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1.
Nihon Koshu Eisei Zasshi ; 48(12): 938-48, 2001 Dec.
Article in Japanese | MEDLINE | ID: mdl-11831022

ABSTRACT

OBJECTS: In this study, we examine the relationship between job satisfaction(JS) and life satisfaction(LS) and the moderating effect of coping with JS and LS correlation (spillover) in order to obtain information of Human Resources Management for care workers in Health-Social service facilities. METHODS: Questionnaires were sent to individuals working in geriatric care facilities and responses were returned from a total of 612 females aged 20 to 63. Subjects were classified into 3 groups according to their age. Relationships between JS and LS were examined by multiple regression analysis and the moderating effect of coping behavior on spillover was examined by comparison of correlation coefficients of spillovers between the high score group and low score groups based on scores for coping behavior. RESULTS: Several significant causal interrelations were seen between JS and LS such as JS of "work time and shift" and LS of "health", but a moderating effect of coping with spillover was seen only in the middle age group (35-49). CONCLUSION: The results showed the need in some way to consider non-work life besides work life in the actual personnel programs of Health-Social service facilities, and indicated that relationships between coping and spillover depend on the age.


Subject(s)
Adaptation, Psychological , Health Services for the Aged , Homes for the Aged , Job Satisfaction , Personal Satisfaction , Adult , Aged , Female , Humans , Japan , Middle Aged , Surveys and Questionnaires , Workforce
2.
J Submicrosc Cytol Pathol ; 31(2): 215-9, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10457607

ABSTRACT

In infant mice (2 weeks old) fed a diet with excess iron for one week, numerous huge iron particles around micro blood vessels under the basement membrane of intestinal epithelial cells were observed by electron microscopy. The frequency of occurrence of these particles (0.24 +/- 0.04 micron diameter) was markedly higher in mice fed a casein-based diet than in mice fed an amino acid-based diet. The quantity of these particles in both groups decreased in proportion to the term of 2 or 3 weeks. Changes in morphological features, such as opening of the intercellular junctions between intestinal epithelial cells, were also observed in these experimental groups. On the other hand, in mice fed the casein-based diet with excess iron, fat globules appeared in the intestinal epithelial tissue (intestinal epithelial cells, interstitial tissue, lympha) and the occurrence of these increased gradually in proportion to the term of feeding. These fat globules were not observed in mice fed the amino acid-based diet with excess iron. These phenomena might be elicited temporally in infant mice fed excess iron together with protein. The mechanisms of fat globule formation remain unclear.


Subject(s)
Epithelial Cells/chemistry , Intestines/blood supply , Iron/analysis , Amino Acids/administration & dosage , Animals , Animals, Newborn , Blood Vessels/chemistry , Caseins/administration & dosage , Dietary Proteins/administration & dosage , Electron Probe Microanalysis , Epithelial Cells/ultrastructure , Female , Iron/administration & dosage , Mice , Mice, Inbred BALB C , Microcirculation/chemistry , Microscopy, Electron , Time Factors
3.
Adv Exp Med Biol ; 443: 239-46, 1998.
Article in English | MEDLINE | ID: mdl-9781364

ABSTRACT

Recently we have reported that orally administered bovine Lf(bLf) exerts bacteriostatic effects against bacterial overgrowth in the intestine of specific-pathogen-free (SPF) mice fed milk. In this animal model, the in vivo bacteriostatic effect of bLf against the proliferation of intestinal Enterobacteriaceae, the bacteria most sensitive to bLf, was independent of the iron-chelating ability of bLf. In addition various proteolytic hydrolysates of bLf (with differing antibacterial activities in vitro) showed the same bacteriostatic effect as undigested bLf. These results suggest that the mechanism of in vivo bacteriostasis of Lf differs from the in vitro mechanism reported. In SPF mice fed milk differing in concentrations of lactose, glucose and galactose, the proliferation of intestinal Enterobacteriaceae was dependent on the carbohydrate concentration in the diet. The addition of 2% bLf to the diets significantly suppressed this carbohydrate-dependent proliferation of bacteria except in the case of diets containing excess carbohydrate. In germ-free mice fed sterile milk, the addition of 2% bLf to milk resulted in a significant decrease in concentrations of lactose, glucose and galactose in the cecal contents. In an in vitro assay system using everted sacs of the small intestine of SPF mice, both bLf and its pepsin hydrolysate apparently stimulated glucose absorption. Based on these findings, we propose that the in vivo mechanism of action of ingested bLf involves the stimulation of carbohydrate absorption resulting in a bacteriostatic effect against Enterobacteriaceae in the intestine of mice fed milk.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Enterobacteriaceae Infections/drug therapy , Enterobacteriaceae/drug effects , Lactoferrin/therapeutic use , Animals , Anti-Bacterial Agents/pharmacology , Carbohydrate Metabolism , Cattle , Enterobacteriaceae Infections/metabolism , Lactoferrin/pharmacology , Mice , Mice, Inbred BALB C
4.
Cell Immunol ; 187(1): 34-7, 1998 Jul 10.
Article in English | MEDLINE | ID: mdl-9682001

