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Rectal cancer is a common cancer, with presently a 5-year survival of 67 %. Treatment is based on tumor stage, but current staging methods, such as magnetic resonance imaging (MRI) or ultrasound, are limited in the ability to correctly stage the disease. Magnetomotive ultrasound is a developing modality that has a potential to improve rectal cancer staging. Magnetic nanoparticles are set in motion by an external magnetic field, and the resulting motion signature is detected by ultrasound. Here, we report on magnetomotive images of magnetic nanoparticles in human tissue, using a prototype system where a rotating permanent magnet provides the varying magnetic field, and an ultrasound transducer array encircling the magnet, detects the induced motion. Prior to surgery, a patient with a low rectal tumor was injected at three sites close to the tumor with magnetic nanoparticles. Postsurgical magnetomotive ultrasound scanning revealed the three injection sites, with no obvious artefactual signals. A phantom study showed detection of nanoparticles beyond 40 mm, where 30 mm is the expected maximum distance to mesorectal lymph nodes. Magnetomotive ultrasound image of iron oxide nanoparticles in human tissue. Prior to surgery a patient was injected with nanoparticles, and the excised tissue specimen was imaged with a prototype magnetomotive ultrasound system. The three colored areas overlaid on the standard B-mode greyscale image, correspond to the three injection sites., Competing Interests: Declaration of competing interest TJ owns shares in Nanoecho AB (3.33 %) and holds a seat on the company board; LJ and AM are full time employees at Nanoecho AB, and each own shares in the company (<1 %); LP is the CEO of Nanoecho AB and owns shares in the company (<1 %), EA declares no conflict of interest., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: To achieve reference values for computerized strain-gauge plethysmography (SGP), to assess reproducibility, and to evaluate the influence of different factors such as age, gender, body mass index, and symptomatic post-thrombotic disease on commonly used variables., Methods: Sixty-three healthy controls and 56 patients with previous deep venous thrombosis (DVT) were included. All participants underwent computerized SGP with evaluation of outflow capacity, as well as evaluation of venous reflux and muscle pump function., Results: All variables were significantly reduced in DVT limbs, both compared with contralateral limbs and with healthy controls. Only two patients had all values within normal ranges (=mean ± 2 SD in controls). Measures of outflow capacity had a coefficient of variation (CV) of 5-6% and exercise-induced volume changes a CV of 10-15%. In symptomatic post-thrombotic limbs half-refilling time was significantly related to presence of edema (R = -0.28, p < .05) and to chronic skin changes (R = -0.58, p < .001)., Conclusions: We suggest that our values in healthy controls can be used as new reference values for computerized venous strain-gauge plethysmography. The computerized design ensures high reproducibility and the results indicate that this is a very useful and sensitive test for functional quantitative assessment of patients with venous disease., (Copyright © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.)

Nanometer scale surface features on implants and prostheses can potentially be used to enhance osseointegration and may also add further functionalities, such as infection resistance, to the implant. In this study, a nanostructured noble metal coating consisting of palladium, gold and silver, never previously used in bone applications, was applied to machined titanium screws to evaluate osseointegration after 6 and 12 weeks in rabbit tibiae and femurs. Infection resistance was confirmed by in vitro adhesion test. A qualitatively and quantitatively similar in vivo bone response was observed for the coated and uncoated control screws, using histology, histomorphometry and electron microscopy. The bone-implant interface analysis revealed an extensive bone formation and direct bone-implant contact. These results demonstrate that the nanostructured noble metal coating with antimicrobial properties promotes osseointegration and may therefore be used to add extra implant functionality in the form of increased resistance to infection without the use of antibiotics., From the Clinical Editor: The authors of this paper demonstrate that nanostructured noble metal coating of implants and prostheses used in orthopedic procedures promotes osseointegration and may be used to add extra implant functionality in the form of increased resistance to infection without the use of antibiotics., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Organic chemicals may be released when consumer goods are used, contributing to environmental and human levels of potentially hazardous chemicals. A generic model was developed to predict emissions of organic chemicals from various materials in consumer products. The model involved three modules, which each predict a key parameter needed to calculate the mass of individual chemicals emitted. Partition coefficients between a material and the surrounding air were predicted using Abraham solvation parameters, diffusion coefficients in materials were calculated using the Piringer equation, and convective mass transfer coefficients were evaluated by applying the Chilton-Colburn analogy. The calculated emission rates from predicted parameters were evaluated and agreed well with literature data. The release of plasticizers from vinyl flooring used in Sweden was calculated to demonstrate the utility of the generic model. The estimated emitted masses of di(2-ethylhexyl)phthalate (DEHP), di-iso-nonylphthalate (DINP), and 1,2-cyclohexanedicarboxylic acid di-iso-nonyl ester (DINCH) in 2012 were 210 kg, 40 kg, and 3.6 kg respectively. Emissions from vinyl flooring were estimated for the period 1990 to 2035 and it was shown that the recent substitution of DEHP with DINP will help to reduce plasticizer emissions. Model calculations for alternative plasticizers revealed that DINCH would yield similar emissions to DINP, whereas use of diethyl hexyl-iso-sorbide or diethyl hexyl adipate would result in higher emissions., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Replacing SFAs with vegetable PUFAs has cardiometabolic benefits, but the effects on liver fat are unknown. Increased dietary n-6 PUFAs have, however, also been proposed to promote inflammation-a yet unproven theory., Objective: We investigated the effects of PUFAs on liver fat, systemic inflammation, and metabolic disorders., Design: We randomly assigned 67 abdominally obese subjects (15% had type 2 diabetes) to a 10-wk isocaloric diet high in vegetable n-6 PUFA (PUFA diet) or SFA mainly from butter (SFA diet), without altering the macronutrient intake. Liver fat was assessed by MRI and magnetic resonance proton (1H) spectroscopy (MRS). Proprotein convertase subtilisin/kexin type-9 (PCSK9, a hepatic LDL-receptor regulator), inflammation, and adipose tissue expression of inflammatory and lipogenic genes were determined., Results: A total of 61 subjects completed the study. Body weight modestly increased but was not different between groups. Liver fat was lower during the PUFA diet than during the SFA diet [between-group difference in relative change from baseline; 16% (MRI; P < 0.001), 34% (MRS; P = 0.02)]. PCSK9 (P = 0.001), TNF receptor-2 (P < 0.01), and IL-1 receptor antagonist (P = 0.02) concentrations were lower during the PUFA diet, whereas insulin (P = 0.06) tended to be higher during the SFA diet. In compliant subjects (defined as change in serum linoleic acid), insulin, total/HDL-cholesterol ratio, LDL cholesterol, and triglycerides were lower during the PUFA diet than during the SFA diet (P < 0.05). Adipose tissue gene expression was unchanged., Conclusions: Compared with SFA intake, n-6 PUFAs reduce liver fat and modestly improve metabolic status, without weight loss. A high n-6 PUFA intake does not cause any signs of inflammation or oxidative stress. Downregulation of PCSK9 could be a novel mechanism behind the cholesterol-lowering effects of PUFAs. This trial was registered at clinicaltrials.gov as NCT01038102.

