Microbiota of bovine milk, teat skin, and teat canal: Similarity and variation due to sampling technique and milk fraction.

The aim of this study was to evaluate the effect of sampling technique and milk fraction on bovine milk microbiota data and to compare the microbiota in milk to microbiota on the teat end and in the teat canal. Representative milk samples are highly important for assessment of bacteriological findings and microbiota in milk. Samples were obtained from 5 healthy lactating dairy cows at udder quarter level during 1 milking. Swab samples from the teat end and teat canal, and milk samples collected using different techniques and in different milk fractions were included. Milk was collected by hand stripping and through a teat canal cannula before and after machine milking, through a trans-teat wall needle aspirate after milking, and from udder quarter composite milk. The microbiota of the samples was analyzed with sequencing of the V1-V3 region of the 16S rRNA gene. In addition, somatic cell counts and bacterial cultivability were analyzed in the milk samples. Microbiota data were analyzed using multivariate methods, and differences between samples were tested using analysis of similarity (ANOSIM). Differences between samples were further explored via individual studies of the 10 most abundant genera. The microbiota on the teat end, in the teat canal, and in udder quarter composite milk, collected using a milking machine, differed in composition from the microbiota in milk collected directly from the udder quarter. No differences in milk microbiota composition were detected between hand-stripped milk samples, milk samples taken through a teat canal cannula, or milk samples taken as a trans-teat wall needle aspirate before or after milking. We conclude that for aseptic milk samples collected directly from the lactating udder quarter, sampling technique or milk fraction has minor effect on the microbiota composition.

Body mass index adjustments to increase the validity of body fatness assessment in UK Black African and South Asian children.

BACKGROUND/OBJECTIVES: Body mass index (BMI) (weight per height2) is the most widely used marker of childhood obesity and total body fatness (BF). However, its validity is limited, especially in children of South Asian and Black African origins. We aimed to quantify BMI adjustments needed for UK children of Black African and South Asian origins so that adjusted BMI related to BF in the same way as for White European children. METHODS: We used data from four recent UK studies that made deuterium dilution BF measurements in UK children of White European, South Asian and Black African origins. A height-standardized fat mass index (FMI) was derived to represent BF. Linear regression models were then fitted, separately for boys and girls, to quantify ethnic differences in BMI-FMI relationships and to provide ethnic-specific BMI adjustments. RESULTS: We restricted analyses to 4-12 year olds, to whom a single consistent FMI (fat mass per height5) could be applied. BMI consistently underestimated BF in South Asians, requiring positive BMI adjustments of +1.12 kg m-2 (95% confidence interval (CI): 0.83, 1.41 kg m-2; P<0.0001) for boys and +1.07 kg m-2 (95% CI: 0.74, 1.39 kg m-2; P<0.0001) for girls of all age groups and FMI levels. BMI overestimated BF in Black Africans, requiring negative BMI adjustments for Black African children. However, these were complex because there were statistically significant interactions between Black African ethnicity and FMI (P=0.004 boys; P=0.003 girls) and also between FMI and age group (P<0.0001 for boys and girls). BMI adjustments therefore varied by age group and FMI level (and indirectly BMI); the largest adjustments were in younger children with higher unadjusted BMI and the smallest in older children with lower unadjusted BMI. CONCLUSIONS: BMI underestimated BF in South Asians and overestimated BF in Black Africans. Ethnic-specific adjustments, increasing BMI in South Asians and reducing BMI in Black Africans, can improve the accuracy of BF assessment in these children.

The use of high-intensity focused ultrasound as a novel treatment for painful conditions-a description and narrative review of the literature.

High-intensity focused ultrasound (HIFU) is a non-invasive technique that allows a small, well-circumscribed thermal lesion to be generated within a tissue target. Tissue destruction occurs due to direct heating within the lesion and the mechanical effects of acoustic cavitation. HIFU has been used in a broad range of clinical applications, including the treatment of malignancies, uterine fibroids and cardiac arrhythmias. Interest in the use of the technique to treat pain has recently increased. A number of painful conditions have been successfully treated, including musculoskeletal degeneration, bone metastases and neuropathic pain. The exact mechanism by which HIFU results in analgesia remains poorly understood, but it is thought to be due to localised denervation of tissue targets and/or neuromodulatory effects. The majority of studies conducted investigating the use of HIFU in pain are still at an early stage, although initial results are encouraging. Further research is indicated to improve our understanding of the mechanisms underlying this treatment and to fully establish its efficacy; however, it is likely that HIFU will play a role in pain management in the future. This narrative review provides a synthesis of the recent, salient clinical and basic science research related to this topic and gives a general introduction to the mechanisms by which HIFU exerts its effects.

