Fimbriae, transmembrane signaling, and cell activation.
Explore the source record for details and available documents.
Ceramides↗
Biomedical subjects
M Svensson
Publications and source records attributed to M Svensson.
Carbohydrate receptor depletion as an antimicrobial strategy for prevention of urinary tract infection.
Explore the source record for details and available documents.
1-Deoxynojirimycin↗
Salmonella typhimurium-induced cytokine production and surface molecule expression by murine macrophages.
The influence of Salmonella enterica serovar Typhimurium (S. typhimurium) on co-stimulatory molecule expression, cytokine production and induction of nitric oxide synthase (iNOS) by murine macrophages (Mphi), as well as the influence of the phoP locus on these aspects of S. typhimurium-Mphi interaction, was characterized. Pulsing Mphi with S. typhimurium resulted in increased surface expression of MHC-I, MHC-II, CD86 and CD54. Furthermore, co-incubating S. typhimurium with Mphi resulted in interleukin (IL)-12p40, IL-6 and tumor necrosis factor-alpha production as well as iNOS induction while IL-12p70 was not detectable. Finally, although phoP did not influence the level of surface molecule expression or cytokine production by S. typhimurium-pulsed Mphi phoP did influence the level of iNOS induction. Together these data show that S. typhimurium interaction with Mphi activates these cells in ways that may enhance their ability to productively stimulate Salmonella-specific T cells following phagocytic processing and presentation of Salmonella antigens.
Animals↗
Spin and fluorescent probing of the binding interface between tissue factor and factor VIIa at multiple sites.
The specific complex between the extracellular part of tissue factor (sTF) and factor VIIa (FVIIa) was chosen as a model for studies of the binding interface between two interacting proteins. Six surface-exposed positions in sTF, residues known to contribute to the sTF-FVIIa interaction, were selected for cysteine mutation and site-directed labeling with spin and fluorescent probes. The binding interface was characterized by spectral data from electron paramagnetic resonance (EPR) and steady-state and time-domain fluorescence spectroscopy. The labels reported on compact local environments at positions 158 and 207 in the interface region between sTF and the gamma-carboxyglutamic acid (Gla) domain of FVIIa, and at positions 22 and 140 in the interface region between sTF and the first epidermal growth factor-like (EGF1) domain of FVIIa. The tightness of the local interactions in these parts of the interface is similar to that seen in the interior of globular proteins. This was further emphasized by the reduced local polarity detected by the fluorescent label upon FVIIa binding, especially in the sTF-Gla region. There were indications of structural rigidity also at positions 45 and 94 in the interface region between sTF and the protease domain (PD) of FVIIa, despite the perturbed cofactor function of these sTF variants. The results of the present study indicate that the multi-probing approach enables comparison of the tightness and characteristics of interaction along the binding interface of a protein complex. This approach also increases the probability of acquiring reliable structural data that are descriptive of the wild-type proteins.
Amino Acid Substitution↗
Pyrone and pyridone compounds in the liquid culture of Physisporinus sanguinolentus.
Chromatographic separation of the liquid culture filtrate of the basidiomycete fungus Physisporinus sanguinolentus has yielded three new compounds viz., 2-methyl-4-pyrone, 2-methyl-5,6-dihydro-4-pyrone and the pyridone form of 4-hydroxy-2-methylpyridine, together with the known triacetic acid lactone, the sesquiterpene dialdehyde merulidial and a derivative of merulidial. Their structures were elucidated by spectroscopic analysis and by comparison to literature data and a synthetic sample. One of the compounds, merulidial, was shown to inhibit the germination of spores and the hyphal growth of the wood-rotting basidiomycete Heterobasidion annosum and the saprophytic mould Cladosporium cucumerinum.
Chromatography, High Pressure Liquid↗
Chromatographic retention of drug molecules on immobilised liposomes prepared from egg phospholipids and from chemically pure phospholipids.