ABSTRACT

Bovine LF (bLF) at concentrations in the range of 50-250 micrograms/ml enhanced the phagocytic activity of human neutrophils as determined by measuring the incorporation of FITC-labeled latex beads by flow cytometry. The stimulatory effect of bLF was not abrogated by hydrolysis with pepsin. Bovine lactoferricin (bLFcin), which is a bactericidal fragment purified from a pepsin hydrolysate of bLF (bLFH), also enhanced the phagocytic activity, whereas, in contrast, the fraction of bLFH depleted of bLFcin showed no stimulatory effect. The phagocytosis-enhancing activity of bLF still remained after washing the neutrophils, following exposure to bLF. Also, bLF pretreatment of the latex beads stimulated their uptake. These results demonstrate that bLF is effective in promoting the phagocytic activity of human neutrophils. This activity appears to be due to its bLFcin domain and may involve dual mechanisms of direct binding to neutrophils and opsonin-like activity.


Subject(s)
Lactoferrin/pharmacology , Neutrophils/drug effects , Neutrophils/immunology , Phagocytosis/drug effects , Animals , Bacteria/immunology , Bacteria/metabolism , Binding Sites , Cattle , Humans , In Vitro Techniques , Lactoferrin/analogs & derivatives , Lactoferrin/chemistry , Lactoferrin/metabolism , Neutrophils/metabolism , Peptide Fragments/chemistry , Peptide Fragments/metabolism , Peptide Fragments/pharmacology
5.
J Submicrosc Cytol Pathol ; 30(2): 279-83, 1998 Apr.
Article in English | MEDLINE | ID: mdl-9648291

ABSTRACT

The changes in fine structure of the intestinal tract in young adult (4 week-old) and infant (2 week-old) mice fed a diet containing different amounts of iron salt (Fe-0, Fe-2.5, Fe-25: 0, 2.5 and 25 mg Fe/100 g diet, respectively) for a long-term (1 or 2 weeks) were investigated. The hepatic iron levels in infant mice fed Fe-25 for 2 weeks were significantly higher than those observed after 1 week of feeding, but there was no such increase in young adult mice during the feeding period. Observations of fine structure indicated typical signs of impairment of enterocytes due to excess iron such as the opening of intercellular junctions between adjacent epithelial cells and the marked appearance of eosinophilic leukocytes outside the basement membrane in young adult and infant mice fed Fe-25. The frequency of the opening in intercellular junctions increased in young adult mice fed Fe-25 for 2 weeks, but decreased in infant mice. On the contrary, under iron-deficient conditions, the frequency in infant mice was higher than that in young adult mice. The appearance of eosinophilic leukocytes indicated that some immunological reaction was elicited in both groups of mice fed Fe-25 for 2 weeks.


Subject(s)
Intestines/ultrastructure , Iron, Dietary/metabolism , Animal Feed , Animals , Body Weight , Female , Hematocrit , Hemoglobins/metabolism , Intestinal Absorption , Intestines/pathology , Iron/metabolism , Liver/metabolism , Liver/pathology , Mice , Mice, Inbred BALB C , Time Factors
6.
Pigment Cell Res ; 11(1): 12-7, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9523330

ABSTRACT

We assessed the effects of arbutin on the pigmentation of cultured normal human melanocytes. As indicated by a cell-blotting assay, arbutin at concentrations in the range of 0.5-8 mM increased the pigmentation of the cultured melanocytes, while kojic acid at concentrations in the range of 0.5-4 mM decreased the pigmentation. The pigmentation-augmenting effect of arbutin was further confirmed by the results of a cell-pelleting assay, the traditional method of assessment. Treatment of the cells with arbutin increased the melanin content of the cells and the protein content as well. On the other hand, the tyrosinase activity in the cells was reduced by arbutin treatment. The levels of transcription of tyrosinase and tyrosinase related protein-1 genes were not affected by arbutin treatment as indicated by a semi-quantitative reverse transcription-polymerase chain reaction assay. These results demonstrate that arbutin promotes an increase in pigmentation of cultured human melanocytes that is not mediated by augmented tyrosinase activity.


