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At least 19 recordsLinked to original sources

Murine natural antitumor antibodies. III. Interferon treatment of a natural killer-resistant lymphoma: augmentation of natural antibody reactivity and susceptibility to in vivo natural resistance.

Treatment of a natural killer cell-resistant (NKR) DBA/2 lymphoma with L-cell interferon (IFN) enhanced its reactivity to serum natural antibody in vitro in cytolysis and absorption studies and increased the in vivo acquisition of natural and antitumor antibody in the peritoneal cavity. The IFN effects were both time- and dose-dependent. In vitro IFN-treated, [131I]5-iodo-2'-deoxyuridine-labeled tumor cells, when injected ip into normal syngeneic mice, were more rapidly eliminated than were untreated control cells. IFN treatment of the NKR tumor decreased "cold-target" inhibition of NK lysis and did not alter binding or lysis by macrophages. These findings indicated that the enhancement of natural resistance to the IFN-treated tumor did not involve NK cells or macrophages and suggested that IFN may enhance host antitumor resistance by increasing tumor reactivity to antibody.

Animals↗

Natural killer cell immunodeficiency in siblings: defective killing in the absence of natural killer cytotoxic factor activity in natural killer and lymphokine-activated killer cytotoxicities.

A immunodeficiency of natural killer cells as effectors for natural killer and lymphokine-activated killer cytotoxicities was first demonstrated in siblings. Two of three male siblings persistently lacked natural killer activity against K562 target cells as assayed by a 51Cr-release assay: percent lysis values were less than 1.0% as compared to the normal lymphocyte values of 43.5% +/- 6.2% (mean +/- SD). Their lymphocytes did not develop natural killer cell activity by changing effector to target ratios, prolonging the incubation time, or stimulating them with interferon-alpha or interleukin 2. Numbers of lymphocytes bearing Leu-7, CD16, or NKH-1 were normal but those of Leu-7-, CD16+ cells were decreased as estimated by flow cytometry. Single cell-in-agarose assays showed normal numbers of natural killer cells capable of binding to a target cell but incapable of killing it. They had depressed levels of lymphokine-activated killer activity, which was totally eliminated by the treatment with OKT3 and complement. This result indicates that the patients' natural killer cells are also defective in the capacity to work as effectors for lymphokine-activated killer activity. The patients' natural killer cells did not produce natural killer cytotoxic factor activity. Antibody-dependent cellular cytotoxicity and cytotoxic T lymphocyte cytotoxicity were normal. These results demonstrate a selective natural killer cell deficiency as effectors for natural killer and lymphokine-activated killer cytotoxicities with a familial tendency, in which there is defective killing with the absence of natural killer cytotoxic factor activity.

Child↗

Natural killer cell immunodeficiency in patients with chronic myelogenous leukemia. IV. Interleukin-1 deficiency, gamma-interferon deficiency and the restorative effects of short-term culture in the presence of interleukin-2 on natural killer cytotoxicity, natural killer-target binding and production of natural killer cytotoxic factor.

We report herein that defective natural killer (NK) cell cytotoxicity, NK cytotoxic factor (NKCF) production and NK target binding ability of patients with chronic myelogenous leukemia (CML) are functionally restorable after short-term culture (less than 1 week) with recombinant interleukin-2 (rIL-2). We have previously reported that, despite normal to increased numbers of CD16+ large granular lymphocytes, fluorescence-activated-cell-sorted NK cells from CML patients are profoundly defective in NK cell activity and are unable to lyse the CML blast-crisis-derived, NK-sensitive target K562. Since we and others have also previously shown that the defective NK cytotoxicity from CML patients is restorable after 1-4 weeks of incubation with rIL-2, we therefore deemed it important to study the kinetics of IL-2-mediated NK restoration at earlier time intervals (less than 1 week). In the present report, we have demonstrated a significant restoration of NK cell cytotoxicity in CML patients against K562 after 5 days of short-term culture with rIL-2. In addition, recovery of NKCF production and restoration of target-binding capacity to normal levels by NK cells from CML patients were also observed after short-term (less than 1 week) rIL-2 treatment. Finally, we have demonstrated in the present report that adherent cells and peripheral-blood lymphoid cells from CML patients, as compared to normal controls, are unable to produce IL-1 beta and interferon-gamma, respectively, after stimulation with phorbol myristate acetate (IL-1 beta) and phytohemagglutinin-M (interferon-gamma).