The partitioning of a chemically diverse set of drugs into liposomes was studied by immobilised liposome chromatography (ILC). For this purpose liposomes composed of (i) purified egg phospholipids (EPL), (ii) synthetic phosphatidylcholine (PC), (iii) PC--synthetic phosphatidylethanolamine (PE) 80:20 (mol/mol) and (iv) PC--synthetic phosphatidylserine (PS) 80:20 (mol/mol) were immobilised in gel beads by freeze-thawing. The drug partitioning was assessed from the retention volume, which was expressed as a capacity factor, K(s), normalised with respect to the amount of immobilised phospholipid. The drug retention on EPL, PC and PC--PE liposomes was very similar, whereas the negatively charged PC--PS liposomes increased the retention of positively charged and decreased retention of negatively charged drugs. The partitioning of drugs on liposome columns (log K(s)) versus their octanol--water partitioning (log P(oct)) showed three separate rectilinear relationships, depending on the charge of the compound (neutral, positive, or negative). Statistical analysis (ANCOVA) proved that the lines had similar slopes. Repeated analysis of four reference compounds showed a low variation (<0.12 log units) over time (about 250 days). A close relationship was observed between the drug retention in short EPL columns with a low content of phospholipids and the retention in longer standard EPL columns. The short 'quick screen bilayer columns' permit analysis of highly lipophilic compounds within 30 min and are thus applicable for medium-throughput screening in drug discovery settings. A very strong rectilinear relationship (r(2)=0.95, n=13) between log K(s) (EPL) and published liposome partitioning data (log D(mem)) confirmed that the ILC drug retention reflects the drug partitioning into the lipid bilayers. A moderate to fair rectilinear relationship was observed between the normalised retention on PC, PC-PE and EPL liposomes (r(2)=0.79, 0.86 and 0.85, respectively, n=24) and corresponding published log k'(IAM) data obtained on immobilised artificial membrane (IAM) columns. Transport across Caco-2 cell monolayers (log P(c)) showed curvilinear relationships with log K(s), log k'(IAM), log P(oct) and log D(oct). The drug fraction absorbed in humans showed a similar relationship to log K(s) values as to surface plasmon resonance signals representing drug-liposome interaction (Danelian et al., 2000 J Med Chem, 43, 2083--2086).
Adrenergic beta-Antagonists↗
A prospective study of obesity and cancer risk (Sweden).
OBJECTIVE: [corrected] We evaluated the relation between obesity and the risks for various forms of cancer. METHODS: In a population-based cohort of 28,129 hospital patients (8165 men, 19,964 women) with any discharge diagnosis of obesity (9557 only diagnosis, 5266 primary, 13,306 secondary) during 1965-1993, cancer incidence was ascertained through 1993 by record linkage to the nationwide Swedish Cancer Registry. Cancer risk was estimated using the standardized incidence ratio (SIR, with 95% confidence interval), which is the ratio of the observed number of cancers to that expected. RESULTS: Overall, a 33% excess incidence of cancer was seen in obese persons, 25% in men and 37% in women. Significant risk elevations were observed for cancers of the small intestine (SIR = 2.8; 95% CI 1.6-4.5), colon (1.3; 1.1-1.5), gallbladder (1.6; 1.1-2.3), pancreas (1.5; 1.1-1.9), larynx (2.1; 1.1-3.5), renal parenchyma (2.3; 1.8-2.8), bladder (1.2; 1.0-1.6), cervix uteri (1.4; 1.1-1.9), endometrium (2.9; 2.5-3.4), ovary (1.2; 1.1-1.5), brain (1.5; 1.2-1.9), and connective tissue (1.9; 1.1-3.0), and for lymphomas (1.4; 1.0-1.7), with higher risk observed for Hodgkin's disease only in men (3.3; 1.4-6.5) and for non-Hodgkin's lymphoma only in women (1.6; 1.2-2.1). The association of obesity with risk of breast, prostate and pancreas cancers was modified by age. CONCLUSIONS: Obesity is associated with more forms of cancer than previously reported.
Adolescent↗
A model for peak and width of signaling windows: Ips duplicatus and Chilo partellus pheromone component proportions--does response have a wider window than production?