Subject(s)
Arbutin/pharmacology , Melanocytes/physiology , Membrane Glycoproteins , Monophenol Monooxygenase/metabolism , Oxidoreductases , Pigmentation/drug effects , Cell Division/drug effects , Cells, Cultured , Dose-Response Relationship, Drug , Humans , Infant, Newborn , Melanins/metabolism , Melanocytes/cytology , Melanocytes/drug effects , Monophenol Monooxygenase/drug effects , Monophenol Monooxygenase/genetics , Proteins/drug effects , Proteins/genetics , Pyrones/pharmacology
7.
Mech Ageing Dev ; 100(1): 67-76, 1998 Jan 12.
Article in English | MEDLINE | ID: mdl-9509396

ABSTRACT

Brown adipose tissue (BAT), a highly thermogenic tissue in young animals, is relatively atrophied and thermogenetically quiescent (e.g. as measured by colonic temperature) in mice that are obese or old. The aim of the current study was to investigate the effect of aging (3.1 (young) versus 14.6 (old) months old) on BAT activity in lean and obese (ob/ob) mice. In young but not in old mice, BAT mass in terms of weight per unit body weight was significantly lower in obese mice than in lean mice. A significant increase in BAT mass of obese mice with age was noted in terms of weight or weight per unit body weight, probably because of a tendency to become white adipose tissue and the deposit of fat, accompanied by the lowest levels of total protein, guanosine 5'-diphosphate binding, and uncoupling protein (UCP) antigen in the mitochondria of BAT, as well as the lowest colonic temperature among the groups examined. Unlike old lean animals, the old obese (ob/ob) animals did not increase but rather decreased the expression of mRNA for UCP in the mitochondria of BAT. These findings suggest that a marked decrease in BAT thermogenic capacity and activity is noted in old obese mice, probably due to synergism of aging and obesity.


Subject(s)
Adipose Tissue, Brown/metabolism , Aging/metabolism , Animals , Body Weight , Guanosine Diphosphate/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Obese , Proteins/metabolism , RNA, Messenger/metabolism
9.
J Dairy Sci ; 80(10): 2330-9, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9361205

ABSTRACT

The effects were examined of a pepsin hydrolysate of bovine lactoferrin on the proliferation of murine splenocytes. The hydrolysate enhanced [3H]thymidine uptake by splenocytes, but undigested bovine lactoferrin exerted an inhibitory effect. The hydrolysate had the ability to inhibit the blastogenesis that was induced by mitogens such as concanavalin A, phytohemagglutinin, and lipopolysaccharide; inhibition was similar to that with undigested lactoferrin. These results suggested that the hydrolysate contained both immunostimulatory and immunoinhibitory peptides. The stimulatory effect of the hydrolysate in the absence of mitogens was then explored in more detail using nonadherent splenocytes. The proliferative response of splenocytes to the hydrolysate was much greater in the fraction that was enriched with B cells than in the fraction that was enriched with T cells. The hydrolysate did not affect thymocyte proliferation. These data indicated that the adherent cells resembling macrophages and found among the splenocytes were not the target cells of the hydrolysate. The stimulatory effect of the hydrolysate was due to the activation of B cells by the hydrolysate and enhanced immunoglobulin production by splenocytes. Because the hydrolysate also enhanced the proliferation and immunoglobulin A production of Peyer's Patch cells, the immunostimulatory effect of the hydrolysate in vivo was examined using mice that had been orally immunized with cholera toxin. The concentrations of immunoglobulin A conjugated against cholera toxin in bile and in the intestinal contents of mice fed liquid diets containing 1% (wt/vol) lactoferrin hydrolysate were greater than those of mice fed control diets. This result suggested that the use of the lactoferrin hydrolysate is beneficial to enhance mucosal immunity.