Antigens, CD↗

Natural cytolytic activity in mice with natural or induced cellular defects. I. Differential ability of in vitro interleukin-2 addition to augment natural cytolytic function.

The ability of in vitro addition of recombinant interleukin 2 (rIL-2) to differentially enhance natural cytotoxicity was assessed using cells from mice with natural and induced cellular defects. In vivo treatment with most immunosuppressive or cytoreductive agents, anti-asialo-GM1 antibody, or gamma irradiation dramatically reduced in vitro cytotoxicity against natural killer (NK) sensitive targets by direct reduction in either percentage specific lysis or lytic units per spleen. In most cases, in vitro addition of rIL-2 (at concentrations causing augmented NK function in cells from naive Balb/C mice) enhanced cytotoxic activity of cells from treatment groups to a normal value but not within the rIL-2-enhanced range of nontreated animals. Additionally, cytotoxic activity of cells from animals treated with certain drugs or gamma irradiation could be augmented by rIL-2 when measured by percentage lysis but not lytic units per spleen. In vivo treatment with cyclosporin A did not affect natural cytotoxic activity and addition of rIL-2 augmented the NK activity in a similar fashion to the profile of naive cells. In experiments using cells from beige (C57Bl/6-bg) mice which have a natural defect in NK activity against YAC-1 targets, addition of rIL-2 (at concentrations causing augmented natural cytotoxic function in cells from C57Bl/6 mice) could not effectively enhance in vitro natural cytotoxic function.

Adjuvants, Immunologic↗

Natural cytotoxic T cells (NCTC) that differ from natural killer (NK) and natural cytotoxic (NC) cells are present in Peyer's patches of mice.

We have examined noninduced cytotoxicity of mouse gut associated and peripheral lymphoid tissues for a wide variety of syngeneic as well as allogeneic cell lines and lymphoblasts. Lymphoid cells from Peyer's patches were found to lyse these targets in a 3-hr chromium release assay whereas lymphoid cells from intestinal mucosa, mesenteric or peripheral lymph nodes, spleen, and thymus did not. The variety of targets toward which Peyer's patch cells were cytotoxic established the latter as nonspecific and H-2 unrestricted. The cell responsible for the lytic event was identified as possessing Thy 1.2 and Ia surface antigens. This naturally cytotoxic T cell (NCTC) was found to be adherent to nylon-wool but not to plastic plates. Although both natural killer cell (NK) and non-NK targets served as targets for the NCTC, the latter were further differentiable from NK cells by lack of asialo GM1 surface marker, which is present on NK cells. In addition, NCTC remained fully functional in mice given either of the drugs cyclophosphamide or cortisone. Each of these drugs, in the doses used, markedly reduced poly(I:C)-induced NK activity. Thus, NCTC differs from NK on the basis of the spectrum of targets against which it is functional, phenotypic surface markers, insusceptibility to stimulation with poly(I:C), and insensitivity to diminution by the immunosuppressive drugs cyclophosphamide and hydrocortisone. Since NCTC is a Thy 1.2 antigen-bearing cell and is detectable in a 3-hr cytotoxic assay, it also differs from the natural cytotoxic (NC) cell. NC lacks the Thy 1.2 marker and becomes detectable only in an 18-hr cytotoxic assay. Thus, NCTC is neither an NK nor an NC cell. We have discussed the possibility that the three naturally occurring cells may be related by being dedifferentiated descendants of an antigen-specific cytotoxic T lymphocyte (CTL). Alternatively, since NCTC is confined to an anatomical site prone to ample antigenic exposure and is still identifiable as a T cell, it may be in linear transition from the CTL to the NK or NC stages.

Animals↗

Natural cytotoxic cells against solid tumors in mice. IV. Natural cytotoxic (NC) cells are not activated natural killer (NK) cells.