Routine screening for pain combined with a pain treatment protocol in head and neck cancer: a randomised controlled trial.

BACKGROUND: We compared the effectiveness and cost of a pain screening and treatment program, with usual care in head and neck cancer patients with significant pain. METHODS: Patients were screened for the presence of pain and then randomly assigned to either an intervention group, consisting of a pain treatment protocol and an education program, or to usual care. Primary outcome was change in the Pain Severity Index (PSI) over three months. RESULTS: We screened 1074 patients of whom 156 were randomized to either intervention or usual care. Mean PSI was reduced over three months in both groups, with no significant difference between the two groups. The Pain Management Index (PMI) at three months, was significantly improved in the intervention group compared with usual care (P<0.001), as was Patient Satisfaction (mean difference in scores was statistically significant: -0.30 [-0.60 to -0.15]). All subjects reported clinically significant levels of anxiety and depression throughout the study. Treatment costs were significantly higher for intervention (mean=£400) compared with usual care (£200), with a low likelihood of being cost-effective. CONCLUSIONS: There was no difference in the Pain Severity Index between the two groups. However there were significant improvements in the intervention group in patient satisfaction and PMI. The pain screening process itself was effective. Sufficient benefit was demonstrated as a result of the intervention to allow continued development of pain treatment pathways, rather than allowing pain treatment to be left to nonformalised ad hoc arrangements.

Establishing sustainable performance-based incentive schemes: views of rural health workers from qualitative research in three sub-Saharan African countries.

INTRODUCTION: Performance-based incentives (PBIs) are currently receiving attention as a strategy for improving the quality of care that health providers deliver. Experiences from several African countries have shown that PBIs can trigger improvements, particularly in the area of maternal and neonatal health. The involvement of health workers in deciding how their performance should be measured is recommended. Only limited information is available about how such schemes can be made sustainable. This study explored the types of PBIs that rural health workers suggested, their ideas regarding the management and sustainability of such schemes, and their views on which indicators best lend themselves to the monitoring of performance. In this article the authors reported the findings from a cross-country survey conducted in Burkina Faso, Ghana and Tanzania. METHODS: The study was exploratory with qualitative methodology. In-depth interviews were conducted with 29 maternal and neonatal healthcare providers, four district health managers and two policy makers (total 35 respondents) from one district in each of the three countries. The respondents were purposively selected from six peripheral health facilities. Care was taken to include providers who had a management role. By also including respondents from district and policy level a comparison of perspectives from different levels of the health system was facilitated. The data that was collected was coded and analysed with support of NVivo v8 software. RESULTS: The most frequently suggested PBIs amongst the respondents in Burkina Faso were training with per-diems, bonuses and recognition of work done. The respondents in Tanzania favoured training with per-diems, as well as payment of overtime, and timely promotion. The respondents in Ghana also called for training, including paid study leave, payment of overtime and recognition schemes for health workers or facilities. Respondents in the three countries supported the mobilisation of local resources to make incentive schemes more sustainable. There was a general view that it was easier to integrate the cost of non-financial incentives in local budgets. There were concerns about the fairness of such schemes from the provider level in all three countries. District managers were worried about the workload that would be required to manage the schemes. The providers themselves were less clear about which indicators best lent themselves to the purpose of performance monitoring. District managers and policy makers most commonly suggested indicators that were in line with national maternal and neonatal healthcare indicators. CONCLUSIONS: The study showed that health workers have considerable interest in performance-based incentive schemes and are concerned about their sustainability. There is a need to further explore the use of non-financial incentives in PBI schemes, as such incentives were considered to stand a greater chance of being integrated into local budgets. Ensuring participation of healthcare providers in the design of such schemes is likely to achieve buy-in and endorsement from the health workers involved. However, input from managers and policy makers is essential to keep expectations realistic and to ensure the indicators selected fit the purpose and are part of routine reporting systems.

Breast-feeding and formula feeding in healthy term infants and bone health at age 10 years.