Subject(s)
Adjuvants, Immunologic/pharmacology , Lactoferrin/metabolism , Lactoferrin/pharmacology , Pepsin A/metabolism , Peyer's Patches/immunology , Spleen/immunology , Animals , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Cattle , Cell Division/drug effects , Concanavalin A/pharmacology , Female , Hydrolysis , Immunoglobulins/biosynthesis , Lipopolysaccharides/pharmacology , Lymphocyte Activation/drug effects , Mice , Mice, Inbred BALB C , Mice, Inbred C3H , Mice, Nude , Mitogens/pharmacology , Peyer's Patches/drug effects , Phytohemagglutinins/pharmacology , Spleen/drug effects
10.
J Cell Physiol ; 170(2): 101-5, 1997 Feb.
Article in English | MEDLINE | ID: mdl-9009138

ABSTRACT

The effects of lactoferrin (Lf), an iron-binding glycoprotein, on cell migration were investigated. Lf inhibited the cell migration of three gastrointestinal cell lines (Caco-2 cells, AGS cells, and IEC-18 cells) in vitro. Both iron-saturated (holo) and iron-depleted (apo) Lf showed this inhibitory effect. Chelation of iron in the culture medium by desferrioxamine did not affect the activity of either form of Lf. A pepsin hydrolysate of Lf exhibited effectiveness similar to that of intact Lf. These results demonstrate a novel activity of Lf and suggest a potential role for this molecule in gastrointestinal wound healing, which is independent of its iron-binding capacity.


Subject(s)
Cell Movement/drug effects , Digestive System Physiological Phenomena , Lactoferrin/pharmacology , Adenocarcinoma , Animals , Apoproteins/pharmacology , Cattle , Colonic Neoplasms , Deferoxamine/pharmacology , Humans , Intestinal Mucosa , Kinetics , Rats , Stomach Neoplasms
12.
Pigment Cell Res ; 10(6): 410-3, 1997 Dec.
Article in English | MEDLINE | ID: mdl-9428009

ABSTRACT

The effects of whey proteins from bovine milk on melanogenesis in cultured human melanocytes were examined. Among the major protein components of milk whey including beta-lactoglobulin (BLG), alpha-lactalbumin, serum albumin, and IgG, only BLG exhibited the depigmenting effect at a concentration of 1 mg/ml. Also, BLG suppressed the activity of tyrosinase in these cells. Retinol, to which BLG is known to bind, slightly increased the pigmentation of the cells at concentrations in the range of 1-100 nM, and retinoic acid, a metabolite of retinol, exhibited a strong pigmentation-promoting effect within the same concentration range. Treatment of the cells with 1 mg/ml BLG completely abrogated the pigmentation induced by these A vitamins. These results demonstrate a novel biological activity of BLG and suggest that this activity is dependent on its ability to bind retinol.


Subject(s)
Lactoglobulins/pharmacology , Melanins/biosynthesis , Melanocytes/drug effects , Melanocytes/metabolism , Animals , Cattle , Cells, Cultured , Enzyme Activation/drug effects , Humans , Melanocytes/cytology , Melanocytes/enzymology , Monophenol Monooxygenase/antagonists & inhibitors , Pigmentation/drug effects , Vitamin A/pharmacology
13.
Occup Med (Lond) ; 46(5): 356-60, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8918150

ABSTRACT

This study was undertaken to clarify the beliefs and attitudes of Japanese businesses towards AIDS. Questionnaires were mailed to 1,655 Japanese companies listed on the Tokyo Stock Exchange in June 1993, and the response rate was 38% (n = 620). About 60% of the responding companies had already implemented or were developing AIDS measures. Only 7% of the companies had an AIDS policy, and 5% of the companies were developing one. Eighty-five per cent of the companies perceived AIDS education as necessary, while 53% of the companies replied that HIV testing was unnecessary. As reasons for providing AIDS education, avoiding discrimination and anxiety in the workplace were frequently cited. Ninety-five per cent of the companies wanted guidelines or manuals for AIDS to be developed by the Ministry of Labour, or to have training courses for personnel in charge of education or counselling provided by the Ministry. Although AIDS measures are currently unsatisfactory in Japanese businesses, they are expected to develop effective measures, considering their high recognition of the need for AIDS education.


Subject(s)
Acquired Immunodeficiency Syndrome/prevention & control , Commerce , Health Knowledge, Attitudes, Practice , Adult , Attitude to Health , HIV Infections/prevention & control , Health Education/methods , Health Education/trends , Health Policy , Humans , Japan , Middle Aged , Surveys and Questionnaires
14.
Pigment Cell Res ; 9(5): 235-9, 1996 Oct.
Article in English | MEDLINE | ID: mdl-9014209

ABSTRACT

The effects of bovine milk proteins on melanogenesis in B16 cells were examined. Both whey protein isolate and casein exhibited depigmenting properties. Among the major protein components of milk--including beta-lactoglobulin, alpha-lactalbumin, alpha-, beta-, and kappa-casein--only kappa-casein exhibited the depigmenting effect. However, the carboxyl terminal peptide of kappa-casein, glycomacropeptide, did not show this activity. Also, kappa-casein promoted the proliferation of the cells and inhibited the activity of tyrosinase in the cells. These results indicate that kappa-casein acts as a melanogenesis-suppressing modulator.