Natural cell-mediated cytotoxicity (NCMC), measured against a variety of tumors, is mediated by at least two sub-populations of effector cells: natural cytotoxic (NC) and natural killer (NK). The studies described in this report show that target lysis by NC cells requires a prolonged (18- to 24 h) assay period, whereas NC-susceptible targets can be lysed in short-term (4h) [3H]-proline assays using allo-sensitized CTL or mitogen-activated cytotoxic populations. NC cells are not "activated" during the long-term assay as indicated by: (1) demonstrating that lysis of NC-susceptible targets in long-term (20 h) 51Cr assays is still the function of a Qa-5- effector cell (NC) and (2) the fact that preincubation of the NC effector cell with susceptible targets for 18 h did not result in the activation of an NK-like population (kinetics of target lysis were comparable to those noted with fresh NC cell preparations). We show that NC cell activity is preserved in both the beige mutant and the PL/J mouse strains, both of which exhibit low NK cell activity, even in long-term assays. These combined studies support the view that NC and NK cell activities are the function of distinct cell types and not the property of a single cell class under different states of activation.

Animals↗

Recognition specificities, development, and possible biological function of natural killer cells in the mouse. I. Spleen focus forming assay for natural killer activity and analysis of lectin-like recognition structures on the surface of murine natural killer cells.

A number of simple sugars have been tested and found to be effective in blocking lysis of YAC-1 tumor target cells by nonimmune murine natural killer (NK) effector cells. Using a spleen fragment culture system an assay has been developed which allows us to compare the inhibition of lysis observed in replicate culture wells prepared from cells contained in one spleen fragment (less than or equal to 1 X 10(6) cells). The inhibition pattern of any well was found to fall naturally into 1 of 25 (of the total 128 possible tested) patterns. Using this panel analysis of NK activity in individual mice of the same or different strain has been compared. Our data suggest that within any given strain the inhibition pattern of NK effector cells is quite uniform. Consistent differences are seen between strains which are interpreted in terms of a genetic control of the final expression of the NK recognition repertoire. In adult F1 hybrid individuals the pattern of recognition by NK cells is best considered a result of the codominant expression of genes contributed by each parent.

Animals↗

[Natural history of chromoblastomycosis in Madagascar and the Indian Ocean] [Natural history of chromoblastomycosis in Madagascar and the [Natural history of chromoblastomycosis in Madagascar and the Indian Ocean].

The natural history of chromoblastomycosis was studied in Madagascar by analysing the characteristics of 1323 confirmed cases observed since 1955, including 45 patients receiving a new antifungic drug (terbinafine) during a multicentric study organized in 1995. The surveys data, conserved by the histopathology laboratory in the Institut Pasteur of Madagascar during 40 years, permit this retrospective analysis. The description of two ecosystems, one in the North with Fonsecaea pedrosoi evolving in the tropical rainforest and one in the South with Cladophialophora carrionii (41% of the whole sample) isolated in the spiny desert, demonstrates that the deforestation, in order to product charcoal and to build houses, is the primary factor associated with this disease. The epidemiologic (87% of patients are male and 96% are more than 16 years old, with more than 74% of the lesions located on feet and legs), mycologic (62% of the isolated strains belong to the F. pedrosoi species) and therapeutic (low efficiency of thiabendazole in long-term lesions, high efficiency of terbinafine especially on recent lesions and on Cladophialophora-infected patients) aspects of the natural history of chromomycosis confirmed that Madagascar is the most important focus in the world (global prevalence of about 1 for 8500 inhabitants), with few sporadic cases in the other islands of the Indian Ocean (La Reunion, Comoro islands and Mayotte). In the difficult context of Madagascar, the need for a non-specialized laboratory-applicable diagnostic technique that provides infection and species identification led the Institut Pasteur de Madagascar to develop an ELISA-based technique. A large-scale control throughout the country, with the assessment of effective oral chemotherapy with terbinafine, is seen as possible by the authors with the help of the manufacturer.

Antifungal Agents↗

Expression patterns of lectin-like natural killer receptors, inhibitory CD94/NKG2A, and activating CD94/NKG2C on decidual CD56bright natural killer cells differ from those on peripheral CD56dim natural killer cells.

