Polyamine research in plants – a changing perspective

Our understanding of the precise role(s) of polyamines (PAs) in various plant developmental and morphogenetic processes has advanced considerably by the ability to manipulate PA biosynthetic pathways using polyamine biosynthesis inhibitors, PA- mutants and by adopting various transgenic strategies. The cDNA for almost every biosynthesis pathway enzyme has been isolated and cloned in a number of systems. This review briefly summarizes our current understanding of the genetic control of PA metabolism in different model plant systems.     

Nature of light requirement for the flowering of Chenopodium rubrum L. (Ecotype 60° 47′N)

It has been shown that induction of flowering in Chenopodium rubrum L. (ecotype 60° 47 N) seedlings in BCJ light conditions is intensity dependent (Cumming, 1969, Canad. J. Bot. 47, 1247–1250) and that, this intensity dependence is not based on photosynthesis (Sawhney and Cumming, 1971, Can. J. Bot. 49, 2133–2137). Since BCJ light emits a high proportion of energy in the far-red, and the High Energy Reaction (HER) has its action maxima in the far-red and blue regions of the spectrum, we tested the involvement of HER in the light induction of flowering in C. rubrum. Our results show that optimum intensities of blue light are effective in inducing flowering in C. rubrum. Red light exposure does not lead to flower induction. We suggest the HER may be involved in the flower induction of C. rubrum in light. However, when high energy in blue and/or farred is provided in presence of energy between 500–700 nm wavebands, there is no flowering in C. rubrum. We suggest that flower inducing activity of HER may be counteracted by flower inhibitory action of red wavebands.This paper constitutes a part of a Ph. D. thesis submitted to the University of Western Ontario, London, Ontario     

Polyamines in plant physiology

The diamine putrescine, the triamine spermidine, and the tetramine spermine are ubiquitous in plant cells, while other polyamines are of more limited occurrence. Their chemistry and pathways of biosynthesis and metabolism are well characterized. They occur in the free form as cations, but are often conjugated to small molecules like phenolic acids and also to various macromolecules. Their titer varies from approximately micromolar to more than millimolar, and depends greatly on environmental conditions, especially stress. In cereals, the activity of one of the major polyamine biosynthetic enzymes, arginine decarboxylase, is rapidly and dramatically increased by almost every studied external stress, leading to 50-fold or greater increases in putrescine titer within a few hours. The physiological significance of this increase is not yet clear, although most recent work suggests an adaptive, protective role. Polyamines produced through the action of ornithine decarboxylase, by contrast, seem essential for DNA replication and cell division. The application of exogenous polyamines produces effects on patterns of senescence and morphogenesis, suggesting but not proving a regulatory role for polyamines in these processes. The evidence for such a regulatory role is growing.     

Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: Analysis of survival and prognostic markers

Introduction

Male breast cancer (MBC) is a rare, yet potentially aggressive disease. Although literature regarding female breast cancer (FBC) is extensive, little is known about the etiopathogenesis of male breast cancer. Studies from our laboratory show that MBCs have a distinct immunophenotypic profile, suggesting that the etiopathogenesis of MBC is different from FBCs. The aim of this study was to evaluate and correlate the immunohistochemical expression of cell cycle proteins in male breast carcinoma to significant clinico-biological endpoints.

Methods

75 cases of MBC were identified using the records of the Saskatchewan Cancer Agency over 26 years (1970-1996). Cases were reviewed and analyzed for the immunohistochemical expression of PCNA, Ki67, p27, p16, p57, p21, cyclin-D1 and c-myc and correlated to clinico-biological endpoints of tumor size, node status, stage of the disease, and disease free survival (DFS).

Results

Decreased DFS was observed in the majority of tumors that overexpressed PCNA (98%, p = 0.004). The overexpression of PCNA was inversely correlated to the expression of Ki67 which was predominantly negative (78.3%). Cyclin D1 was overexpressed in 83.7% of cases. Cyclin D1 positive tumors were smaller than 2 cm (55.6%, p = 0.005), had a low incidence of lymph node metastasis (38.2%, p = 0.04) and were associated with increased DFS of >150 months (p = 0.04). Overexpression of c-myc (90%) was linked with a higher incidence of node negativity (58.3%, p = 0.006) and increased DFS (p = 0.04). p27 over expression was associated with decreased lymph node metastasis (p = 0.04). P21 and p57 positive tumors were related to decreased DFS (p = 0.04). Though p16 was overexpressed in 76.6%, this did not reach statistical significance with DFS (p = 0.06) or nodal status (p = 0.07).

Conclusion

Aberrant cell cycle protein expression supports our view that these are important pathways involved in the etiopathogenesis of MBC. Tumors with overexpression of Cyclin D1 and c-myc had better outcomes, in contrast to tumors with overexpression of p21, p57, and PCNA with significantly worse outcomes. P27 appears to be a predictive marker for lymph nodal status. Such observation strongly suggests that dysregulation of cell cycle proteins may play a unique role in the initiation and progression of disease in male breast cancer. Such findings open up new avenues for the treatment of MBC as a suitable candidate for novel CDK-based anticancer therapies in the future.     

