Few Canadian hospitals qualify for "Baby Friendly" designation by promoting breast-feeding: survey.

Only five Canadian hospitals meet requirements for promoting breast-feeding as set out by the World Health Organization and qualify to receive the international "Baby Friendly" designation, a national survey has determined. Results from the survey of 523 hospitals were released at a Toronto conference.

Suggested screening guidelines for familial colorectal cancer.

Guidelines for screening for colorectal cancer in subjects with a positive family history of the disease, without the use of DNA based screening, are outlined. These suggestions are derived from (a) the experience of screening 644 subjects at an estimated lifetime risk of dying from colorectal cancer of 10% or more, in the St Mark's Family Cancer Clinic, over six years, and (b) a review of published studies, particularly incorporating the experience of the International Collaboration Group on Hereditary Non-polyposis Colorectal Cancer (HNPCC). Selection of subjects for surveillance depends upon the empirical evaluation of their risk of colorectal cancer, based upon family history details, with the exclusion of a diagnosis of familial adenomatous polyposis in the family.

The role of protein kinase C in arachidonic acid release and prostaglandin E production from CHO cells transfected with EGF receptors.

Arachidonic acid release and prostaglandin production are stimulated by both phorbol esters and growth factors in various cell types. Whereas phorbol esters activate and transmit a signal via protein kinase C, this pathway is not necessarily involved in growth factor signal transduction. We investigated the involvement of protein kinase C in the pathway of arachidonic acid metabolism by CHO cells transfected with full-length EGF receptor (CHOwt).

APC mutation analysis by chemical cleavage of mismatch and a protein truncation assay in familial adenomatous polyposis.

Overall, the causative APC mutation has been identified in only 30% of the patients with familial adenomatous polyposis (FAP) who have been included in studies reported in the literature. In order to determine the true frequency of detectable APC mutations, we set out to search exhaustively the entire coding region of APC for causative mutations in ten patients with classical FAP from Scottish kindreds shown to be linked to 5q markers. Chemical cleavage of mismatch analysis was employed as the initial screening technique.

Deletion analysis of chromosome 8p in sporadic colorectal adenomas.

In order to assess the stage of colorectal tumorigenesis at which chromosome 8p loss of heterozygosity (LOH) occurs, 56 sporadic adenomas were examined for LOH at four polymorphic loci which show frequent LOH in carcinomas. LOH was found in only 5 out of 51 (9.8%) informative adenomas, whereas studies with the same markers in 85 informative carcinomas showed a LOH of 45%.

Genetics of colorectal cancer.

Recent advances in understanding the genetic basis of malignant disease have been dominated by research in colorectal cancer. In familial adenomatous polyposis, characterisation of the causative gene had immediate clinical relevance allowing confident prediction of disease inheritance. Somatic mutations in this gene have been demonstrated to have a fundamental role in the development of sporadic colorectal cancer.

Activation of phospholipase D in CHO cells transfected with the human epidermal growth factor (EGF) receptor: differential effects of protein kinase C activation and EGF.

Multiple intracellular signal transduction pathways, including phospholipases A2 and D, can be activated by epidermal growth factor (EGF) in both a protein kinase C (PKC)-dependent and -independent manner. We investigated the activation of phospholipase D (PLD) by a PKC activator, phorbol myristate acetate (PMA) and by EGF in CHO cells transfected with the full-length EGF receptor. In cells labelled with arachidonic acid or linoleic acid, PMA activated a PLD, determined by formation of the transphosphatidylation product phosphatidylethanol in the presence of ethanol.

Deletion mapping in colorectal cancer of a putative tumour suppressor gene in 8p22-p21.3.

Although previous studies of acquired loss of heterozygosity (LOH) in colorectal tumours have suggested that a tumour suppressor gene may lie within the short arm of chromosome 8, its precise localisation remains to be determined. To obtain a more accurate positional map 120 colorectal cancers were examined with eight chromosome 8 polymorphic markers comprising both restriction fragment length polymorphisms and microsatellite polymorphisms based on (CA)n repeats. 91 cases were informative and LOH was detected in 47 (51%).

Fibronectin-induced increase in mesangial cell prostaglandin release. Effect of hyperglycemia and PKC inhibition.

Glomerular accumulation of extracellular matrix in diabetes is a potential regulator of mesangial cell-matrix interactions through transmembrane matrix receptors. We now provide evidence that PG production from rat glomerular mesangial cells is increased by Fn. An increase in PG (measured as PGE) was demonstrated in mesangial cell-enriched glomerular cores after 1-h exposure (149 +/- 8% of timed control) and was sustained over a 24-h period (214 +/- 7%).

The link between hyperglycaemia and diabetic nephropathy.