Few studies have investigated the effects of infant nutrition on later bone health in term infants, although low sn-2 palmitate in infant formulas has been shown to result in the formation of stool fatty acid soaps, reduced Ca absorption and lower bone mass in the short term. To investigate the effect of (1) breast-feeding (BF) and (2) the type of infant formula (standard fat blend v. high-sn-2 fat blend) on bone mass at age 10 years, anthropometry and bone mass (from dual-energy X-ray absorptiometry (GE Lunar Prodigy); lumbar spine (LS) and total body less head; adjusted for size (bone mineral apparent density standard deviation score (SDS) and regression)) were measured in 10-year-old subjects born at term and either breast-fed (n 34) or randomised to a standard control formula (n 27) or a high-sn-2 palmitate formula (n 30) for the first 12 weeks of life. At follow-up, previously BF children were older but lighter (by 0·5 SDS, P= 0·03) than formula-fed children with a lower LS bone mineral density SDS (by 0·44, P= 0·03), but size-adjusted bone mass did not differ. There were no significant differences in bone mass between the formula-fed groups. These findings suggest that there is no significant effect of BF or high-sn-2 infant formula on size-adjusted bone mass in mid-childhood, and that the effects of infant nutrition on bone mass previously reported may be confined to the short term. A larger study would be required to exclude smaller effects.

Human milk oligosaccharides promote the growth of staphylococci.

Human milk oligosaccharides (HMO), which constitute a major component of human milk, promote the growth of particular bacterial species in the infant's gastrointestinal tract. We hypothesized that HMO also interact with the bacterial communities present in human milk. To test this hypothesis, two experiments were conducted. First, milk samples were collected from healthy women (n = 16); culture-independent analysis of the bacterial communities was performed, HMO content was analyzed, and the relation between these factors was investigated. A positive correlation was observed between the relative abundance of Staphylococcus and total HMO content (r = 0.66). In a follow-up study, we conducted a series of in vitro growth curve experiments utilizing Staphylococcus aureus or Staphylococcus epidermidis and HMO isolated from human milk. HMO exhibited stimulatory effects on bacterial growth under various nutritional conditions. Analysis of culture supernatants from these experiments revealed that HMO did not measurably disappear from the culture medium, indicating that the growth-enhancing effects were not a result of bacterial metabolism of the HMO. Instead, stimulation of growth caused greater utilization of amino acids in minimal medium. Collectively, the data provide evidence that HMO may promote the growth of Staphylococcus species in the lactating mammary gland.

Effects of dietary betaine on milk yield and milk composition of mid-lactation Holstein dairy cows.

Betaine, naturally found in plants and an oxidative product of choline, is converted to acetate in the rumen, which may be used for milk fat synthesis. The objective of this study was to determine the effect of supplemental dietary betaine on milk yield and milk composition. Eighteen Holstein dairy cows (126±5 d in milk; mean ± SD) were randomly assigned to a sequence of treatments of rumen-unprotected betaine at 0, 25, 50, and 100 g/d added to a standard lactation ration in a 4×4 Latin square design. Animals were fed individually with feed intake and milk yield recorded daily. Body condition score and body weight were recorded on the last day of each period that lasted 16 d, with milk sampled on the last 2 d of each period. Milk composition was determined by a Dairy Herd Improvement Association laboratory and milk fatty acids were determined by gas chromatography. Data collected over the last 2 to 3 d were analyzed using the MIXED procedure in SAS (SAS Institute Inc., Cary, NC). Milk yield (mean ± SEM) was increased by betaine when fed at 100g/d (22.4, 22.5, 22.8, 24.1±1.19 kg/d for 0, 25, 50, and 100g of betaine/d, respectively). No effect of dietary betaine was detected on dry matter intake, feed efficiency, body weight, or body condition score. Percentages of milk fat, lactose, solids-not-fat, and somatic cell count were not altered; however, protein concentration was decreased by betaine supplementation as compared with the control (3.35, 3.28, 3.27, and 3.28±0.07% for 0, 25, 50, and 100 g of betaine/d, respectively). Daily yields of milk protein, fat, lactose, energy-corrected milk, and 3.5% fat-corrected milk did not differ with betaine supplementation. Overall, inclusion of dietary betaine at 100 g/d increased milk yield, whereas all levels of betaine supplementation decreased milk protein percent and slightly altered milk fatty acid profile. Further studies are needed to determine the ruminal fermentation characteristics and the optimum rate of supplemental betaine for dairy cows.

Prenatal and postnatal programming of body composition in obese children and adolescents: evidence from anthropometry, DXA and the 4-component model.