A vibrational spectroscopy study (infrared and Raman) is reported for the biogenic polyamine analogues norspermidine (NSpd), N(1),N(11)-bis(ethyl)norspermine (BENSpm) and N(1)-cyclo-propylmethyl-N(11)-ethylnorspermine (CPENSpm), as well as for their newly synthesised Pt(II) and Pd(II) complexes. Attending to the potential antineoplastic properties of this kind of systems, their full conformational characterization is essential for understanding the molecular basis of their cytotoxic activity and the mechanisms through which they are transported into the cell. The all-trans geometry was found to be favoured for all the alkylated polyamines, in their totally protonated state, while their polynuclear complexes presented a stable geometry very similar to that previously obtained for the analogous chelates with spermidine (M(3)Spd(2)) and spermine (M(2)Spm), comprising two or three cisplatin-like (MCl(2)NH(2)) moieties., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A human skull with mandible from the Ngada District on the island of Flores, Indonesia, is described in order to contribute to the knowledge of variation in cranial architecture, which is important in interpretations of evolutionary cerebralisation. The skull was excavated in 1924 and sent to the National Museum in Copenhagen. The "Copenhagen Flores" (CF) male skull is radiocarbon-dated and of modern age. The cranium is small, but larger than e.g. Liang Bua skull (LB1) in every measurement. The (CT-scan based) cranial capacity of 1258 ml is normal for modern humans, but somewhat lower than values from the middle or upper Palaeolithics. The metric cranial data analysed in FORDISC, characterize the skull as a male Vietnamese rather than a Chinese or White individual. Tooth morphology shows the sundadont pattern and tooth size corresponds to that of teeth from Bali, Java and Malayan Orang Asli. Remarkable are the marked asymmetries in the dentition with rotation of an upper premolar and congenital absence of a third molar. In these respects the CF skull is similar to dentitions belonging to the pygmoid villagers of Rampasasa, a village not far from the Liang Bua cave, and to LB1., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

Background: Deep venous thrombosis (DVT) occurs frequently in patients undergoing orthopedic surgery, but there is a lack of knowledge regarding long-term sequelae of DVT after different types of surgical procedures., Objective: To describe the long-term effect of symptomatic (SDVT) and asymptomatic (ADVT) deep venous thrombosis on venous function and subsequent incidence of post-thrombotic syndrome (PTS) in patients who have undergone surgery for Achilles tendon rupture., Patients/methods: This observational follow-up study includes 83 patients with postoperative DVT, examined after a mean of 7 years. There were two series of patients: 45 with SDVT and 38 with ADVT. In both series, more than 90% of the DVTs were limited to calf veins. Follow-up examinations comprised color duplex ultrasonography (CDU), strain-gauge plethysmography (SGP), clinical examination including scoring for venous disease and questionnaires for quality of life (QOL)., Results: A mild degree of PTS was found in 11% of the patients: 13% in SDVT and 8% in ADVT patients. The rate of recurrent ipsilateral DVT was 2%. Deep venous reflux was more common in patients with SDVT than in ADVT patients (84% vs. 55%, P < 0.01). Only a few patients had plethysmograpically abnormal findings without difference between the two groups., Conclusion: DVT after surgery for Achilles tendon rupture consists mainly of distal DVTs and are associated with a low risk for PTS. Deep venous reflux was more common in SDVT than in ADVT patients, probably as an effect of larger DVTs in the former group., (© 2011 International Society on Thrombosis and Haemostasis.)