Subject(s)
Caseins/pharmacology , Melanocytes/drug effects , Pigmentation/drug effects , Animals , Cattle , Cell Division , Melanins/analysis , Melanocytes/cytology , Melanocytes/enzymology , Melanoma , Mice , Milk Proteins/pharmacology , Monophenol Monooxygenase/metabolism , Tumor Cells, Cultured , Whey Proteins
15.
J Pediatr ; 128(6): 834-40, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8648544

ABSTRACT

OBJECTIVES: House dust mite (HDM) is a representative inhalant allergen that triggers allergic disease in childhood. The aim of this study is early detection of HDM-specific IgE antibody and prediction of the risk of a positive reaction to this antibody by in vitro parameters in infants with allergic manifestations. STUDY DESIGN: Levels of HDM IgE in a range below the standard cutoff point of 0.35 U/ml, serum concentrations of IgE, and specific IgE antibodies against egg white, cow milk, and soybeans were determined in 108 infants with allergic manifestations at 6 months of age, and these infants were monitored for conversion of HDM IgE to positive levels greater than 0.35 U/ml up to 5 years of age. The presence of active allergic disease at 5 years of age in relation to HDM-specific IgE was also examined. RESULTS: We were able to determine reliably the HDM IgE values between 0.23 and 0.35 U/ml, using a fluorescent enzyme immunoassay that measured the intensity of fluorescence. The HDM IgE levels increased, resulting in positive values, in 54 of 108 subjects during the first 5 years of life. In multiple regression analysis, an HDM IgE value between 0.23 and 0.35 U/ml, a high serum IgE level, and a positive reaction to specific IgE antibody against egg white in infants at 6 months of age proved to be significant predictors of the future positive reaction to HDM IgE (p = 0.0006, 0.0043, and 0.0001). In particular, the sensitivity and specificity of specific IgE antibody against egg white for the conversion of HDM IgE to positive values were the best among these indicators. Moreover, active allergic diseases were observed significantly more often in children with positive HDM IgE values than in children with negative HDM IgE values at 5 years of age (p < 0.001 for each). CONCLUSIONS: A determination of these predictors in infants at 6 months of age can be used for early detection of HDM IgE and would be valuable in a screening test for later allergic disease among infants with allergic manifestations.


Subject(s)
Allergens/immunology , Antibody Specificity/immunology , Dust , Immunoglobulin E/blood , Mites/immunology , Animals , Child, Preschool , Female , Follow-Up Studies , Food Hypersensitivity/diagnosis , Food Hypersensitivity/immunology , Humans , Infant , Male , Prospective Studies , Respiratory Hypersensitivity , Risk Factors
16.
Biosci Biotechnol Biochem ; 60(3): 521-3, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8901116

ABSTRACT

Human or bovine lactoferrin (LF) and lactoferricin (LFcin), a peptide derived from the N-terminal region of LF, each have the ability to stimulate the release of neutrophil-activating polypeptide interleukin 8 (IL-8) from human polymorphonuclear leukocytes (neutrophils, PMNs). This finding suggests that LF and LFcin may both function as immunomediators for activating the host defense system. A basic peptide, protamine, exerted the same effect as that of LF and LFcin, suggesting the importance of the basic nature of LF and LFcin in acting as an inducer of IL-8 release from PMNs.


Subject(s)
Anti-Infective Agents/pharmacology , Interleukin-8/metabolism , Lactoferrin/analogs & derivatives , Lactoferrin/pharmacology , Neutrophils/drug effects , Neutrophils/metabolism , Amino Acid Sequence , Animals , Cattle , Cells, Cultured , Humans , Molecular Sequence Data
17.
Infect Immun ; 64(3): 1075-7, 1996 Mar.
Article in English | MEDLINE | ID: mdl-8641764

ABSTRACT

Bovine lactoferrin strongly inhibited the hemagglutination activity of type 1 fimbriated Escherichia coli. In addition, it agglutinated these bacteria. The agglutination reaction was specifically inhibited by glycopeptides derived from bovine lactoferrin or alpha-methyl-D-mannoside. These observations indicate that the glycans of bovine lactoferrin can serve as receptors for type 1 fimbrial lectin.