The balance of inhibitory and activating natural killer (NK) receptors on maternal decidual NK cells, most of which are CD56bright, is thought to be crucial for the proper growth of trophoblasts in placenta. A lectin-like NK receptor, CD94/NKG2, is the receptor for human leukocyte antigen (HLA)-E, which is expressed on trophoblasts. To clarify the mechanism regulating the activity of decidual NK cells during pregnancy, we investigated the expression patterns of inhibitory NK receptor, CD94/NKG2A, and activating receptor, CD94/NKG2C, on decidual NK cells in an early stage of normal pregnancy and compared them with those on peripheral NK cells, most of which are CD56dim. The rate of NKG2A-positive cells was significantly higher for decidual CD56bright NK cells than for peripheral CD56dim NK cells, but the rates of NKG2C-positive cells were comparable between the two cell types. Interestingly, peripheral CD56dim NK cells reciprocally expressed inhibitory NKG2A and activating NKG2C, but decidual CD56bright NK cells that expressed activating NKG2C simultaneously expressed inhibitory NKG2A. The co-expression of inhibitory and activating NKG2 receptors may fine-tune the immunoregulatory functions of the decidual NK cells to control the trophoblast invasion in constructing placenta.

CD56 Antigen↗

Depressed natural killer cell activity due to decreased natural killer cell population in a vitamin E-deficient patient with Shwachman syndrome: reversible natural killer cell abnormality by alpha-tocopherol supplementation.

UNLABELLED: Natural Killer (NK) cell activity was examined in a 16-month-old Japanese boy with Shwachman syndrome associated with severe vitamin E deficiency. As evaluated by 51Cr-release assay from K562 cells, NK cell activity was constantly decreased. After 8 weeks of oral alpha-tocopherol (alpha-Toc) supplementation (100 mg/day), NK cell activity had normalised. When alpha-Toc supplementation was interrupted for 16 weeks. NK cell activity again decreased. Flow cytometry of peripheral lymphocytes revealed a lowered number of CD16+ CD 56- fraction, which has the most potent NK cell activity. Single cell-in-agarose assay, to investigate the binding and cytolytic activity of NK cell at the single cell level, revealed that the number of NK cells which bind to K562 cell was decreased, but that the cytolytic activity of the individual binding cell was relatively unaffected. A second supplementation of alpha-Toc for 8 weeks successfully restored NK cell activity, the number of cells expressing NK cell markers and the number of K562-binding cells as compared to the age-matched normal range. CONCLUSION: These results indicate that severe vitamin E deficiency caused impaired NK cell activity due to a decrease in the number of CD16+ CD56- NK cells and that this abnormality is reversible with alpha-Toc supplementation.

Adolescent↗

Natural killer cells in murine muscular dystrophy. IV. Characterization of Percoll fractionated splenic and thymic natural killer cells and natural killer-sensitive thymocyte targets.

The Natural Killer (NK) activity in the thymus and NK-sensitive thymocyte targets of dystrophic mice was investigated. Dystrophic and normal mouse thymocytes or spleen cells were layered on discontinuous Percoll gradients (5 or 10% increments, respectively) between 40 and 70% and centrifuged at 1700 g for 30 min. All fractions were tested for either NK activity or used a 51Cr-labeled NK-sensitive targets in a 6-hr 51Cr release assay. The density interface between the 50% (1.060 g/ml) and 60% (1.075 g/ml) Percoll fractions of either dystrophic or normal mouse spleen cells and the 40% (1.050 g/ml) and 50% (1.060 g/ml) Percoll fractions of either dystrophic or normal mouse thymocytes were found to contain the largest proportion of NK activity using YAC-1 lymphoma tumor cells as targets. In addition, the NK activity in dystrophic mouse spleen cells and thymocytes was significantly greater when compared with normal mouse controls. Target binding cell studies revealed that these Percoll fractions of dystrophic mouse spleen cells and thymocytes had greater numbers of conjugate-forming cells when compared with normal control groups. Cell depletion experiments using either anti-Thy 1.2, anti-asialo-GM 1 or anti-NK-1 plus complement treatment revealed that the cell responsible for NK activity in the 50% Percoll fraction interface of dystrophic mouse spleen cells was asialo-GM 1 positive. NK-1 positive, and partially Thy 1.2 positive. However, the cells displaying NK-activity in the thymus of normal or dystrophic mice were found to be highly Thy-1.2 positive and peanut agglutinin (PNA) negative. The density interface between the 60% (1.075 g/ml) and 65% (1.081 g/ml) Percoll fractions of either normal or dystrophic mouse thymocytes contained the largest proportion of NK-sensitive target cells. Interestingly, the 60% Percoll fraction of dystrophic mouse thymocyte targets was significantly more susceptible to NK-mediated lysis than that of the normal mouse thymocyte population. Cell depletion experiments revealed that the NK-sensitive thymocyte population was similar in both mice, that is, Thy-1.2 positive, cortisone sensitive, PNA positive, Dolichos biflorus (DBA) negative and asialo GM-1 negative. The results indicate that there are density differences between splenic and thymic NK cells. In addition, there are density and phenotypic differences between thymic NK cells and thymic NK-sensitive target cells. The findings support the hypothesis that there are different populations of NK cells.