This study investigated the effect of mechanical infection control for periodontitis and periodontal surgery on the prevalence of well-established risk factors for atherosclerosis, and plasma levels of cytokines, antibodies against heat shock proteins and markers of systemic inflammation. Sixty-eight patients between 39 and 73 years of age with severe periodontitis who had been referred to four specialist periodontology clinics in Sweden were investigated. A fasting venous blood sample was taken at baseline and additional samples were collected after 3 and 12 months. A total of 54 patients underwent periodontal treatment. The periodontal treatment was successful, as pathogenic gingival pockets decreased significantly. Plasma glucose, lipids and markers of systemic inflammation were not significantly altered after 3 months. One year after the initial treatment, HDL-C concentrations were significantly increased (Delta0.08mmol/L) whereas LDL-C concentrations decreased (Delta0.23mmol/L). Haptoglobin concentrations were also lower. Interleukin-18 and interferon-gamma levels were also lower after 12 months (60ng/L (-23%) and 11ng/L (-97%) respectively). Treatment had no effect on plasma levels of IgA, IgG1, IgG2 antibodies against heat shock proteins. In conclusion, this study indicates that standard treatment for periodontal disease induces systemic changes in several biochemical markers that reflect the risk for atherosclerosis.

Unlabelled: Post-thrombotic syndrome (PTS) is a well-recognized condition that develops after symptomatic deep venous thrombosis, but the clinical significance and late complications of asymptomatic deep venous thrombosis (ADVT) are unclear., Objective: To determine whether ADVT following minor surgery affects venous function and contributes to the later development of PTS., Patients/methods: The study included 83 patients operated on for Achilles tendon rupture; 38 patients with postoperative ADVT and 45 patients without (control group). The follow-up examinations five years after the operation comprised computerised strain-gauge plethysmography, colour duplex ultrasonography, clinical scoring of venous disease, and quality of life (QOL)., Results: Villalta scores, CEAP classification and QOL did not differ between groups. PTS (=Villalta score > or =5) was found in three ADVT patients (8%) and in two controls (4%). Ultrasonography revealed post-thrombotic changes in 55% of ADVT patients and in none of the controls. Deep venous reflux occurred in 22 ADVT patients and in three controls (P<0.001). There was no difference between groups in plethysmographic variables, demonstrating that the ultrasonographic abnormalities were of negligible haemodynamic significance., Conclusions: PTS is not a common sequel to ADVT after minor surgery. Although more than 50% of patients with ADVT developed post-thrombotic changes according to ultrasound, these changes did not result in haemodynamically significant venous dysfunction.

The amphipod crustacean Talitrus saltator is an established, easily accessible, biomonitor of trace metal bioavailabilities in coastal waters. We have carried out a geographically widespread collection of T. saltator from European shores, stretching from the north-west Atlantic through the Baltic to the Mediterranean. A primary aim of the work was to establish a database of accumulated trace metal concentrations (Cd, Cr, Cu, Fe, Mn and Zn) in this biomonitor. Statistical analysis has shown significant geographical differences in the bioavailabilities of all the metals, the most distinct being copper, iron and manganese. It has proved possible to identify unusually high accumulated concentrations of Cd, Cr, Cu, Fe, Mn and Zn in this biomonitor, indicative of high metal bioavailability at a particular site. These may serve as reference points for future biomonitoring programmes seeking to identify metal contamination in coastal waters.

Many animal species live in groups. Group living may increase exploitation competition within the group, and variation among groups in intra-group competition intensity could induce life-history variability among groups. Models of physiologically structured populations generally predict single generation cycles, driven by exploitation competition within and between generations. We expect that life-history variability and habitat heterogeneity induced by group living may affect such competition-driven population dynamics. In this study, we vary the gregariousness (the tendency to aggregate in groups) of a size-structured consumer population in a spatially explicit environment. The consumer has limited mobility, and moves according to a probabilistic movement process. We study the effects on the population dynamics, as mediated through the resource and the life-history of the consumer. We find that high gregariousness leads to large spatial resource variation, and highly variable individual life-history, resulting in highly stochastic population dynamics. At reduced gregariousness, life-history of consumers synchronizes, habitat heterogeneity is reduced, and single generation cycles appear. We expect this pattern to occur for any group living organism with limited mobility. Our results indicate that constraints set by population dynamical feedback may be an important aspect in understanding group living in nature.

The polyamines are essential for cellular growth and differentiation. Ornithine decarboxylase (ODC), which catalyses the first step in the biosynthesis of the polyamines, has a very fast turnover and is subject to a strong feedback control by the polyamines. In the present study, we show that overexpression of a metabolically stable ODC in CHO cells induced a massive cell death unless the cells were grown in the presence of the ODC inhibitor alpha-difluoromethylornithine (DFMO). Cells overexpressing wild-type (unstable) ODC, on the other hand, were not dependent on the presence of DFMO for their growth. The induction of cell death was correlated with a dramatic increase in cellular putrescine levels. Analysis using flow cytometry revealed perturbed cell cycle kinetics, with a large accumulation of cells with sub-G1 amounts of DNA, which is a typical sign of apoptosis. Another strong indication of apoptosis was the finding that one of the key enzymes in the apoptotic process, caspase-3, was induced when DFMO was omitted from the growth medium. Furthermore, inhibition of the caspase activity significantly reduced the recruitment of cells to the sub-G1 fraction. In conclusion, deregulation of polyamine homeostasis may negatively affect cell proliferation and eventually lead to cell death by apoptosis if putrescine levels become too high.