Pheromone communication systems have a reliable signal with a restricted window of amounts and ratios released and perceived. We propose a model based on a Gaussian response profile that allows a quantification of the response peak (location of optimum) and a measure of the peak width (response window). Interpreting the Gaussian curve, fitted by nonlinear regression (NLR), as a standard normal distribution, the peak location equals the mean (it) and the window width equals 2 x the standard deviation (2sigma). The NLR procedure can provide an objective measure for both peak location and width for a wide range of data sets. Four empirical data sets as well as 10 literature data sets were analyzed. The double-spined spruce engraver, Ips duplicatus, was field tested in four populations to find the optimum proportion for attraction to the two male aggregation pheromone components, ipsdienol (Id) and (E)-myrcenol(EM), ranging from 0 to 100% of Id. Tests in Norway and the Czech Republic confirmed the preference of western populations for a blend between 50 and 90% Id. A population in Inner Mongolia showed a preference for traps with the 10 and 50% Id baits. The NLR fitted values for response peak and width (mu; 2sigma) were: Norway 0.64, 0.73; Czech Republic 0.53, 0.73; NE China 0.77, 0.29; and Inner Mongolia 0.33, 0.50. The signal produced by Norwegian field-collected males had a narrower window width (2sigma = 0.12). Males of the maize stem borer, Chilo partellus, were tested in a flight tunnel for their response to variation in the two major female sex pheromone gland components, (Z)- l1-hexadecenal and the corresponding alcohol (OH). Variation of the alcohol in seven levels from 2 to 29% OH showed the highest male response for 17% OH. For all behavioral steps, the peak of male response was near mu = 0.14, while the window width fell from 2sigma = 0.5 to 0.2 for eight sequential behavioral steps from take-off to copulation. Female production had a similar peak location (mu = 0.13) but a narrower width, 2sigma = 0.14. Literature data from other moth species showed similar patterns, with a wider male response relative to the female production windows. Literature data on response to enantiomer ratios in a hymenopteran and to pheromone amounts in a dipteran were also described by our model. In a bark beetle population (Ips pini), with two hybridizing enantiomeric strains, the production peaks were narrower (0.1) than the response peaks (0.5). Thus, it in general, seems that in the pheromone systems analyzed, the width of the response window (2sigma = 0.1 to 0.8) is larger than that of the production window (2sigma = 0.03 to 0.14), irrespective of the sex of the sender.
Animals↗
Selection of uremic patients for kidney transplantation.
Selection of patients for kidney transplantations is necessary due to the shortage of organs. The process has not been greatly studied. Twelve hypothetical cases were constructed, each with one or several relative contraindications, such as cardiovascular disease, diabetes, old age or a mental disorder. The cases were submitted to 40 nephrologists, chosen to represent the recruitment areas of the four Swedish transplant units. They were asked to declare whether the 'patient' was suitable for transplantation or not, and, independently, whether the patient would be referred to the transplant unit. The same cases were evaluated by 3-4 representatives of each transplant unit. The response rate was 100%. A median of 6 cases was considered suitable (range 3-11). The acceptance rate differed significantly between the four unit areas, from 4 cases (3-7) to 7 (4-11), p=0.014. Nephrologists would accept fewer patients than staff from the transplant units, 5 (3-10) vs. 7 (3-11), p=0.009. Most of the latter difference was compensated for by referral of borderline cases to the unit. Only 5 individual cases were equally judged by at least 75% of the respondents. Discrepancies in view were noted with respect to the significance of old or young age, the patient's determination and severe obesity.
Adult↗
Descending aortic blood flow and cardiac output: a clinical and experimental study of continuous oesophageal echo-Doppler flowmetry.
BACKGROUND: Several studies have demonstrated that perioperative optimisation of oxygen delivery and haemodynamics can reduce mortality and morbidity for high-risk surgical patients. To optimise cardiac output, reliable, continuous and "less invasive" methods for measuring cardiac output are urgently needed. METHODS: Eight landrace pigs were studied during experimental repeated cardiac tamponade and 14 patients during liver transplantation. Aortic blood flow was measured by using transoesophageal echo-Doppler technique. A total of 91 paired measurements of aortic blood flow and cardiac output with different techniques were performed in the pigs and 124 paired measurements in the patients. RESULTS: Transoesophageal echo-Doppler did provide continuous real-time monitoring of the rapid and dramatic haemodynamic changes occurring during cardiac tamponade and during liver transplantation, while only intermittent information was obtained from the bolus thermodilution technique. Changes in haemodynamics were more difficult to detect with the "continual" cardiac output thermodilution technique. Changes in aortic blood flow closely followed changes in cardiac output determined by the bolus thermodilution technique both in pigs (r= 0.89) and in patients (r=0.80). In patients, aortic blood flow constituted about 70% of cardiac output determined by the bolus thermodilution technique. CONCLUSIONS: A combined echo-Doppler technique can be valuable for continuous monitoring of haemodynamic changes in the perioperative setting, and changes in aortic blood flow agree well with corresponding changes in cardiac output intermittently obtained by thermodilution cardiac output measurements. With the combined echo-Doppler technique a proper position of the Doppler beam is greatly facilitated by the M-mode echo visualisation of the aortic wall and aortic cross-sectional area is continuously measured.
