming-like behavior. Very young larvae also show locomotor responses to noxious stimuli. Observations in the field of attacks on M. sexta larvae by Cardinalis cardinalis, an avian predator, suggest that thrashing decreases the success of a bird in biting a larva. In the laboratory, noxious stimulation was found to produce two forms of sensitization. Repeated pinching of prolegs produces incremental sensitization, with later pinches evoking more strikes than the first pinch. Brisk pinching or poking of prolegs also produces conventional sensitization, in which weak test stimuli delivered to another site evoke more strikes following noxious stimulation. The degree and duration of sensitization increase with more intense noxious stimulation. The most intense stimulus sequences were found to enhance strike frequency for approximately 60 min. Nociceptive sensitization generalizes to sites distant from sites of noxious stimulation, suggesting that it involves a general, but transient, arousal of defensive responses. http://www.biologists.com/JEB/movies/jeb3271.html

Animals↗
PubMed2000

Duodenal ulcer prevalence: experimental evidence for the possible role of dietary lipids.

BACKGROUND AND AIMS: Mapping the geographical distribution of duodenal ulcer in relation to staple diets, and experiments on animal peptic ulcer models suggested that the lipid fraction in certain foodstuffs had a protective effect which was most marked in the lipid obtained from Horse gram (Dolichos biflorus). Lipid obtained from stored polished rice or rice bran was ulcerogenic. Further animal experiments were designed to investigate the protective and healing effects of Horse gram lipid (HGL) against peptic ulceration. METHODS: Three effects were investigated in rats: (i) the protective effect of HGL on peptic ulceration produced by using pyloric ligation in combination with South Indian diet or rice bran oil, or by cysteamine, alcohol or aspirin; (ii) the effect of HGL on mast cell degranulation in response to pyloric ligation and rice bran oil; and (iii) the healing effect of HGL on acute gastric ulceration produced by alcohol, on chronic gastric ulceration produced by topical acetic acid or on chronic duodenal ulcer following cysteamine. RESULTS: Horse gram lipid was shown to be protective and to promote ulcer healing in all the models used. Mast cell degranulation was inhibited. CONCLUSION: The experiments confirm the presence of a lipid in certain staple foods that have protective and healing properties in experimental peptic ulcer animal models. The differences in the prevalence of duodenal ulceration between different regions in some developing countries with a high prevalence of Helicobacter pylori infection might be explained by the presence or absence of protective lipids or ulcerogenic factors in the staple diet.

Acetic Acid↗
PubMed2000

Intractable nausea, vomiting and diarrhea in a Mexican woman with No recent travel history.

A 45-year-old Mexican woman with a history of noninsulin dependent diabetes mellitus (NIDDM), hypertension, and coronary artery disease presented to the hospital after 2 months of intractable nausea, vomiting and diarrhea-all made worse by eating and drinking. She reported fever, chills, anorexia and a documented 50-pound weight loss during this period. She denied the signs and symptoms of melena, hematochezia, steatorrhea or constipation. She also reported left leg pain and decreased sensation and strength of her left leg compared to the right leg. She had been hospitalized 2 weeks prior to admission with the same symptoms and a diagnosis of viral gastroenteritis. She was also treated for H. pylori, but subsequent biopsy results were negative by Steiner stain.

Adrenal Cortex Hormones↗
PubMed1999

Activation of protein kinase A contributes to the expression but not the induction of long-term hyperexcitability caused by axotomy of Aplysia sensory neurons.

Nociceptive sensory neurons (SNs) in Aplysia provide useful models to study both memory and adaptive responses to nerve injury. Induction of long-term memory in many species, including Aplysia, is thought to depend on activation of cAMP-dependent protein kinase (PKA). Because Aplysia SNs display similar alterations in models of memory and after nerve injury, a plausible hypothesis is that axotomy triggers memory-like modifications by activating PKA in damaged axons. The present study disproves this hypothesis. SN axotomy was produced by (1) dissociation of somata from the ganglion [which is shown to induce long-term hyperexcitability (LTH)], (2) transection of neurites of dissociated SNs growing in vitro, or (3) peripheral nerve crush. Application of the competitive PKA inhibitor Rp-8-CPT-cAMPS at the time of axotomy failed to alter the induction of LTH by each form of axotomy, although the inhibitor antagonized hyperexcitability produced by 5-HT application. Strong activation of PKA in the nerve by coapplication of a membrane-permeant analog of cAMP and a phosphodiesterase inhibitor was not sufficient to induce LTH of either the SN somata or axons. Furthermore, nerve crush failed to activate axonal PKA or stimulate its retrograde transport. Therefore, PKA activation plays little if any role in the induction of LTH by axotomy. However, the expression of LTH was reduced by intracellular injection of the highly specific PKA inhibitor PKI several days after nerve crush. This suggests that long-lasting activation of PKA in or near the soma contributes to the maintenance of long-term modifications produced by nerve injury.