The Allee effect, a reduction of individual fitness at low population density that can lead to sudden and unannounced extinctions, has been shown to come about through a number of mechanisms, usually associated with group behavior or mate search. Recent papers show that it may arise through size-selective predation, without explicit assumptions relating individual fitness to population density. It arises from the shift that a predator induces in the population stage distribution of its prey. We study the parameter conditions that lead to such an emergent Allee effect. The emergent Allee effect occurs under fairly broad conditions. We show that stage-specific predation can also induce bistability between alternative states where both prey and predator are present. A perturbation analysis on the equilibria shows that all equilibria are highly robust to changes in predator density. Our work shows that when size-specific interactions are taken into account, bistabilities and catastrophic collapses are possible even in purely exploitative food webs, which has substantial implications for questions related to food web theory and conservation issues.

Background: Iron and zinc deficiency are prevalent during infancy in low-income countries., Objectives: The objectives were to examine whether a weekly supplement of iron, zinc, iron+zinc, or a micronutrient mix (MM) of 16 vitamins and minerals would alter infant development and behavior., Design: The participants were 221 infants from rural Bangladesh at risk of micronutrient deficiencies. Development and behavior were evaluated at 6 and 12 mo of age by using the Bayley Scales of Infant Development II and the Home Observation Measurement of Environment (HOME) scale. In this double-blind trial, the infants were randomly assigned to 1 of 5 treatment conditions: iron (20 mg), zinc (20 mg), iron+zinc, MM (16 vitamins and minerals, including iron and zinc), or riboflavin weekly from 6 to 12 mo. Multivariate analyses were conducted to examine the change in development and behavior for each supplementation group, with control for maternal education, HOME score, months breastfed, anemia, growth at 6 mo, and change in growth from 6 to 12 mo., Results: Iron and zinc administered together and with other micronutrients had a beneficial effect on infant motor development. Iron and zinc administered individually and in combination had a beneficial effect on orientation-engagement. Two-thirds of the infants were mildly anemic, no treatment effects on hemoglobin concentration were observed, and hemoglobin was not associated with measures of development or behavior., Conclusion: The beneficial effects of weekly iron and zinc supplementation on motor development and orientation-engagement suggest that infants benefit from these minerals when administered together.

Objective: To investigate the appearance of cytomegalovirus (CMV) DNA, human herpesvirus-6 (HHV-6) DNA and human herpesvirus-7 (HHV-7) DNA in plasma as a sign of reactivation and possible causes of fever of unknown origin (FUO) during neutropenia., Methods: From 134 patients with febrile neutropenia following cytotoxic chemotherapy during the years 1996-2000, 20 severely neutropenic patients (granulocyte count < 0.1 x 109/L) were selected. Ten were patients with bacteremia and ten were patients with FUO. Five samples from each patient were selected at the start of chemotherapy, at the time of blood culture and fever, after 24 and 48 hours of fever, and, finally, after two to three days without fever. Virus DNA was detected by real-time quantitative and nested polymerase chain reaction (PCR)., Results: CMV-DNA was detected in two out of ten FUO-patients in all samples drawn during fever. From another FUO and during two bacteremia episodes, CMV-DNA was detected after 48 hours of fever. DNA from HHV-6 and HHV-7 was not detected in any of the 20 febrile episodes., Conclusions: HHV-6 and HHV-7 as a possible explanation for FUO in severely neutropenic patients treated with cytotoxic chemotherapy seems not be very likely. However, CMV was identified in 5/20 patients and the febrile episodes in the two FUO-patients with constant DNA-emia may have been caused by a reactivation of CMV. This implies that CMV infection can be expected not only in transplant patients but also in chemotherapy-treated neutropenic patients.

Coeliac disease, also called permanent gluten sensitive enteropathy, has recently been recognised as constituting a widespread health problem. Effective treatment involves the strict exclusion of wheat, rye, barley and possibly also oats from the diet. Genetic susceptibility and the presence of gluten in the diet are prerequisites for developing the disease. Sweden has recently experienced an epidemic of coeliac disease in children below 2 years of age. Previously, considerable changes in incidence over time have also been reported from England, Scotland and Ireland. Such obvious changes in incidence over rather short time periods, in genetically stable populations, emphasise the importance of environmental factors in the aetiology. Thus, most likely, the aetiology of coeliac disease is multifactorial. However, further conclusive evidence is required to settle if environmental factors, beyond presence of gluten in the diet, really influence the immunological process resulting in the coeliac small intestinal lesion, or merely influence the clinical expression of the disease. The search for contributing exposures has thus far focused on early feeding, suggesting that breast-feeding duration and the amount of gluten consumed are of importance, and possibly also the age for introducing gluten into the diet of infants. The pattern of causation may vary over time and between countries, however, which may obscure the search for risk factors. Nevertheless, a challenging possibility that needs to be explored is if coeliac disease can be delayed, or possibly even prevented for an entire life span, by favourable dietary habits.