Adult↗
Escherichia coli P fimbriae utilize the Toll-like receptor 4 pathway for cell activation.
Fimbriae mediate bacterial attachment to host cells and provide a mechanism for tissue attack. They activate a host response by delivery of microbial products such as lipopolysaccharide (LPS) or through direct fimbriae-dependent signalling mechanisms. By coupling to glycosphingolipid (GSL) receptors, P fimbriae trigger cytokine responses in CD14 negative host cells. Here we show that P fimbriae utilize the Toll-like receptor 4 (TLR4)-dependent pathway to trigger mucosal inflammation. Escherichia coli strains expressing P fimbriae as their only virulence factor stimulated chemokine and neutrophil responses in the urinary tract of TLR4 proficient mice, but TLR4 defective mice failed to respond to infection. Mucosal cells were CD14 negative but expressed several TLR species including TLR4, and TLR4 protein was detected. Infection with P fimbriated bacteria stimulated an increase in TLR4 mRNA levels. The activation signal did not involve the LPS-CD14 pathway and was independent of lipid A myristoylation, as shown by mutational inactivation of the msbB gene. Co-staining experiments revealed that TLR4 and the GSL receptors for P fimbriae co-localized in the cell membrane. The results demonstrate that P fimbriae activate epithelial cells by means of a TLR4-dependent signalling pathway, and suggest that GSL receptors for P fimbriae can recruit TLR4 as co-receptors.
Animals↗
Complement activation in the human brain after traumatic head injury.
The complement cascade has been suggested to be involved in the development of secondary brain injuries following brain contusions, based on animal experiments. The aim of the present study was to examine the possible involvement of the complement cascade following traumatic head injury in the human brain. Sixteen patients were included in this study, 12-77 years of age, treated at the neurointensive care unit for traumatic brain contusions. All of these patients were operated with frontal or temporal lobe resection due to intractable intracranial hypertension. The resected tissue was analyzed with regard to components related to complement activation. The time interval between accident and operation was 2-82 h. Brain tissue from three patients operated with hippocampectomy due to epilepsy, including temporal lobe resection, were used as controls. We found increased immunoreactivity for complement components C1q, C3b, and C3d and the membrane attack complex (MAC), C5b-9, in the immediate vicinity of neurons in the penumbra area of the contusion. These findings constitute histological evidence for activation of the complement cascade in the penumbra of cortical contusions in the human brain. Using in situ hybridization, we also found C3-mRNA in the penumbra, suggesting a local synthesis of complement. Furthermore, upregulation of the endogenous complement regulator clusterin was found in some neurons in the same area. We suggest that unknown compounds in the debris from injured neurons or myelin breakdown products trigger complement activation, including formation of C5b-9. Activated complement components may stimulate accumulation of inflammatory cells and formation of brain edema, as well as having membrane destructive effects by the end product MAC, thereby being mediators in the development of secondary brain damage.
Adolescent↗
In vivo activation of dendritic cells and T cells during Salmonella enterica serovar Typhimurium infection.
The present study was initiated to gain insight into the interaction between splenic dendritic cells (DC) and Salmonella enterica serovar Typhimurium in vivo. Splenic phagocytic cell populations associated with green fluorescent protein (GFP)-expressing bacteria and the bacterium-specific T-cell response were evaluated in mice given S. enterica serovar Typhimurium expressing GFP and ovalbumin. Flow cytometry analysis revealed that GFP-positive splenic DC (CD11c+ major histocompatibility complex class II-positive [MHC-II+] cells) were present following bacterial administration, and confocal microscopy showed that GFP-expressing bacteria were contained within CD11c+ MHC-II+ splenocytes. Furthermore, splenic DC and T cells were activated following Salmonella infection. This was shown by increased surface expression of CD86 and CD40 on CD11c+ MHC-II+ cells and increased CD44 and CD69 expression on CD4+ and CD8+ T cells. Salmonella-specific gamma interferon (IFN-gamma)-producing cells in both of these T-cell subsets, as well as cytolytic effector cells, were also generated in mice given live bacteria. The frequency of Salmonella-specific CD4+ T cells producing IFN-gamma was greater than that of specific CD8+ T cells producing IFN-gamma in the same infected animal. This supports the argument that the predominant source of IFN-gamma production by cells of the specific immune response is CD4+ T cells. Finally, DC that phagocytosed live or heat-killed Salmonella in vitro primed bacterium-specific IFN-gamma-producing CD4+ and CD8+ T cells as well as cytolytic effector cells following administration into naïve mice. Together these data suggest that DC are involved in priming naïve T cells to Salmonella in vivo.