Animals↗

Natural surfactant extract versus synthetic surfactant for neonatal respiratory distress syndrome.

BACKGROUND: This section is under preparation and will be included in the next issue. OBJECTIVES: To compare the effect of synthetic surfactant to natural surfactant in premature infants with established respiratory distress syndrome. SEARCH STRATEGY: Searches were made of the Oxford Database of Perinatal Trials, Medline (MeSH terms: pulmonary surfactant; limits: age groups, newborn infant; publication type, clinical trial), previous reviews including cross references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language. SELECTION CRITERIA: Randomized controlled trials comparing administration of synthetic surfactants to administration of natural surfactant extracts in premature infants with respiratory distress syndrome were considered for this review. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including pneumothorax, patent ductus arteriosus, necrotizing enterocolitis, intraventricular hemorrhage (all intraventricular hemorrhage and severe intraventricular hemorrhage), chronic lung disease, retinopathy of prematurity, and mortality were excerpted by the primary reviewer (R. Soll). Data analysis was conducted according to the standards of the Neonatal Cochrane Review Group. MAIN RESULTS: The meta-analysis supports a significant reduction in the risk of pneumothorax (typical relative risk 0.68, 95% CI 0.56, 0.83; typical risk difference -0.04 95% CI -0.06, -0.02). No disadvantages to natural surfactant extract treatment are noted regarding other outcomes. A trend towards reduced mortality is noted in association with natural surfactant extract treatment. REVIEWER'S CONCLUSIONS: Both natural surfactant extracts and synthetic surfactant extracts are effective in the treatment of established respiratory distress syndrome. Comparative trials demonstrate greater early improvement in the requirement for ventilatory support and fewer pneumothoraces associated with natural surfactant extract treatment. On clinical grounds, natural surfactant extracts would seem to be the more desirable choice.

Biological Products↗

Prospective randomized trial of natural interferon-alpha versus natural interferon-alpha plus cimetidine in advanced renal cell carcinoma with pulmonary metastasis.

PURPOSE: In a preliminary non-randomized study, combination therapy with natural (i.e. non-recombinant) interferon-alpha plus cimetidine obtained a high response rate in patients with advanced renal cell carcinoma. We conducted a prospective randomized phase III trial to determine whether combination therapy with natural interferon-alpha plus cimetidine is superior to natural interferon-alpha alone in patients with advanced renal cell carcinoma with pulmonary metastasis. METHODS: Patients received 5 million units (MU) natural interferon-alpha per day, five times a week, or the 5 MU natural interferon-alpha regimen plus a daily oral cimetidine. The primary and secondary end points were the response rate, and the time to progression (TTP), respectively. RESULTS: Between April 1998 and March 2002, 71 patients from 32 institutions were randomly assigned to the 2 treatment groups. One patient in each group did not receive any natural interferon-alpha whatsoever. Two patients in the natural interferon-alpha alone group stopped treatment: on day 9 and on day 10, respectively. In the intent-to-treat analysis, 1 complete response (CR), 4 partial responses (PRs), 16 no changes (NCs), and 12 progressive diseases (PDs) were observed among the 36 patients in the interferon-alpha alone group with a response rate of 13.9%. Of the 35 patients in the natural interferon-alpha plus cimetidine group, there were two CRs, 8 PRs, 13 NCs, and 11 PDs, yielding a response rate of 28.6% (P=0.13). TTP ranged from 9 to 845 days (median 112 days) in the natural interferon-alpha-alone group, and from 31 to 1,568 days (median 125 days) in the natural interferon-alpha plus cimetidine group (P=0.87). CONCLUSIONS: Combined treatment with natural interferon-alpha plus cimetidine for advanced renal cell carcinoma did not result in a significant improvement in response rates or TTP compared to natural interferon-alpha therapy alone.