A large number of experimental studies in animals and retrospective or non-randomised prospective studies in humans provide support for the concept that the microvascular complications of diabetes mellitus are dependent on hyperglycaemia. This review focuses on four potential biochemical pathways linking hyperglycaemia to changes within the kidney which can plausibly be linked to the functional and structural changes characterising diabetic nephropathy. These four pathways are the polyol pathway, non-enzymatic glycation, glucose autoxidation and de novo synthesis of diacylglycerol leading to protein kinase C and phospholipase A2 activation.

Screening for large bowel neoplasms in individuals with a family history of colorectal cancer.

Logistical problems associated with population screening for colorectal cancer are identified and the possibility of targeting screening to those with a familial predisposition to the disease is discussed. Evidence for a substantial genetic effect on the overall incidence of colorectal cancer is reviewed. The screening detection rate of colorectal neoplasms in relatives of patients with colorectal cancer has been shown to be higher than that expected in a non-selected population; the evidence that polypectomy will reduce future colorectal cancer risk in such individuals is explored.

Colorectal cancer genetics.

Due to the accessibility of the intermediate steps in the progression of colorectal cancer and to the existence of heritable susceptibility to the disease, molecular genetic analysis of colorectal carcinogenesis seems likely to answer many of the questions concerning the fundamental nature of the common human epithelial cancers. Several genetic events appear to be required and, although there is no stringent adherence to any particular sequence of events, the accumulation of genetic defects does show some loose order. Each event must confer growth advantage in order to allow further clonal expansion.

Activation of phospholipase D by glyceraldehyde in isolated islet cells follows protein kinase C activation.

Our recent studies have demonstrated the presence in neonatal islet cells and intact adult islets of a phosphatidylcholine-directed phospholipase D (PLD) which is activated after phorbol ester stimulation. The present study describes PLD activation in the presence of a carbohydrate insulin secretagogue. At the highest concentration tested (20 mM) the triose, glyceraldehyde, induced formation of phosphatidic acid in cells prelabeled with [14C]arachidonic acid or [3H]myristic acid (164 +/- 7 and 210 +/- 9% of basal phosphatidic acid values, respectively).

A candidate spermatogenesis gene on the mouse Y chromosome is homologous to ubiquitin-activating enzyme E1.

The human X-linked gene A1S9 complements a temperature-sensitive cell-cycle mutation in mouse L cells, and encodes the ubiquitin-activating enzyme E1. The gene has been reported to escape X-chromosome inactivation, but there is some conflicting evidence. We have isolated part of the mouse A1s9 gene, mapped it to the proximal portion of the X chromosome and shown that it undergoes normal X-inactivation.

MCC, a candidate familial polyposis gene in 5q.21, shows frequent allele loss in colorectal and lung cancer.

MCC is a gene located within human chromosome band 5q.21 that shows somatically acquired mutations in colorectal cancer, and may be identical to the gene responsible for inheritance of familial adenomatous polyposis. Here we demonstrate that alleles contiguous with or within MCC are deleted in a high proportion of sporadic colorectal carcinomas.

The effect of aldose reductase inhibitors on glomerular prostaglandin production and urinary albumin excretion in experimental diabetes mellitus.

The effect of two structurally unrelated aldose reductase inhibitors, sorbinil and ponalrestat, on glomerular prostaglandin production and urinary albumin excretion was investigated in rats with diabetes induced by streptozotocin. It was found that both aldose reductase inhibitors, when administered from the time of induction of the diabetes, significantly decreased the raised urinary albumin excretion in the diabetic rats, although it remained elevated compared with non-diabetic rats. Glomerular prostaglandin E and 6-keto-prostaglandin F1 alpha production was significantly increased in glomeruli obtained from the diabetic rats.

Modulation of phospholipase A2 activity by epidermal growth factor (EGF) in CHO cells transfected with human EGF receptor. Role of receptor cytoplasmic subdomain.

Activation of phospholipase A2 (PLA2) in response to external stimuli may play a pivotal role in signal-transduction pathways via the generation of important cellular intermediates, including prostaglandins. Epidermal growth factor (EGF) has been shown to modulate prostaglandin production, possibly via direct activation of PLA2 or indirectly via interaction with a PLA2-modifying protein such as lipocortin I. We have investigated these pathways with two CHO cell-lines, one (CHOwt) transfected with the full-length human EGF receptor and the second (CHO 11) with a deletion mutant, delta 990, that has lost the autophosphorylation sites and part of the internalization domain.

Linked DNA markers for presymptomatic diagnosis of familial adenomatous polyposis.

41 symptom-free individuals aged 0-39 years who were at risk of familial adenomatous polyposis (FAP) were genotyped with six linked DNA probes. 28 individuals were informative for probes flanking the gene and 14 people assigned a probe-derived risk of over 0.93 were subsequently shown to be affected by clinical screening.