Animals↗
Hexarelin--evaluation of factors influencing oral bioavailability and ways to improve absorption.
Hexarelin, a hexapeptide with growth hormone-releasing activity, has been found in man to have a biological bioavailability (estimated from growth hormone levels) of 0.3+/-0.1% after oral administration. The cause of the low oral efficacy of hexarelin and means of improving its absorption have been evaluated. It was found that hexarelin was degraded in the presence of the contents of the intestine. The metabolite was identified as hexarelin deamidated at the lysine residue. The degradation of hexarelin in the contents of rat ileum was inhibited by the addition of chymostatin, Pefabloc SC, EDTA, and EGTA. Furthermore, the presence of pancreatic proteases from pancrease substitute drugs caused a degradation of hexarelin that could be inhibited by the addition of Pefabloc SC. The same hexarelin metabolite that was found with the contents of rat ileum was found in the presence of human, porcine and bovine trypsin. Hexarelin permeability across rat ileum and in Caco-2 cell monolayers was low. An increase in hexarelin permeability was observed in the presence of different permeability enhancing agents.
Administration, Oral↗
The 'innate' host response protects and damages the infected urinary tract.
Symptoms of infection and tissue pathology are caused by the host response; not by the microbe per se. The same response is also critical for the defence and is needed to clear infection. It is therefore essential to understand how the host response is activated and to identify the critical effector mechanisms of the defence. We have studied these issues in the urinary tract infection (UTI) model. The symptoms of UTI and the host defence both rely on the so-called 'innate' immune system, making this one of the best characterized human disease models of 'innate immunity. We discuss the critical molecular events that determine whether the host response will be activated by P-fimbriated uropathogenic Escherichia coli as well as factors determining whether the patient develops acute pyelonephritis or asymptomatic bacteriuria. We will describe the glycoconjugate receptors used by the P-fimbriated bacteria adhering to host tissues, the recruitment of TLR4 co-receptors and the signalling pathways that allow progression to symptomatic disease, and discuss how these mechanisms are altered in asymptomatic carriers, presenting the possible genetic basis for unresponsiveness. We have shown that neutrophils are the critical effectors of the host defence and that neutrophil dysfunctions lead to acute pyelonephritis and renal scarring. Here we discuss the mechanisms of neutrophil-mediated, chemokine receptor (CXCR1)-dependent clearance, and the defect in interleukin-8 receptor homolog knock-out (IL-8Rh KO) mice and describe the data linking low CXCR1 expression to recurrent pyelonephritis in man, as well as the information on the genetic basis for low CXCR1 expression in affected patients. Finally, the mechanisms of renal scarring in IL8Rh KO mice will be discussed in relation to human disease. Our studies hold the promise to provide a molecular and genetic explanation for disease susceptibility in some patients with UTI and to offer more precise tools for the diagnosis and therapy of these infections.
Animals↗
Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress.