Comparison of Glucose Lowering Effect of Metformin and Acarbose in Type 2 Diabetes Mellitus: A Meta-Analysis

BackgroundMetformin is the first-line oral hypoglycemic agent for type 2 diabetes mellitus recommended by international guidelines. However, little information exists comparing it with acarbose which is also commonly used in China. This study expanded knowledge by combining direct and indirect evidence to ascertain the glucose lowering effects of both drugs.MethodsPubMed (1980- December 2013) and China National Knowledge Infrastructure databases (1994-January 2014) were systematically searched for eligible randomized controlled trials from Chinese and English literatures. Meta-analysis was conducted to estimate the glucose lowering effects of metformin vs. acarbose, or either of them vs. common comparators (placebo or sulphonylureas), using random- and fixed-effect models. Bucher method with indirect treatment comparison calculator was applied to convert the summary estimates from the meta-analyses into weighted-mean-difference (WMD) and 95% confidence intervals (CIs) to represent the comparative efficacy between metformin and acarbose.ResultsA total of 75 studies were included in the analysis. In direct comparison (8 trials), metformin reduced glycosylated hemoglobin (HbA_1c) by 0.06% more than acarbose, with no significant difference (WMD,-0.06%; 95% CI, -0.32% to 0.20%). In indirect comparisons (67 trials), by using placebo and sulphonylureas as common comparators, metformin achieved significant HbA_1c reduction than acarbose, by -0.38% (WMD,-0.38%, 95% CI, -0.736% to -0.024%) and -0.34% (WMD, -0.34%, 95% CI, -0.651% to -0.029%) respectively.ConclusionThe glucose lowering effects of metformin monotherapy and acarbose monotherapy are the same by direct comparison, while metformin is a little better by indirect comparison. This implies that the effect of metformin is at least as good as acarbose''s.     

Insulin secretion at high altitude in man

The effect of hypoxia on circulatory levels of insulin, its response to oral glucose administration (100 g) and changes in circadian rhythms of glucose as well as insulin were evaluated in euglycemic males at sea level (SL, 220 m) during their stay at high altitude (3500 m, SJ) and in high altitude natives (HAN).Basal glucose levels were not altered at high altitude but the rise in glucose ( glucose) after glucose load was significantly higher in SJ and HAN (p<0.01) as compared to SL values. An increase (p<0.01) both in basal as well as glucose induced rise in insulin secretion ( insulin) was observed at HA. The rise in insulin in SJ was significantly higher (p<0.01) than in HAN. This elevation in glucose and insulin levels was also evident at different times of the day. The circadian rhythmicity of glucose as well as insulin was altered by the altitude stress. The findings of the study show a rise in insulin level at HA but the hyperglycemia in the face of hyper-insulinism require the presumption of a simultaneous and dispropotionate rise of insulin antagonistic hormones upsetting the effect of insulin on glucose metabolism.Presented at International Conference of Biometeorology held at New Delhi from December 26–30, 1983.     

Thyroid gland function during cross adaptation to heat and cold in man

Plasma thyroxine (T₄), triiodothyronine (T₃) and thyrotropin (TSH) levels were monitored in 10 healthy euthyroid male subjects of the age group 20 to 30 years before and during heat and cold acclimatisation schedule in a sequential manner. The subjects were exposed to 45C DB and 30% relative humidity in a hot chamber for 2 hours daily for 8 consecutive days. Subsequently they were exposed to cold for 4 hours daily at 10C for 21 days. The mean plasma T₄ and T₃ concentration before exposure to heat were 7.87±0.82 ug/dl and 159.8±9.1 ng/dl respectively. A significant decrease in both T₄ (p<0.05) and T₃ (p<0.01) levels to mean values of 6.4±0.76g/dl and 129±7.9 ng/dl was recorded on day 4 of exposure to heat. Further significant decrease (p<0.05) over the preceding T₃ levels was observed on day 8 of heat exposure. Plasma T₄ and T₃ on day 21 of cold exposure was not significantly different from the levels reckoned after last day of heat exposure but was significantly lower than the pre-exposure values. Throughout the thermal stress schedule there was no change in the TSH levels. These observations suggest that a decrease in thyroid hormone levels during exposure to heat might be an adaptive process which continues even during cold acclimatisation.     

Thidiazuron-induced hypertrophic growth from foliar disks of <Emphasis Type="Italic">Kalanchoe pinnata</Emphasis> leads to visualization of a bioactive auxin gradient across the leaf plane

Thidiazuron induces a variety of effects in foliar explants of K. pinnata cultured in vitro. Of these, the induction of an organized hypertrophic growth at the vein ending on the proximal side of leaf disks is a significant morphogenetic effect. This polarized hypertrophy is considered an exclusive auxin-mediated response, as the effect is completely reversed by auxin efflux inhibitor 2,3,5-triiodobenzoic acid. With the magnitude of hypertrophic growth from individual disks taken as a manifestation of putative auxin levels, the occurrence of a gross, decreasing bioactive auxin gradient from median-basal to peripheral locations across the leaf plane has been observed.