Animals↗
PubMed1999

Cyclic GMP pathway is critical for inducing long-term sensitization of nociceptive sensory neurons.

Noxious stimulation can trigger persistent sensitization of somatosensory systems that involves memory-like mechanisms. Here we report that noxious stimulation of the mollusc Aplysia produces transcription-dependent, long-term hyperexcitability (LTH) of nociceptive sensory neurons that requires a nitric oxide (NO)-cyclic GMP-protein kinase G (PKG) pathway. Injection of cGMP induced LTH, whereas antagonists of the NO-cGMP-PKG pathway prevented pinch-induced LTH. Co-injection of calcium/cAMP-responsive-element (CRE) blocked both pinch-induced LTH and cAMP-induced LTH, but antagonists of protein kinase A (PKA) failed to block pinch-induced LTH. Thus the NO-cGMP-PKG pathway and at least one other pathway, but not the cAMP-PKA pathway, are critical for inducing LTH after brief, noxious stimulation.

Animals↗
PubMed1991

Is there a fibre-depleted aetiology for colorectal cancer? Experimental evidence.

In 1971, Denis Burkitt put forward his now famous hypothesis of a fibre-depleted aetiology for colorectal cancer. This was based on his careful clinical observations of the difference in patterns of diseases between Western and traditional African societies. He noted the rarity of colorectal cancer in African countries compared to the West and found that African diets were generally higher in dietary fibre and lower in refined carbohydrates. Since these pioneering observations there have been numerous epidemiological studies but many have failed to support Burkitt's attractive hypothesis. The purpose of this review is to examine the role of dietary fibre in the animal model of colon cancer and to assess critically the findings in the light of current knowledge of the theory of carcinogenesis. The findings from the studies of the experimental model of colon cancer did not support the theory of a fibre-depleted diet as a causative factor in the aetiology of colorectal cancer in man. However, the experimental evidence did suggest that an increase in dietary fibre does have a role in protection from this disease. It was concluded that in colorectal cancer, the effect of a fibre-depleted diet was through a mechanism of promotion (co-carcinogenesis) and that the protective effect of a high fibre diet was by an anticarcinogenic mechanism.

Animals↗
PubMed1990

Direct measurement of collagenase in colonic anastomosis.

Collagenase has been implicated in colonic anastomotic dehiscence but the enzyme has not previously been specifically measured in colonic healing. A 72 h tissue culture method for colonic tissue and a radiochemical assay for collagenase were adapted to measure the enzyme in healing rabbit colon, with specificity of the assay confirmed by sodium dodecylsulphate polyacrylamide gel electrophoresis. Normal and postoperative colon secreted collagenase, predominantly in a latent form, in the first 24 h of culture. Total activity reached a plateau after 48 and 72 h in culture, when 50-70 per cent of the enzyme was in an active form. At these times in culture, activity was significantly higher than after 24 h (P less than 0.001). One day after anastomosis the total amount of collagenase secreted in culture was higher than normal but the increase did not achieve significance. Three days after anastomosis the colon secreted more collagenase than explants from 1 day postoperative tissue (P less than 0.002). The proportion of active enzyme in the first 24 h in culture was also increased. Since active collagenase can be measured in culture medium from both normal and postoperative colon, the tissue may be secreting plasminogen activator which allows plasmin to activate the enzyme. The increase in collagenase after operation coincided with a decrease in collagen concentration in the colon wall, measured by hydroxyproline. This supports previous suggestions that collagenase contributes to anastomotic dehiscence. However, the findings must be interpreted with caution as the variance of the results was shown to be predominantly due to time in culture, suggesting this could be a bigger influence than the operation itself. In addition, our previously reported immunohistochemical study of this system indicated that collagenase only occurred in a localized region, restricted to the everted portion of the anastomosis, with the activity being tightly controlled by its inhibitor, tissue inhibitor of metalloproteinases.

Anastomosis, Surgical↗
PubMed1990

A gastrectomy population: 25-30 years on.