Objectives: to evaluate clinical and functional long-term outcomes following pregnancy-related medically treated iliofemoral deep venous thrombosis (DVT)., Design: retrospective follow-up of patients identified through a registry search., Material and Methods: twenty-five women underwent clinical examination, colour duplex ultrasound and computerised strain-gauge plethysmography on two occasions a mean of nine and 16 years after DVT., Results: 40% of the patients were completely asymptomatic and 52% had no clinical signs of venous disease after a mean follow-up of 16 years. The clinical signs were in general mild, and none of the 25 patients had skin changes or ulcers. Deep venous reflux was found in 36% of the patients; the same percentage at nine- and 16-years follow-up, and 24% had normal ultrasonographic appearance of all deep veins. None of the patients had plethysmographic evidence of outflow obstruction. There was a significant relationship between measures of venous reflux and the presence of leg swelling, but there was no clear relation between functional abnormalities and the extent of the initial DVT., Conclusion: even after 16 years there are relatively mild symptoms and signs of venous disease in women with medically treated pregnancy-related iliofemoral DVT. Our results do not support earlier stated opinions that these patients represent a particular risk group for developing post-thrombotic syndrome., (Copyright 2001 Harcourt Publishers Limited.)

Amino acid deprivation can inhibit tumour cell proliferation. Since polyamines are required for cell growth, we hypothesised that their regulatory pathways can respond to amino acid restriction. We report here that exposure of human colon adenocarcinoma Caco-2 cells to a medium restricted for a single amino acid, but not for D-glucose, activates spermidine transport. The increase was rapid and seemed transient with a maximum 4-6 hr after amino acid removal. Kinetics showed that the maximal velocity of transport was solely increased in L-methionine- or L-leucine-deprived cells, indicating increased number of transporters. The intracellular level of complex of ornithine decarboxylase (ODC) with antizyme, a negative regulator of polyamine transport, was decreased by 16-29% in amino acid-deprived cells. However, exposure to limited amounts of amino acid increased transport without altering the ODC-antizyme complex level. We propose that antizyme-independent mechanisms, sensitive to the amino acid concentration, also participate to the control of spermidine transport., (Copyright 1999 Academic Press.)

The validity of the Swedish SF-36 Health Survey was examined, replicating techniques used in the U.S. validation. Principal components analysis was used to test the internal structure of the eight SF-36 scales in relation to hypothesized associations with the two major dimensions of health--physical and mental. Hypothesized relationships between scales and external criteria were also examined by means of clinical group contrasts. Both the principal components analysis and clinical group contrasts largely replicated U.S. findings, which supported the cross-cultural stability of the SF-36 in Sweden. As expected, the Physical Functioning and Mental Health scales were most sensitive to clinical manifestations of medical and mental health, respectively. The General Health scale was associated more with physical than mental health. However, the Social Functioning scale and particularly the Vitality scale were more related to mental health in Sweden than in the corresponding U.S. study. Cultural differences and variation in study samples and selection criteria were suggested as possible explanatory factors for these differences.

Histidine decarboxylase catalyses the formation of histamine, an important biological messenger. In spite of the essential biological functions exerted by histamine the knowledge about the mechanisms involved in the regulation of histidine decarboxylase is rather limited. This is most likely due to the limited supply of suitable tools, including highly specific antibodies. In the present study we describe the production and characterisation of specific antisera against rat histidine decarboxylase using recombinant protein synthesised in a bacterial expression system. The antisera were shown to effectively immunoprecipitate histidine decarboxylase activity in extracts of fetal rat liver as well as to detect the histidine decarboxylase protein by Western blot analysis of COS-7 cells expressing recombinant rat histidine decarboxylase. The results demonstrate the successful production of highly specific antisera to histidine decarboxylase which may become valuable tools in future studies of the structure and function of this enzyme.

Purpose: The aim of this research was to study gender and social differences in adolescent sexuality and reproduction, as reflected in age at first intercourse and age at first pregnancy, as a basis for future interventions in the municipality of León, Nicaragua., Methods: In a community-based cross-sectional study including 7789 households, all women aged 15-49 years (n = 10,867) were interviewed about socioeconomic, sexual, and reproductive issues. A random subsample of men (n = 388) and women (n = 413) aged 15-49 years was interviewed in more detail about sexual patterns and reproduction., Results: The median age at first intercourse for women and men was 17.8 and 16.2 years, respectively. Women's average latency period to end of first pregnancy was 22 months. There was a significant tendency to start active sexual life later among today's girls aged 15-20 years, compared to the groups 21-27, 28-35, and 36-49 years old. A similar trend was found in age at first pregnancy. These secular trends were not found among men. Age at first pregnancy for current adolescents was lower among those having less formal education., Conclusions: The short latency period between first sexual intercourse and end of first pregnancy, probably reflecting lack of access to counseling and contraception, is worrying in light of the growing sexually transmitted disease/human immunodeficiency virus threat. The secular trend of later start of reproduction, however, is a positive sign which partly may be an effect of increasing education in the Nicaraguan society.

