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Biomedical subjects

G Grant

Publications and source records attributed to G Grant.

At least 91 records · Page 5Linked to original sources
PubMed1996

Response of intestinal transglutaminase activity to dietary phytohaemagglutinin.

The behaviour of the activity of tissue transglutaminase, a calcium-dependent enzyme, and the levels of polyamines which are physiological substrates for the enzyme, were studied in rat small intestine induced to grow by lectin phytohaemagglutinin. Transglutaminase activity greatly increased in the homogenates and the cytosolic fractions of the intestinal mucosa of lectin-treated rats compared to that of untreated animals. The measurement of enzyme activity in the presence of monodansylcadaverine, a competitive inhibitor of transglutaminase, testified that the assayed enzyme activity was authentic transglutaminase. As regards polyamines, the level of spermine did not change, whereas putrescine and spermidine contents were enhanced. The activation of transglutaminase, which was probably due to Ca2+ accumulation in enterocytes, could have a role in maintaining enterocyte adhesion and intestinal cell homeostasis, and/or repairing lectin-induced damages of microvilli of the gut epithelium.

Animals↗
PubMed1996

Neurogenesis of subpopulations of rat lumbar dorsal root ganglion neurons including neurons projecting to the dorsal column nuclei.

The time of birth of subpopulations of dorsal root ganglion (DRG) neurons was studied with immunohistochemistry for 5-bromodeoxyuridine (BrdU). Pregnant rats were injected with BrdU i.p. to label the neurons on one of the embryonic days (E) E11-E16. When they were adults, the rats were given injections of Fluoro-Gold (FG) into the gracile nucleus to identify DRG neurons projecting to this structure. Following a 5 day survival period, the animals were perfused with aldehyde fixative. Sections from the L3-L5 DRGs were processed for BrdU immunohistochemistry followed by either immunostaining for the antineurofilament antibody RT97, as marker of the light neuronal subpopulation, or histochemical staining for the B4 isolectin from Griffonia simplicifolia I, as marker of the small dark subpopulation. The results indicated that the DRG neurons were generated between E12 and E16. The RT97+ neurons were generated on E12-E15, with a peak at E13. FG+ neurons, the majority of which were RT97+, were also generated on E12-E15. The B4+ neurons were generated on E13-E16, with a peak around E14. The overall pattern of neurogenesis of the DRG neurons showed that the RT97+ neurons were produced prior to the B4+ neurons. These findings are in agreement with earlier observations that the large DRG neurons are generated earlier than the small dark neurons. Our findings also suggest the existence of a third neuronal subpopulation that might be produced at the latest period of DRG neurogenesis at E15-E16.

Animals↗
PubMed1996

Dietary phytohaemagglutinin slows down the proliferation of a mouse plasmacytoma (MPC-11) tumour in Balb/c mice.

Ten days after subcutaneous injection of MPC-11 cells, plasmacytoma tumours which developed in female Balb/c mice fed on a diet containing the kidney bean lectin phytohaemagglutinin (PHA) at a concentration of 7.0 mg g-1 diet, weighed only about 38% of those fed a lactalbumin (La) control diet. The reduction in growth caused by the lectin appeared to occur in a dose-dependent manner but the values did not reach significance before PHA was at a concentration of 7.0 mg g-1 diet. Pre-feeding with the lectin caused a further 50% reduction in tumour weight. In contrast to the reduction in tumour size the inclusion of PHA in the diet elevated the mean dry weight of the small intestine in a dose-dependent manner, values reaching significance at 3.5 mg g-1 diet. The results showed that gut hyperplasia was able to occur even in the presence of the developing tumour. A lypolytic effect of PHA occurred at high concentration. The observations suggest that PHA itself does not have a direct effect on the tumour cells, but an inter-relationship between gut hyperplasia and decreased tumour growth is indicated.

Animals↗
PubMed1996

The effect of phytohaemagglutinin at different dietary concentrations on the growth, body composition and plasma insulin of the rat.

Young growing rats weighing approximately 83 g were fed on diets containing kidney bean (Phaseolus vulgaris) lectin (phytohaemagglutinin, PHA) in the range of 0-0.45 g/kg body weight for 10 d to ascertain whether there was a minimum dose below which the lectin had no significant effect on body and skeletal muscle weights in comparison with pair-fed lectin-free controls. Averaged over all experiments, PHA doses of less than 10 mg/d (0.12 g/kg body weight) reduced body dry by 1.14 (SE 0.25) g when compared with controls. Between 10 and 27 mg/d (0.12-0.32 g/kg body weight) a further reduction of 0.64 (SE 0.21) g occurred, suggesting a slight but steady decline of body dry weight with increasing dose. However, above 27 mg/d the depression of growth and changes in body composition accelerated. The difference between the proportional losses of skeletal muscle and body weight was not significant at doses of PHA below 10 mg/d (0.12 g/kg body weight) but the ratio of these losses rose to 1.5-2.0 at doses above this. The proportional decrease in lipid weight exceeded that of both body and skeletal muscle weights at all lectin doses, suggesting that lipid catabolism was the first target of the PHA effect. Plasma insulin level was depressed at the PHA dose of 0.02 g/kg body weight at which growth depression and muscle atrophy were minimal but, contrary to expectations, plasma glucose levels remained stable over the whole PHA dose range. It appears that despite a PHA-induced lowering of blood insulin, glucose catabolism is elevated by an unknown, possibly hormonal, compensatory mechanism. Thus, because low insulin levels facilitate the mobilization and catabolism of lipids, it may be possible to use low doses of PHA to reduce hyperglycaemia and body fat.