BACKGROUND: Low-birth weight has been proposed to programme central adiposity in childhood. However, there is little information on associations between fetal weight gain and fat distribution within obese individuals. OBJECTIVES: To investigate associations between birth weight and postnatal weight gain with body composition in a sample of obese children and adolescents. SUBJECTS AND METHODS: Body composition was measured using anthropometry, dual-emission X-ray absorptiometry and the 4-component model in 45 male and 76 female obese individuals aged 5-22 years. General linear models were used to investigate associations between birth weight standard deviation score (SDS), or change in weight SDS between birth and follow-up, and body composition, adjusting for age, pubertal status, height and gender. RESULTS: Birth weight SDS ranged from -1.86 to 3.46, and was inversely associated with current weight SDS after adjustment for height SDS. Birth weight SDS was weakly associated with waist and hip girths, but not waist-hip ratio or trunk fat, after adjusting for age, height, pubertal status and gender. Change in weight SDS was strongly associated with total and central adiposity. CONCLUSIONS: Despite incorporating substantial variability, birth weight SDS was only a weak predictor of tissue masses and their distribution in obese children. Variability in central adiposity was more strongly associated with the magnitude of postnatal growth, which in turn was weakly inversely associated with birth weight SDS. In a population uniformly characterised by excess body weight, postnatal weight gain exerted the dominant impact on adiposity and fat distribution.

The prevalence of pain in patients attending sarcoma outpatient clinics.

The prevalence of pain in patients with sarcoma is not well documented. We investigated this in outpatients at a tertiary cancer referral centre, assessing the adequacy of pain control and for risk factors leading to higher prevalence and severity of pain. 149 patients were surveyed. Patients with pain within the previous 7 days completed pain assessment tools (BPI, S-LANSS, PMI). 53% of patients had pain within the previous 7 days, and 25% had significant pain. Of those with pain, 63% was inadequately controlled and neuropathic pain was identified in 36%. Age, gender, tumour type, and the type of cancer treatment were not significant predictors of the prevalence or severity of the pain. Based on our results, patients with sarcoma should be actively screened for pain and have regular reviews of their analgesic requirements.

MR Imaging Characteristics of Intraocular Perfluoro-n-Octane.

We describe the unique MR imaging characteristics of intraocular perfluoro-n-octane, a liquid used for intraoperative and postoperative tamponade in the context of complex retinal detachment repair, and contrast it with other intraocular pathologies. Because trace amounts of perfluoro-n-octane may be left in the globe postoperatively, it may be confused for other abnormalities, such as foreign bodies or tumors.

Evaluation of DXA against the four-component model of body composition in obese children and adolescents aged 5-21 years.

BACKGROUND: Body composition is increasingly measured in pediatric obese patients. Although dual-energy X-ray absorptiometry (DXA) is widely available, and is precise, its accuracy for body composition assessment in obese children remains untested. OBJECTIVE: We aimed to evaluate DXA against the four-component (4C) model in obese children and adolescents in both cross-sectional and longitudinal contexts. DESIGN: Body composition was measured by DXA (Lunar Prodigy) and the 4C model in 174 obese individuals aged 5-21 years, of whom 66 had a second measurement within 1.4 years. The Bland-Altman method was used to assess agreement between techniques for baseline body composition and change therein. RESULTS: A significant minority of individuals (n=21) could not be scanned successfully due to their large size. At baseline, in 153 individuals with complete data, DXA significantly overestimated fat mass (FM; Delta=0.9, s.d. 2.1 kg, P<0.0001) and underestimated lean mass (LM; Delta=-1.0, s.d. 2.1 kg, P<0.0001). Multiple regression analysis showed that gender, puberty status, LM and FM were associated with the magnitude of the bias. In the longitudinal study of 51 individuals, the mean bias in change in fat or LM did not differ significantly from zero (FM: Delta=-0.02, P=0.9; LM: Delta=0.04, P=0.8), however limits of agreement were wide (FM: +/-3.2 kg; LM: +/-3.0 kg). The proportion of variance in the reference values explained by DXA was 76% for change in FM and 43% for change in LM. CONCLUSIONS: There are limitations to the accuracy of DXA using Lunar Prodigy for assessing body composition or changes therein in obese children. The causes of differential bias include variability in the magnitude of tissue masses, and stage of pubertal development. Further work is required to evaluate this scenario for other DXA models and manufacturers.

Mid-IR laser oscillation in Cr2+:ZnSe planar waveguide.