This investigation studied the effects of a shift from a well-balanced mixed diet to a lacto-vegetarian diet on the mutagenic activity in urine and feces and on some cancer-associated bacterial enzymes in human feces (beta-glucuronidase, beta-glucosidase, and sulphatase). Three months after the shift to the lacto-vegetarian diet, there was a significant decrease in mutagenic activity in urine and feces, beta-glucuronidase, beta-glucosidase, and sulphatase per gram feces wet weight. In contrast, the fecal mutagenic activity and the enzyme activities remained unchanged if expressed per daily output. However, the urinary mutagenic activity expressed as total daily output decreased. Part of the explanation for the decreased fecal mutagenic activity and the decreased enzyme activities is obviously a dilution effect, because much of the increased fecal weight after the shift in diet was associated with a higher water content.

The aim was to study the contraceptive patterns among men and women in León, Nicaragua. A questionnaire about sexual, contraceptive, reproductive and socioeconomic issues was directed to 7,789 households including 22% of all women of the municipality aged 15-49 years (n = 10,867). A subsample of 388 men and 413 women aged 15-49 years was drawn at random. Refusals were less than 2%. Private interviews revealed that among fertile women who had been sexually active within the last three months, non-pregnant and wishing to avoid pregnancy, 77% were contracepting. Female sterilization was the most common contraceptive method (39%), followed by intrauterine device (16%). Even though around 60% of women at some time had tried oral contraceptives, only 13% of contraceptors used them currently. The rhythm and interruption methods together constituted only 4%. Condom use was low and mainly occasional. Contraceptive use in sexually active women aged 15-44 years was lower among those having lower education, living in rural areas, and living under poverty conditions. The predominance of female sterilization and the occasional condom use-mainly reported by men-reflects a situation of relative male control over contraception and reproduction. This probably originates from "machista" values where men having many children with different women are considered strong. There was also a significantly higher use of contraceptives among the better-off women and men compared with the extremely poor. The situation of many poor women, in a country with limited contraceptive services, is worrying considering that abortion is illegal and the threat of HIV epidemic is growing. The situation for adolescents is particularly problematic with low experience in contraceptive use.

Total serum cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), apolipoprotein A-I (apo A-I), apolipoprotein B (apo B), and lipoprotein (a) (Lp(a)) were analysed in 879 14- and 17-year-old healthy adolescents (477 boys and 402 girls), and related to family history of cardiovascular disease, early feeding, weight and length at birth, and physical growth during infancy and childhood. Mean TC was significantly higher in girls than in boys (4.4 and 4.2 mmol/l, respectively, both age-groups together). High TC values ( > 5.2 mmol/l) were more prevalent in girls than in boys: 14% and 17% compared to 6% and 12% in 14- and 17-year-old girls and boys, respectively. Mean TC and LDL-C values were lower during mid-puberty in both boys and girls while, in boys but not in girls, mean HDL-C values decreased and TG values increased successively with increasing pubertal stage. Girls who were taking oral contraceptives had higher mean values of TC (4.91/4.39 mmol/l), TG (1.32/0.83 mmol/l), and apo B (0.89/0.73 g/l). Boys with a family history of early deaths ( < 55 years) from myocardial infarction and girls with a family history of cerebral haemorrhage/thrombosis in fathers had higher mean values of TC (4.55/4.17 and 5.03/4.40 mmol/l, for boys and girls, respectively), LDL-C (2.84/2.47 and 3.08/2.56 mmol/l), and apo B (0.73/0.70 and 0.86/0.73 g/l). Adolescents with short duration of breast feeding ( < 6 months), or early introduction of infant formula, had higher mean values of TC (4.29/4.14 mmol/l) and apo B (0.72/0.68 g/l). There were no significant correlations between serum lipid values and body weight or length at birth, but adolescents with high LDL-C (upper quartile) seemed to have lower attained heights during infancy and childhood. In conclusion, this study shows that serum lipids in adolescence are primarily related to age and sex but also to early determinants like family history of cardiovascular diseases, infant feeding, and early physical growth.

We present a method of partial purification of mitochondrial citrate transporter of the yeast Saccharomyces cerevisiae. Based on functional evidence of interaction between citrate transport and citrate synthase, we have used an affinity column containing pig heart citrate synthase (PHCS) for the purification. The purified preparation shows two protein components whose Mr is approximately 50K and 60K. The specific activity of our purest fractions is 2.6 mumoles/min which compares favorably to that of purified beef liver enzyme and purified rat liver enzyme.

The partition behavior of five glycolytic enzymes, in extracts from baker's yeast (Saccharomyces cerevisiae), between two aqueous phases has been studied by countercurrent distribution. All enzymes showed distribution patterns which indicated homogeneity and a similar partition behavior. In purified form, three of the enzymes (glyceraldehyde-phosphate dehydrogenase, 3-phosphoglycerate kinase, and enolase) showed the same partition behavior as in the extracts. Pure 6-phosphofructokinase, on the other hand, changed its partition distinctively relative to what was found in the extracts. These results indicate interactions between this enzyme and macromolecular compounds in the extracts and support a model suggested by Kurganov et al. (1985, J. Theor. Biol. 116, 509-526) describing a "glycolytic particle."