Animals↗
PubMed1996

A rat model of infection by Salmonella typhimurium or Salm. enteritidis.

Salmonellosis in the rat has many similarities with the disease in humans, with the ileum thought to be the main site of colonization/invasion in both species. Thus, the rat may be a useful way to study the mechanism of infection by these pathogenic bacteria. A series of infection trials carried out with Hooded Lister rats showed that a salmonella infection persisted for an extended period of time and that salmonellae bind to the small intestinal epithelium as early as 4 h after intragastric intubation. Reinfection from the large intestine may not therefore initially play a significant role in the salmonella infection process. The rat model may therefore provide a means to test in vivo interventionist strategies, designed to block binding of the pathogens in the gastrointestinal tract.

Animals↗
PubMed1996

Phytohemagglutinin-induced gut hyperplasia and the growth of a mouse lymphosarcoma tumor.

NMRI mice injected subcutaneously with Krebs II lymphosarcoma cells and fed on a diet containing the kidney bean lectin phytohemagglutinin (PHA) within the range 0.45-7.0 mg/g diet, developed tumors during a 10 day period which on average were only 35% of the dry weight of tumors in lactalbumin (La) fed mice (control). The reduction in growth occurred in a dose-dependent manner in the range 0.45-3.5 mg/g diet. The degree of hyperplasia of the small intestine in response to feeding the PHA diets was higher in non-injected compared to injected mice. A lipolytic effect of PHA was observed above 1.75 mg/g diet in control mice and the highest concentration had a major effect on body weight. Since the index of hyperplasia at the lowest PHA concentration tested did not correlate with the reduction in tumor size, it is suggested that other factors in addition to the initial lectin-induced gut hyperplasia are involved in slowing down the progression of tumor growth.

Animals↗
PubMed1996

The effect of switching between a phytohemagglutinin-containing and a control diet on the growth and lipid content of a Krebs II lymphosarcoma tumor.

The present study concerns the importance of the timing of feeding mice a PHA-containing diet (7 mg g-1 diet) on tumor formation. The major decrease in tumor weight occurred in mice fed on the PHA diet for 11 days. A marked reduction was also observed in animals pre-fed for 3 days with PHA before tumor cells were injected and the diet then changed to lactalbumin, La. A large decrease in tumor weight was also evident when a change of diet from La to PHA was made on the day of tumor cell inoculation. Despite the presence of the developing tumor PHA was able to induce hyperplasia of the small intestine in all groups of animals fed PHA during a part or the whole of the experiment. The dry weights of tumors attained in each of the experimental groups plotted as a function of duration of PHA feeding, and the percentage lipid content of the tumors, mirrored almost exactly one another, suggesting that the availability of essential lipid material is severely reduced by the lectin. This would appear to have a major effect on the observed reduction in tumor growth.

Animals↗
PubMed1995

Ia boutons to CCN neurones and motoneurones are enriched with glutamate-like immunoreactivity.

The monosynaptic connection between muscle spindle Ia afferents and motoneurones is one of the most extensively studied reflex pathways in the central nervous system. Physiological evidence has pointed to glutamate as the fast transmitter in this synaptic connection. In this study of the spinal cord segment C2, we used dual labelling with cholera toxin subunit B-horseradish peroxidase (B-HRP) and postembedding immunohistochemistry to show that group Ia primary afferent boutons synapsing on retrogradely labelled central cervical nucleus (CCN) neurones and motoneurones are enriched in glutamate-like immunoreactivity (LI). All double-labelled Ia terminals studied could be classified as S-type (CCN neurones and motoneurones) or M-type (motoneurones) boutons.

Afferent Pathways↗
PubMed1995

Switching between control and phytohaemagglutinin-containing diets affects growth of Krebs II ascites cells and produces differences in the levels of putrescine, spermidine and spermine.

Almost twice as many ascites tumour cells were recovered from mice pre-fed for 3 days on a lactalbumin (La)-based control diet, injected with Krebs II ascites cells and then maintained on the same diet for a further 8 days, when compared with mice fed on a phytohaemagglutinin-containing (PHA) diet for the whole period. A dietary switch on the day of injection of tumour cells produced an intermediate effect; mice switched to the La diet after pre-feeding on PHA for 3 days developed somewhat more tumour cells than when the opposite dietary switch was performed. The polyamine content in the tumour cells was lowest in the mice fed on La, and highest in mice fed PHA for the duration of the experiment, respectively. Since large amounts of extraneous polyamines are required in order to sustain tumour growth, and the hyperplastic growth of the gut which occurs in response to injesting the lectin is a polyamine-dependent process, it is evident that the two growth signals compete with one another for important nutrients/growth factors, including polyamines.