The influence of endurance training on oxidative phosphorylation and the susceptibility of mitochondrial oxidative function to reactive oxygen species (ROS) was investigated in skeletal muscle of four men and four women. Mitochondria were isolated from muscle biopsies taken before and after 6 weeks of endurance training. Mitochondrial respiration was measured before and after exposure of mitochondria to exogenous ROS (H2O2 + FeCl2). Endurance training increased peak pulmonary O2 uptake (VO2,peak) by 24 % and maximal ADP-stimulated mitochondrial oxygen consumption (state 3) by 40% (P<0.05). Respiration in the absence of ADP (state 4), the respiratory control ratio (RCR = state 3/state 4) and the ratio between added ADP and consumed oxygen (P/O) remained unchanged by the training programme. Exposure to ROS reduced state 3 respiration but the effect was not significantly different between pre- and post-training samples. State 4 oxygen consumption increased after exposure to ROS both before (+189 %, P< 0.05) and after training (+243 %, P<0.05) and the effect was significantly higher after training (P<0.05, pre- vs. post-training). The augmented state 4 respiration could in part be attenuated by atractyloside, which indicates that ADP/ATP translocase was affected by ROS. The P/O ratio in ROS-treated mitochondria was significantly lower (P<0.05) compared to control conditions, both before (-18.6+/-2.2 %) and after training (-18.5+/-1.1%). Muscle activities of superoxide dismutase (mitochondrial and cytosolic), glutathione peroxidase and muscle glutathione status were unaffected by training. There was a positive correlation between muscle superoxide dismutase activity and age (r = 0.75; P<0.05; range of age 20-37 years), which may reflect an adaptation to increased generation of ROS in senescent muscle. The muscle glutathione pool was more reduced in subjects with high activity of glutathione peroxidase (r = 0.81; P<0.05). The influence of short-term training on mitochondrial oxygen consumption has for the first time been investigated in human skeletal muscle. The results showed that maximal mitochondrial oxidative power is increased after endurance training but that the efficiency of energy transfer (P/O ratio) remained unchanged. Antioxidative defence was unchanged after training when expressed relative to muscle weight. Although this corresponds to a reduced antioxidant protection per individual mitochondrion, the sensitivity of aerobic energy transfer to ROS was unchanged. However, the augmented ROS-induced non-coupled respiration after training indicates an increased susceptibility of mitochondrial membrane proton conductance to oxidative stress.
Adult↗
Skin and hair follicle integrity is crucially dependent on beta 1 integrin expression on keratinocytes.
beta 1 integrins are ubiquitously expressed receptors that mediate cell-cell and cell-extracellular matrix interactions. To analyze the function of beta1 integrin in skin we generated mice with a keratinocyte-restricted deletion of the beta 1 integrin gene using the cre-loxP system. Mutant mice developed severe hair loss due to a reduced proliferation of hair matrix cells and severe hair follicle abnormalities. Eventually, the malformed hair follicles were removed by infiltrating macrophages. The epidermis of the back skin became hyperthickened, the basal keratinocytes showed reduced expression of alpha 6 beta 4 integrin, and the number of hemidesmosomes decreased. Basement membrane components were atypically deposited and, at least in the case of laminin-5, improperly processed, leading to disruption of the basement membrane and blister formation at the dermal-epidermal junction. In contrast, the integrity of the basement membrane surrounding the beta 1-deficient hair follicle was not affected. Finally, the dermis became fibrotic. These results demonstrate an important role of beta 1 integrins in hair follicle morphogenesis, in the processing of basement membrane components, in the maintenance of some, but not all basement membranes, in keratinocyte differentiation and proliferation, and in the formation and/or maintenance of hemidesmosomes.
Animals↗
Conversion of alpha-lactalbumin to a protein inducing apoptosis.
In this study alpha-lactalbumin was converted from the regular, native state to a folding variant with altered biological function. The folding variant was shown to induce apoptosis in tumor cells and immature cells, but healthy cells were resistant to this effect. Conversion to HAMLET (human alpha-lactalbumin made lethal to tumor cells) required partial unfolding of the protein and a specific fatty acid, C18:1, as a necessary cofactor. Conversion was achieved with alpha-lactalbumin derived from human milk whey and with recombinant protein expressed in Escherichia coli. We thus have identified the folding change and the fatty acid as two key elements that define HAMLET, the apoptosis-inducing functional state of alpha-lactalbumin. Although the environment in the mammary gland favors the native conformation of alpha-lactalbumin that serves as a specifier in the lactose synthase complex, the conditions under which HAMLET was formed resemble those in the stomach of the nursing child. Low pH is known to release Ca(2+) from the high-affinity Ca(2+)-binding site and to activate lipases that hydrolyze free fatty acids from milk triglycerides. We propose that this single amino acid polypeptide chain may perform vastly different biological functions depending on its folding state and the in vivo environment. It may be speculated that molecules like HAMLET can aid in lowering the incidence of cancer in breast-fed children by purging of tumor cells from the gut of the neonate.
Apoptosis↗