We demonstrate 2.6 µm mid-infrared lasing at room temperature in a planar waveguide structure. Planar waveguides were fabricated using pulsed laser deposition (PLD) by depositing chromium doped zinc selenide thin films on sapphire substrate (Cr2+:ZnSe/sapphire). Highly doped Cr2+:ZnSe/Sapphire thin film sample was also used to demonstrate passive Q-switching of Er:YAG laser operating at 1.645 µm.

Modulation of the metastatic activity of melanoma cells by laminin and fibronectin.

Metastatic mouse melanoma cells have a high affinity for the basement membrane and the ability to degrade it; these properties may allow tumor cells to invade the membrane and disseminate. In this study it was found that the metastatic potential of mouse melanoma cells varied when the cells were exposed in culture to fibronectin or laminin. After removal of fibronectin or exposure to laminin, the cells had an increased affinity for basement membrane collagen, were more invasive of basement membranes in vitro, and produced more lung colonies in vivo. These changes are correlated with and may be due to an increase in the laminin-binding capacity of the tumor cell surface.

Variation in injury risk over the course of a two-day youth club soccer tournament.

Athletic injury risk in youth is known to be greater in organised sport, higher levels of competition, games, and tournaments, yet young athletes are often expected to participate in tournaments that involve multiple matches per day on consecutive days. In 2006 and 2008 injury rates were observed during a club youth soccer tournament that involved athletes aged 9-18 years playing three to four matches over two consecutive days, to determine if injury risk varied over the course of the event. The injury rate for day 1 was 7.91/1000 hours with a mean severity of 3.5 days missed versus a day 2 rate of 6.75 and severity of 2.3. The rate and severity for the first game in a day were 7.13 and 3.5 respectively compared to 7.9 and 2.5 for game 2. Further research is needed to determine if a high density match schedule increases injury risk for youth soccer players.

Bioelectric impedance vector analysis (BIVA) in hospitalised children; predictors and associations with clinical outcomes.

BACKGROUND: Clinical use of bioelectric impedance is limited by variability in hydration. Analysis of raw bioelectric impedance vectors (BIVA), resistance (R), reactance (Xc) and phase angle (PA) may be an alternative for monitoring disease progression/treatment. Clinical experience of BIVA in children is limited. We investigated predictors of BIVA and their ability to predict clinical outcomes in children with complex diagnoses. METHODS: R, Xc and PA were measured (BODYSTAT Quadscan 4000) on admission in 108 patients (4.6-16.8 years, mean 10.0). R and Xc were indexed by height (H) and BIVA-SDS for age and sex calculated using data from healthy children. Potential predictors and clinical outcomes (greater-than-expected length-of-stay (LOS), complications) were recorded. RESULTS: Mean R/H-SDS was significantly higher (0.99 (SD 1.32)) and PA-SDS lower (-1.22 (1.68))) than expected, with a wide range for all parameters. In multivariate models, the Strongkids risk category predicted R/H-SDS (adjusted mean for low, medium and high risk = 0.49, 1.28, 2.17, p = 0.009) and PA-SDS (adjusted mean -0.52, -1.53, -2.36, p = 0.01). BIVA-SDS were not significantly different in patients with or without adverse outcomes. CONCLUSIONS: These complex patients had abnormal mean BIVA-SDS suggestive of reduced hydration and poor cellular health according to conventional interpretation. R/H-SDS was higher and PA-SDS lower in those classified as higher malnutrition risk by the StrongKids tool. Further investigation in specific patient groups, including those with acute fluid shifts and using disease-specific outcomes, may better define the clinical role of BIV.

Reduction in bone mineral density in glycogenosis type III may be due to a mixed muscle and bone deficit.

UNLABELLED: Glycogen storage disease type III (GSD III; OMIM 232400) is an autosomal recessive deficiency of the glycogen debrancher enzyme, amylo-1,6-glucosidase (EC 3.2.1.33). Patients with other hepatic glycogenoses are known to have reduced bone mineral content (BMC) and to be at consequent risk of fractures. They have key metabolic differences from GSD III patients, however. This study examines bone density and metabolism in 15 GSD III patients (6 female) from childhood to adulthood (aged 10-34 years). The results demonstrate that patients with GSD III have low bone mass at all skeletal sites compared with healthy individuals of the same age and sex, with a significant proportion (40-64%) having BMD > 2 standard deviations below the mean for whole body and lumbar spine. The deficiency seems to be attributable to a mixed muscle andbone deficit. Lower bone mass was found at all sites for GSD IIIa patients (combined liver and muscle defect) compared with GSD IIIb patients (liver only defect). CONCLUSION: Patients with GSD III have significantly abnormal bone mass, placing them at increased risk of potential fracture. The underlying mechanism is probably multifactorial with contributions from abnormal muscle physiology, abnormal metabolic milieu and altered nutrition affecting micronutrient intake. Therapies need to address all these factors to be successful.