Subject(s)
Escherichia coli/metabolism , Lactoferrin/metabolism , Lectins/metabolism , Polysaccharides/metabolism , Receptors, Immunologic/metabolism , Agglutination , Animals , Cattle , Guinea Pigs , Hemagglutination
18.
Occup Med (Lond) ; 46(1): 12-6, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8672787

ABSTRACT

This paper reports the activities of occupational health organizations in Japan, taking Nishinihon Occupational Health Service Center, one of the largest scale occupational health service providers, as an example. The organizations, at the request of enterprises, provide occupational health services on a profit basis especially for small- and medium-scale enterprises which lack the human resources and/or facilities to meet legal requirements on occupational health. The main services include: (1) providing various types of medical examinations for workers, (2) measuring work environment, (3) occupational physicians and occupational health nurses providing a comprehensive service. Among these services, legally required health examinations and work environment measurements are well served even for small-scale enterprises. Less effective are the health promotion and occupational health service by the occupational health staffs. In the future, these service will be better provided by a newly developed network system to support occupational heath activities in small-scale enterprises.


Subject(s)
Industry , Occupational Health Services , Japan , Occupational Health , Occupational Health Services/standards , Occupational Health Services/trends
19.
Appl Environ Microbiol ; 61(11): 4131-4, 1995 Nov.
Article in English | MEDLINE | ID: mdl-8526530

ABSTRACT

Feeding of bovine milk to mice induced a high incidence of bacterial translocation from the intestines to the mesenteric lymph nodes, and the bacteria involved were mainly members of the family Enterobacteriaceae. Supplementation of the milk diet with bovine lactoferrin or a pepsin-generated hydrolysate of bovine lactoferrin resulted in significant suppression of bacterial translocation. Our findings suggest that this ability of lactoferrin to inhibit bacterial translocation may be due to its suppression of bacterial overgrowth in the guts of milk-fed mice.


Subject(s)
Intestines/drug effects , Intestines/microbiology , Lactoferrin/pharmacology , Administration, Oral , Animals , Cattle , Cell Division/drug effects , Diet , Enterobacteriaceae/drug effects , Enterobacteriaceae/growth & development , Enterobacteriaceae/isolation & purification , Feces/microbiology , Female , Intestines/anatomy & histology , Lactoferrin/administration & dosage , Lymph Nodes/microbiology , Mesentery/microbiology , Mice , Mice, Inbred BALB C , Milk
20.
Biosci Biotechnol Biochem ; 59(10): 1875-81, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8534979

ABSTRACT

The cell growth-stimulating activity of lactoferrin (LF) in combination with epidermal growth factor (EGF) was evaluated by using a rat intestinal epithelial cell line, IEC-18. LF was found to be more effective than EGF for inducing an increase in cell numbers when cultured for over 6 days using a medium containing 0.2% fetal calf serum (FCS), although the 3H-thymidine incorporation-stimulating activity of EGF was more potent than that of LF. A synergistic effect of LF and EGF was observed in both cell proliferation and DNA synthesis assays. The increase in cell numbers when stimulated with LF plus EGF corresponded to about 5 times that of the control. Iron was not required for manifestation of these effects of LF. On the other hand, iron-saturated transferrin (TF) had cell-growth-stimulating activity, but iron-free TF did not, either in the presence or absence of EGF. These results indicate that LF induces cell proliferation by a mechanism distinct from that of TF. A pepsin-generated hydrolysate of LF (LFH) had an activity similar to that of undigested LF, and a peptide with cell-growth-stimulating activity from bovine LFH was isolated by monitoring its effects in combination with EGF on DNA synthesis in IEC-18 cells. Sequence analysis indicated that the peptide has the structure Ala-Glu-Ile-Tyr-Gly-Thr-Lys-Glu-Ser-Pro-Gln-Thr-His-Tyr-Tyr, corresponding to residues 79-93 of bovine LF.


Subject(s)
Cell Division/drug effects , Epidermal Growth Factor/pharmacology , Lactoferrin/pharmacology , Amino Acid Sequence , Animals , Cattle , Cell Line , DNA/biosynthesis , Humans , Hydrolysis , Intestinal Mucosa/cytology , Molecular Sequence Data , Pepsin A/metabolism , Peptide Fragments/pharmacology , Rats , Transferrin/pharmacology
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