Adult↗

Women's beliefs about "natural" hormones and natural hormone replacement therapy.

OBJECTIVE: To assess women's beliefs about natural hormones, including what they believe the term "natural" means, and their beliefs about the risks, side effects, and efficacy of natural hormone replacement compared to standard hormone replacement. DESIGN: Eighty-two women completed a 20-item survey available at a local compounding pharmacy. Respondents were white (100%), middle-aged (mean age, 47.22 years), and college educated (95.1%); 32.9% were perimenopausal, and 50.0% were postmenopausal; 58.5% were currently using hormone replacement therapy and, of those, 77.1% were using human bio-identical hormones. RESULTS: Ninety percent of the respondents ( n = 74) reported that they had heard about natural hormones. Of those, most believed natural meant plant-derived (44.6%) and/or not synthesized or made without chemicals (50.0%). Most reported hearing about natural hormones from a healthcare provider (66.2%) and/or magazines and books (55.4%). When compared with standard hormone replacement, most respondents endorsed the beliefs that natural hormones have fewer or no risks (71.4%), have fewer or no side effects (69.0%), and are equally or more effective for managing menopause symptoms (61.8%). In addition, many endorsed the beliefs that natural hormone replacement is equally or more effective than standard hormone replacement for protection against osteoporosis (47.1%) and heart disease (40.0%), although many endorsed "don't know" for bone (45.7%) and heart (54.3%) protection. CONCLUSIONS: Among women responding to a survey in a compounding pharmacy, most believed that, compared with standard hormones, natural hormones are safer, cause fewer side effects, and are equally or more effective for symptom management. Many believed natural hormone replacement is equally or more effective for long-term bone and heart protection. Educating women on the nature, risks, and benefits of natural hormone therapy is recommended.

Adult↗

Genomic alterations in blastic natural killer/extranodal natural killer-like T cell lymphoma with cutaneous involvement.

Natural killer and natural killer-like T cell lymphomas represent a rare type of non-Hodgkin's lymphoma originally described to involve the upper aerodigestive tract. This malignancy has been increasingly observed in other extranodal sites, particularly in the skin. Patients with cutaneous natural killer cell lymphoma generally have a poor prognosis; however, the etiology and the underlying molecular pathogenesis remain unclear. This study aimed to investigate comprehensively genomic changes in blastic natural killer and extranodal natural killer-like T cell lymphoma with cutaneous involvement. Comparative genomic hybridization showed chromosome imbalances in six of eight cases studied (75%). The mean number of chromosome imbalances per sample was 2.18+/-1.63 with similar number of gains (1.18+/-1.17) and losses (1.00+/-1.34). The most frequent DNA copy number changes observed were losses of 9/9p (83%), followed by loss of 13q and gain of 7 (67%). Similar patterns of chromosome imbalances were observed in both blastic natural killer and cutaneous natural killer-like T cell lymphomas. Loss of the RB1 gene at 13q14.2 was detected in one blastic natural killer cell lymphoma with 13q loss using a gene dosage assay, and in one cutaneous natural killer-like T cell lymphoma without 13q loss using fluorescent in situ hybridization. Genomic microarray analysis identified oncogene copy number gains of PAK1 and JUNB in three of four cases studied, and gains of RAF1, CTSB, FGFR1, and BCR in two cases. Real-time polymerase chain reaction detected amplification of CTSB and RAF1 in four of five cases analyzed, JUNB and MYCN in three cases, and REL and YES1 in two cases, respectively. In conjunction with this study, an extensive literature search for the published G-banded karyotypes of four subsets of natural killer cell lymphomas was conducted, which showed a nonrandom pattern of multiple chromosome aberrations. These results reveal consistent genetic alterations in cutaneous natural killer cell lymphomas, and provide a basis for further investigation of molecular pathogenesis in this malignancy.

Chromosome Aberrations↗

Healthy nature healthy people: 'contact with nature' as an upstream health promotion intervention for populations.