Herpes simplex virus (HSV) injection into the snout of mice was followed by the appearance of HSV antigen in neurons in trigeminal ganglia, main sensory and spinal tract trigeminal nuclei, reticular formation including raphe nuclei and locus ceruleus on both sides. The findings indicate that HSV spreads via axons, passes through a series of neurons and in this way can reach vital nuclei in the brainstem including monoaminergic neurons from the primary replication area in the lip.

We have directly compared in resting human mononuclear leukocytes the DNA repair effects caused by ADP-ribosyl transferase (ADPRT) activity following DNA damage induction by gamma radiation, UV radiation, ethylene oxide (EO) and N-acetoxy-2-acetylaminofluorene (NA-AAF). The presence of inhibitors of ADPRT during the quantitation of unscheduled DNA synthesis (UDS) resulted in about a 2-fold increase of UDS when induced by gamma radiation, UV radiation or EO. The stimulation of UDS by EO, UV- or gamma-radiation in the presence of an ADPRT inhibitor was equally strong whether 1 mM or 10 mM hydroxyurea was used to suppress scheduled DNA synthesis. The level of NA-AAF induced UDS was not affected by inhibitors of ADPRT. In addition, direct estimation of ADPRT activity revealed that at doses giving maximal UDS, NA-AAF damage did not induce a measurable enzymatic activity whereas gamma-radiation, UV radiation and EO all showed a significant dose response increase. We have interpreted our data to mean that NA-AAF induced UDS estimates DNA repair relating mainly to DNA lesions that are recognized with difficulty, and hence, the rate of endonuclease-induced DNA strand break accumulation is not sufficient to allow a stimulation of ADPRT and affect the quantitation of UDS.

Twelve herpes simplex virus (HSV) strains, 6 of each type, were inoculated subcutaneously into the left hind foot and into the cornea of the right eye of 12-day-old Swiss albino mice. The neural spread of virus to trigeminal and spinal ganglia and to brain and spinal cord was studied by demonstration of infective virus, histology and electron microscopy. Type 1 and type 2 infections seemed to spread equally well by intra-axonal transport. Using a protein tracer (horseradish peroxidase) injected into the same site as the virus, transport of the tracer to neurons corresponding to those infected with virus was observed. The extensive destruction of CNS tissue in the transitional region of the trigeminal root where CNS and the peripheral nervous system meet is discussed with reference to the pathogenesis of HSV encephalitis.

The extraction of cobalt, nicke cadmium and lead ions by means of APDC/MIBK has been studied at various acidities of the aqueous phase (pH 0.2-6). Lead and nickel are extracted equally well over this pH-range, while cobalt and cadmium require pH > 1. The time stability of the extracted complexes in MIBK increases in the order cadmium < lead < nickel < cobalt. The decomposition of the complexing agent or the metal complexes is rapid in the two-phase system MIBK/water.

The intracellular localization of ornithine decarboxylase (ODC), a key enzyme in polyamine synthesis and cell growth, is a matter of present debate. Using two independent methods of analysis, we have attempted to determine the actual distribution of ODC in a mammalian cell. To overcome the problem of a normally very low cellular ODC content, we have used ODC overproducing mutant CHO cells. These mutant cells exhibit a 10-fold higher ODC activity than do the wild type cells. The localization of ODC protein in exponentially growing cells, was determined by indirect immunofluorescence microscopy (permeabilized whole-cell preparations and 1 micron sections), using a monospecific ODC antibody. The intracellular localization of catalytically active ODC was determined by light and electron microscope autoradiography following pulselabeling of cells with alpha-difluoromethyl(5-3H)ornithine (3H-DFMO) at the time of peak ODC activity. alpha-Difluoromethylornithine (DFMO) is an enzyme-activated irreversible inhibitor of ODC and binds covalently to the active enzyme. The specificity of this reaction in the cell was ascertained by immunoprecipitation of 3H-DFMO-labeled ODC. ODC (as determined by both methods) was present in all the cells of a serum-stimulated monolayer culture. The highest concentration of ODC protein and of catalytically active ODC was observed in the smallest and most rapidly proliferating cells. Polyploid and multinuclear cells always exhibited the lowest concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Ethanol-intoxicated and non-intoxicated rats were injected with horseradish peroxidase and Evan's blue-labelled albumin and given a small air embolus in the right common carotid artery after ligation of the external carotid branch. In both ethanol-intoxicated and non-intoxicated rats, some endothelial cells, mainly in arteries and arterioles, showed a diffuse distribution of peroxidase in the cytoplasm. In some arterioles with a diffuse endothelial distribution of peroxidase there was a detachment of endothelial cells from the vessel wall, with an exposure of the adluminal basement membrane to blood elements. This endothelial detachment was mainly observed in ethanol-intoxicated rats. The vascular basement membranes underlying detached endothelial cells contained peroxidase, both in ethanol-intoxicated and in non-intoxicated rats. There was a considerable leakage of peroxidase via endothelial pinocytotic vesicles into the vascular basement membranes, mainly in arterioles, but also in capillaries and venules of the embolised hemisphere. This transendothelial pinocytotic transport of peroxidase was more prominent in ethanol-intoxicated than in non-intoxicated rats.