Undercarboxylated osteocalcin and bone mass in 8-12 year old children with cystic fibrosis.

UNLABELLED: Young adults with cystic fibrosis (CF) frequently develop bone disease. One suggested aetiological factor is suboptimal vitamin K status with impaired carboxylation of osteocalcin and abnormal bone formation. METHODS: We measured bone mineralization and turnover in thirty-two 8-12 year old CF patients (14 boys) using Dual Energy X-ray absorptiometry (whole body (WB) and lumbar spine (LS)), 25-OH Vitamin D, PTH and markers of bone formation (plasma osteocalcin, N-terminal pro-peptide of type 1 collagen (P1NP)), plus an indirect measure of vitamin K status, undercarboxylated osteocalcin (uc-OC). RESULTS: LS bone mineral density (BMD) standard deviation (SD) scores were < -1.0 in 20% of subjects. Size-adjusted LS and WB bone mass was normal. Compared to reference data, % uc-OC was high and P1NP low. LS bone mass was predicted by % uc-OC but not other markers (0.4% decrease in size-adjusted LSBMC (p=0.05); 0.04 SD decrease in LSBMAD (p=0.04) per 1% increase in uc-OC). CONCLUSION: Markers suggestive of sub-optimal vitamin K status and low bone formation were present despite normal size-adjusted bone mass. The association between LSBMC and % uc-OC is consistent with the hypothesis that sub-optimal vitamin K status is a risk factor for CF bone disease. This should ideally be investigated in an intervention trial.

Engaging recreational fishers in management and conservation: global case studies.

Globally, the number of recreational fishers is sizeable and increasing in many countries. Associated with this trend is the potential for negative impacts on fish stocks through exploitation or management measures such as stocking and introduction of non-native fishes. Nevertheless, recreational fishers can be instrumental in successful fisheries conservation through active involvement in, or initiation of, conservation projects to reduce both direct and external stressors contributing to fishery declines. Understanding fishers' concerns for sustained access to the resource and developing methods for their meaningful participation can have positive impacts on conservation efforts. We examined a suite of case studies that demonstrate successful involvement of recreational fishers in conservation and management activities that span developed and developing countries, temperate and tropical regions, marine and freshwater systems, and open- and closed-access fisheries. To illustrate potential benefits and challenges of involving recreational fishers in fisheries management and conservation, we examined the socioeconomic and ecological contexts of each case study. We devised a conceptual framework for the engagement of recreational fishers that targets particular types of involvement (enforcement, advocacy, conservation, management design [type and location], research, and monitoring) on the basis of degree of stakeholder stewardship, scale of the fishery, and source of impacts (internal or external). These activities can be enhanced by incorporating local knowledge and traditions, taking advantage of leadership and regional networks, and creating collaborations among various stakeholder groups, scientists, and agencies to maximize the probability of recreational fisher involvement and project success.

Laminin molecular domains which alter metastasis in a murine model.

Human and murine tumor cells contain cell surface receptors for the basement membrane glycoprotein laminin. Since a biologic role for the receptor had not previously been demonstrated, we explored the possibility that the laminin receptor may be involved in hematogenous metastases formation. Preincubation of metastatic murine melanoma cells with syngeneic whole laminin followed by tail vein injection increased tumor cell retention in the lung and strongly stimulated metastases formation. The domain of the laminin molecule responsible for stimulating metastases was identified. Laminin is a cross-shaped molecule with three short arms and one long arm. All arms have globular end regions. Purified protease-derived fragments of laminin were prepared which (a) lacked only the long arm of the molecule (alpha fragment) or, (b) lacked both the long arm and the globular end regions of the short arms (C1 fragment). Both types of fragments contained the laminin receptor binding region. The fragments had opposite effects on metastases. The alpha fragment stimulated metastases formation to the same extent as whole laminin. In contrast, the C1 fragment greatly reduced or abolished metastases formation in a dose-dependent manner. The C1 fragment also inhibited tumor cell attachment to whole amnion basement membrane in vitro. We conclude that intact globular end regions on the short arms (but not the long arm) of the cell surface receptor-bound laminin molecule are necessary for stimulating metastases by the intravenous route.