Whilst urban-dwelling individuals who seek out parks and gardens appear to intuitively understand the personal health and well-being benefits arising from 'contact with nature', public health strategies are yet to maximize the untapped resource nature provides, including the benefits of nature contact as an upstream health promotion intervention for populations. This paper presents a summary of empirical, theoretical and anecdotal evidence drawn from a literature review of the human health benefits of contact with nature. Initial findings indicate that nature plays a vital role in human health and well-being, and that parks and nature reserves play a significant role by providing access to nature for individuals. Implications suggest contact with nature may provide an effective population-wide strategy in prevention of mental ill health, with potential application for sub-populations, communities and individuals at higher risk of ill health. Recommendations include further investigation of 'contact with nature' in population health, and examination of the benefits of nature-based interventions. To maximize use of 'contact with nature' in the health promotion of populations, collaborative strategies between researchers and primary health, social services, urban planning and environmental management sectors are required. This approach offers not only an augmentation of existing health promotion and prevention activities, but provides the basis for a socio-ecological approach to public health that incorporates environmental sustainability.

Health Promotion↗

Controversies: synthetic or natural surfactant. The case for natural surfactant.

Surfactant replacement therapy for respiratory distress syndrome (RDS) is not new, the first trials having been performed over 30 years ago. These early trials used synthetic protein-free surfactants administered as aerosols and were unsuccessful. Since 1980 a variety of natural and synthetic surfactant preparations have been used to treat or prevent RDS, and both demonstrate clinical effects. I have used evidence derived from 3 areas to demonstrate the superiority of natural surfactants: in vitro physical properties, in vivo physiological effects and the results of comparative clinical trials. using the pulsating bubble surfactometer, the surface tension at maximum and minimum bubble size are significantly lower for natural compared to synthetic surfactants (31 and 0 mN/m versus 53 and 29 mN/m respectively). Physiological effects of surfactants have been compared in immature rabbits and lambs and both models demonstrate the superiority of natural surfactants. For example in immature rabbits lung compliance values after 60 minutes of ventilation are 0.60 ml/cmH2O in natural surfactant treated animals, 0.44 ml/cmH2O in synthetic surfactant treated animals and 0.34 ml/cmH2O in controls (p < 0.01). The technique of meta-analysis was used to analyse the outcome of 6 comparative clinical trials of natural and synthetic surfactants. These 6 studies included 3536 babies and 5 of them compared Survanta (a bovine natural surfactant) and Exosurf (a synthetic protein-free surfactant). One study compared Infasurf (another bovine natural surfactant with Exosurf). Meta-analysis shows a 19% reduction in the odds of neonatal death for natural compared to synthetic surfactant treated babies (OR, 0.81; 95% CI 0.66-0.98). For bronchopulmonary dysplasia there was a non-significant reduction in risk for Survanta-treated babies (OR, 0.93; 95% CO 0.78-1.10). In summary, there is now clear evidence of physiological and clinical superiority of natural compared to synthetic surfactants. Surfactant proteins B and C are needed to facilitate rapid adsorption and spreading of phospholipids. They also account for the more rapid clinical action allowing oxygen and ventilator pressures to be lowered soon after administration. The odds of neonatal mortality are reduced by about 20% if natural surfactants are preferred to their synthetic protein-free counterparts. Long-term follow-up studies of babies treated with both types of surfactant should be a top priority.

Animals↗

Xenoreactive natural antibodies in the world of natural antibodies: typical or unique?

Xenoreactive natural antibodies are thought to be responsible for initiating the hyperacute rejection of porcine organs transplanted into primates. Progress has been made in recent years in the characterization of the specificity and functions of these antibodies. Xenoreactive natural antibodies recognize Gal alpha 1-3Gal, a carbohydrate related to the blood group A and blood group B antigens. The presence of Gal alpha 1-3Gal may not be sufficient to allow the binding of xenoreactive natural antibodies under physiological conditions; rather, the clustering of Gal alpha 1-3Gal determinants may dictate the extent to which xenoreactive natural antibodies attach to surfaces on which Gal alpha 1-3Gal is expressed. The predominant role of xenoreactive natural antibodies in the pathogenesis of hyperacute rejection in porcine-to-primate xenotransplantation involves the activation of complement. Complement activation is mediated by IgM, not IgG xenoreactive natural antibodies. Based on functional avidity, thermal binding optima, thermal liability and homogeneity of binding interactions, xenoreactive natural IgM appear to be members of a family of natural antibodies which includes isohaemagglutinins. The classification of xenoreactive antibodies and isohaemagglutinins into a family of antibodies may provide further insight into the nature and physiological functions of xenoreactive natural antibodies.

Animals↗