Prior to 1960 a Polya gastrectomy was the most frequent operation for duodenal ulcer. The majority of these patients now have reached the age of sixty or older. A prospective longitudinal study of a cohort of patients who underwent gastrectomy between 1955 and 1960 was undertaken. Twenty five to thirty years later the study has revealed the extent of the nutritional problems that may arise with the passage of time and shows that these numerically far outweigh the mechanical post-gastrectomy syndromes and weight loss which tended to dominate the earlier post-gastrectomy scene. By the end of the first decade, iron deficiency was the commonest nutritional problem. Vitamin B12 deficiency assumed more importance in the second decade. During the third decade both reached equal prevalence, being found in some 90% of the female and 70% of the male residual population. Vitamin D deficiency and early osteomalacia was a lesser problem, reaching its climax in the second decade. Evidence suggested a high incidence of osteoporosis and this requires further investigation. Overall, women fared worse than men with a higher and earlier incidence of iron deficiency, particularly in the pre-menopausal group. This study emphasizes the increasing need for regular screening of post-gastrectomy patients to detect early iron, vitamin B12 and vitamin D deficiencies as patients grow older.

Celiac Disease↗
PubMed1990

The relationship of plasminogen activators and oncogenes to tumour invasion.

Accruing evidence suggests an association between increased activity of plasminogen activators and transformed cells, and urokinase activity with tumour aggressiveness. The PIP2 pathway seems to provide a link between oncogene-associated transformation, cellular proliferation, plasminogen-activator expression and tumour invasion and metastasis.

Cell Division↗
PubMed1989

Differences in mucosal appearances and in relapse rates in duodenal ulceration treated with sucralfate or cimetidine.

A total of 46 patients with duodenal ulcer were randomly assigned, without the knowledge of the investigators, to treatment with cimetidine 200 mg three times daily and 400 mg at night or sucralfate 1 g four times daily followed by one year of maintenance treatment with cimetidine 400 mg at night or sucralfate 1 g twice daily, respectively, in those patients with healed ulcers. The endoscopic healing rates and relapse rates during the maintenance period were similar, four relapses occurring in each group. All four relapses in the sucralfate group occurred at 12 months and only two were symptomatic. All the cimetidine relapses were symptomatic, two occurring at six months, one at nine months, and one at 12 months. Following the one year maintenance period, 13 cimetidine patients and 11 sucralfate patients were followed up for 36 months. During the first two years, nine of 13 (69 percent) cimetidine-treated and two of 11 (18 percent) sucralfate-treated patients had relapses. During the third year, three more sucralfate-treated patients and one more cimetidine-treated patient had relapses, making a total of 10 of 13 (77 percent) and five of 11 (45 percent) in the cimetidine and sucralfate groups, respectively. Duodenal biopsy specimens obtained before and after healing and after one year of maintenance were examined by light and electron microscopy. The sucralfate group showed greater improvement after one year of maintenance therapy than did the cimetidine group, although the appearances in either group were not predictive of subsequent relapse. The results show that relapses are less frequent and occur later after sucralfate therapy and also that the morphologic appearances are more normal after treatment with sucralfate than after treatment with cimetidine.

Adolescent↗
PubMed1989

Leucine kinetics in surgical patients. I: A study of the effect of surgical 'stress'.

At present there is no consensus about the effect of surgical and accidental trauma on protein metabolism. Leucine kinetics, an index of protein turnover, have been studied in ten patients before intra-abdominal surgery and on either the third (n = 5) or seventh (n = 5) postoperative day. Only small changes in leucine kinetics were noted in the early postoperative study but, by the seventh day, there was evidence of increased synthesis as part of an overall elevation of turnover rates. It is suggested that the previously expressed opinion that protein synthesis is reduced after surgery must be re-examined.

Aged↗
PubMed1989

Leucine kinetics in surgical patients. II: A study of the effect of malignant disease and tumour burden.

Isotope studies of protein turnover have given conflicting evidence about the effects of a malignant tumour on the protein metabolism of the host. Leucine kinetics have been studied, as an index of protein turnover, using a well established methodology. Twenty patients were studied, five with benign disease of the colon, ten with localized malignant tumours of the large bowel, and five in whom there was evidence of metastatic disease from a colonic primary. No effect was observed on the leucine turnover of the patients that might be attributable to the presence or size of the tumour burden. It is suggested that some of the previously conflicting results may be attributable to variability in the experimental design, the heterogeneous patient groups studied and the methods used to express the results obtained.

Aged↗
PubMed1989

Effect of nutritional supplementation on protein synthesis in tumour and host tissues of rats with colonic cancer.

Rats with colonic cancer were given a palatable liquid diet which enabled them to gain weight while those fed on stock diet, either ad libitum or in restricted amounts, lost weight. Protein synthesis was measured in vivo using a flooding dose technique. Increased nutrient intake caused increases in the rate of protein synthesis in muscle, liver and non-diseased parts of the colon, but had no effect on protein synthesis in the tumours. These data suggest that enteral hyperalimentation may be safely employed in the preoperative management of patients with cancer, as it is likely to stimulate nitrogen retention in the host tissues without increasing the growth rate of the tumour.

Animals↗