Animals↗
PubMed1995

Diamine and polyamine oxidase activities in phytohaemagglutinin-induced growth of rat small intestine.

The activities of diamine and polyamine oxidases, two enzymes of polyamine catabolism, were studied in hyperplastic growth of rat small intestine induced by phytohaemagglutinin. This growth, evaluated by the elongation of Lieberkühn's crypts, was more extensive in the proximal than in the distal parts of the gut. The activity of diamine oxidase was significantly reduced in the proximal (70%), medial (45%) and the distal (25%) parts. The activity of polyamine oxidase was doubled. The concentrations of putrescine, cadaverine and spermidine were significantly elevated in the three intestinal parts studied, whereas those of histamine and spermine were unchanged. It appears that changes in the activities of diamine and polyamine oxidases may contribute to the increased putrescine content, which is necessary to maintain active polyamine turnover for sustaining growth of the gut.

Amine Oxidase (Copper-Containing)↗
PubMed1995

Cyclic-AMP deficient MDCK cells form tubules.

It has been known for many years that MDCK cells form blister-like structures, termed domes. During an examination of the morphology of a large number of MDCK clones, we found that two stable morphotypes exist in an MDCK cell population-namely, dome-forming and tubule-forming clones. When maintained at high cell density, tubule-forming clones displayed large numbers of anastomosing tubules which contained lumens. The frequency of observation of the tubule-forming clones in an MDCK population was 0.7%. Tubule-forming MDCK clones should be useful in studying tubule morphogenesis. While agents that affect protein kinase A activity increased dome formation, the same agents abolished the formation of tubules in all tubule-forming clones. In contrast, drugs that stimulate protein kinase C activity (phorbol esters and staurosporine) decreased dome formation an increased tubule morphogenesis in all MDCK morphotypes. Tubule-forming clones were found to have lower resting levels of cyclic-AMP and to respond to forskolin stimulation of adenylate cyclase less readily. Hence, signals transmitted by the protein kinase C pathway appear to lead to tubule formation in MDCK cells, while signals transmitted through the protein kinase A pathway lead to dome formation.

Ammonium Chloride↗
PubMed1995

Lectins and also bacteria modify the glycosylation of gut surface receptors in the rat.

Oral exposure to lectins or the presence or absence of bacteria in the rat small intestine were shown by histological methods using anti-lectin antibodies or digoxigenin-labelled lectins to have major effects on the state of glycosylation of lumenal membranes and cytoplasmic glycoconjugates of epithelial cells. Taken together with the dramatic effects of exposure to lectins on gut function, metabolism and bacterial ecology, this can be used as a basis for new perspectives of biomedical manipulations to improve health.

Administration, Oral↗
PubMed1995

Busy doing nothing: activity and interaction levels amongst differing populations of elderly patients.

This paper considers the activity and interaction levels amongst three differing populations of elderly patients (long-stay, short-stay and respite). It begins with a consideration of the literature on staff-patient interactions in care environments for elderly patients, highlighting the virtual absence of preplanned, purposeful activity. Data are then presented which suggest that, despite the emphasis nurses place on communicating with their patients, many patients continue to spend most of their time inactive. It is suggested that if the quality of care elderly patients receive is to improve, nursing staff must see the provision of activity as an integral part of their role and function.

Activities of Daily Living↗
PubMed1995

The importance of dietary polyamines in cell regeneration and growth.

The polyamines putrescine, spermidine and spermine are essential for cell renewal and, therefore, are needed to keep the body healthy. It was previously believed that polyamines are synthesized by every cell in the body when required. However, in the present paper evidence is provided to show that, as in the case of the essential amino acids, the diet can supply sufficient amounts of polyamines to support cell renewal and growth. Systematic analysis of different foods was carried out and from the data obtained, the average daily polyamine consumption of British adults was calculated to be in the range 350-500 mumol/person per d. The major sources of putrescine were fruit, cheese and non-green vegetables. All foods contributed similar amounts of spermidine to the diet, although levels were generally higher in green vegetables. Meat was the richest source of spermine. However, only a part of the polyamines supplied by the diet is available for use by the body. Based on experiments with rats it was established that polyamines were readily taken up from the gut lumen, probably by passive diffusion, and were partly metabolized during the process of absorption. More than 80% of the putrescine was converted to other polyamines and non-polyamine metabolites, mostly to amino acids. The enzyme responsible for controlling the bioavailability of putrescine was diamine oxidase (EC 1.4.3.6). For spermidine and spermine, however, about 70-80% of the intragastrically intubated dose remained in the original form. Considering the limitations on bioavailability (metabolism and conversion), the amounts of polyamines supplied by the average daily diet in Britain should satisfy metabolic requirements.

Adult↗