Mice were inoculated with herpes simplex virus (HSV) type 1 by gently scraping the skin of the nose with a fine needle. About 80% of the animals developed latent inapparent HSV infections in trigeminal ganglia. Virus was demonstrable for at least 6 months post inoculation (p.i.) by cocultivation of ganglionic tissue with GMK cells. Histologically, trigeminal ganglia revealed infiltrations of inflammatory cells even 6 months p.i. In addition, lesions occurred in the brainstem corresponding to the entry of trigeminal roots, trigeminal tracts and nuclei. Inflammatory cell infiltration, disruption of myelin sheaths and macrophages laden with myelin degradation products were observed 7 days p.i. Fourteen to 30 days p.i. electron microscopy demonstrated completely naked axons. In the transitional region of the trigeminal root denuded axons occurred in the central part of the region while the peripheral myelin, bordering the demyelinated central segments, was intact. Small areas of demyelination were still detectable 3 and 6 months p.i. but there were then also signs of remyelination. Possible mechanisms causing the demyelinations are discussed.

Ehrlich ascites tumor cells grown in the presence of inhibitors of ornithine decarboxylase (EC 4.1.1.17) exhibited an elevated content of this enzyme. The increase could not solely be explained by a decrease in the degradation rate of the enzyme. Instead a stimulation of enzyme synthesis, probably mediated via the polyamine-depleting properties of the inhibitors, is suggested. The enhancement of cellular ornithine decarboxylase content was not accompanied by any significant changes in the amount of ornithine decarboxylase mRNA, indicating a regulation at the level of translation.

Herpes simplex virus (HSV) infection of the mouse trigeminal ganglia and the brain stem is associated with demyelination of axons in the central part of the trigeminal root and inflammatory cell infiltration and perivascular demyelination in the brain stem. Cyclophosphamide (CPA) treatment prior to or soon after HSV inoculation caused increased axonal spread of infective virus from the peripheral site of inoculation, more widespread and severe demyelination and increased mortality, suggesting that by CPA the virus invasion of the CNS was facilitated. A direct cytocidal effect of HSV on myelinating cells seemed one plausible explanation for the demyelination. Influence on demyelination at late stages of infection by cytotoxic immune reactions are not excluded by the results reported but seemed not to dominate the picture. Schwann cells from the peripheral part of the nerve root invaded demyelinated areas in the brain stem and remyelinated the axons.

The levels of ADP-ribosyl transferase (ADPRT) activity following a standardized dose of 100 Gy gamma-radiation have been determined in leukocytes from 12 different mammalian species. Here, we report that the 100 Gy-induced levels of ADPRT correlated in a highly significant manner to the line spans of the mammals.

The distribution of the 14-3-2 protein in rat brain was investigated by immuno-electron microscopy using antiserum to the protein conjugated with peroxidase. 14-3-2 was demonstrated in the nuclear membrane, the endoplasmic reticular membranes and in the plasma membrane of nerve cells. The protein was also localized to the presynaptic densities and to the pre- and postsynaptic membranes. It could not be demonstrated in the membranes of the Golgi complex, inner membrane of mitochondria or in the nucleoplasm of neurons. No 14-3-2 protein was found in astrocytes, oligodendrocytes or in non-neuroectodermal tissue elements.

The expression of mammalian AdoMet decarboxylase, a key enzyme in polyamine synthesis, was shown to be regulated by polyamines at two different levels. Polyamine depletion of Ehrlich ascites tumor cells induced a marked compensatory increase in the synthesis of the enzyme, as measured by 35S-methionine pulse-labeling and immuno-precipitation. This increase in synthesis rate was counteracted by provision of spermidine, which reduced the synthesis of AdoMet decarboxylase to an undetectable level. Northern analysis revealed a nearly 2-fold increase in the amount of AdoMet decarboxylase mRNA when the putrescine and spermidine content was depleted. This increase in AdoMet decarboxylase mRNA content cannot account for the more than 5-fold increase in synthesis rate, indicating a feedback regulation also at the level of mRNA translation.

A particular phenol-formaldehyde resin of the resol type (P-F-R-2) was shown in a previous study to be a good tracer of patients with contact allergy to phenol-formaldehyde resins. Eleven patients with sensitivity to P-F-R-2 participated in the study in which chromatographically separated fractions of P-F-R-2 were patch tested. This procedure was repeated until a positive reaction to a single substance was noted. In this study 3 new sensitizers are reported. Investigations by mass spectrometry and nuclear magnetic resonance spectrometry identified the compounds to be 4,4'-dihydroxy-3-(hydroxymethyl)-diphenyl methane (4,4'-H-3-HPM), 4,4'-dihydroxy-3,3'-di-(hydroxymethyl)-diphenyl methane (4,4'-H-3,3'-HPM), and 4,4'-dihydroxy-3,5-di-(hydroxymethyl)-diphenyl methane (4,4'-H-3,5-HPM). Six of the 11 patients reacted to at least one of these compounds. All 6 patients reacted to 4,4'-H-3,3'-HPM and 5 reacted simultaneously to 4,4'-H-3-HPM. Four patients reacted to all 3 compounds tested. By patch testing with serial dilutions (ethanol 99.5%) of the three 4,4'-H-HPM, positive reactions were noted down to 0.5 X 10(-6)%, 1.0 X 10(-6)%, and 1.3 X 10(-3)% w/v for 4,4'-H-3-HPM, 4,4'-H-3,3'-HPM, and 4,4'-H-3,5-HPM, respectively.