Effects of transport age (14 d vs. 28 d of age) on blood total cholesterol, insulin and IGF-1 concentrations of veal calves.

The main aim of the current study was to find biomarkers of health in calves transported at different ages. The selected blood parameters were total cholesterol, insulin and IGF-1 and the longitudinal study investigated whether or not these concentrations were different between calves that were transported from the dairy farm to the veal farm at 14 d or 28 d of age. Relationships between these blood variables and health characteristics of veal calves were investigated. In a 34-wk study period, a total of 683 calves originating from 13 Dutch dairy farms were transported at an age of 14 or 28 d to 8 Dutch veal farms. Calves were blood sampled the first wk after birth (mean and SD: 4.4 ± 2.1 d), a day before transport (mean and SD: 25.8 ± 7.3 d) and in wk 2 post-transport (mean and SD: 36.7 ± 12.2 d). In these samples, insulin, IGF-1 and total cholesterol were determined and analyzed with a linear mixed model (LMM). Individual medical treatments were recorded from birth until the day of transport at the dairy farm, and from the moment of arrival at the veal farm until slaughter, and analyzed as a binary response variable (calf treated or not) with a generalized linear mixed model. Fecal (calf with or without loose or liquid manure) and navel (calves with or without swollen and inflamed navel) scores measured during a single visit in wk 2 post-transport were also analyzed as binary response variables, whereas carcass weights at slaughter age were analyzed with a LMM. Cholesterol, insulin and IGF-1 were included as covariates in the previous models to test their relationships with the likelihood of calves being medically treated, fecal and navel scores, and carcass weights. One day before transport 28 d-old calves had higher blood cholesterol (Δ = 0.40 mmol/l) and IGF-1 (Δ = 53.6 ng/ml) concentrations, and evidence of higher insulin (Δ = 12.2 µU/ml) compared with 14 d-old calves. In wk 2 post-transport, 28-d old calves had higher blood IGF-1 (Δ = 21.1 ng/ml), with evidence of higher insulin (Δ = 12.2 µU/ml) concentrations compared with 14-d old calves. Cholesterol concentration measured one day before transport and in wk 2 post-transport had a positive relationship with carcass weight at slaughter (ß = 4.8 and 7.7 kg/mmol/l, respectively). Blood cholesterol concentration in wk 2 post-transport was negatively associated with the fecal score measured at the same sampling moment (ß = -0.55/mmol/l), with the likelihood of a calf of being treated with antibiotics (ß = -0.36/mmol/l) and other medicines (ß = -0.45/mmol/l) at the veal farm. Blood IGF-1 concentration in wk 2 post-transport was negatively associated with the likelihood of a calf of being treated with antibiotics and other medicines (both ß = -0.01/ng/ml) at the veal farm, and with fecal score recorded in wk 2 post-transport (ß = -0.004/ng/ml). When looking at the blood indicators, it appeared that calves transported at 28 d of age were more developed compared with 14 d old calves, thus transport at an older age might be more beneficial for the animals. It can be concluded that both blood cholesterol and IGF-1 concentrations seemed to be valuable biomarkers of health and energy availability in veal calves.

Effect of light intensity on behaviour, health and growth of growing-finishing pigs.

The effect of light intensity has been explored in relation to endocrine functions and reproduction in pigs, but effects on health and behaviour are scarcely documented. The objective of this study was to evaluate the effects of different light intensities on behaviour, health and growth of growing-finishing pigs. An experiment was conducted on a commercial farm equipped with light-emitting diode-based luminaires creating four light intensity treatments: low (45 lux), medium (198 lux), high (968 lux) and spatial gradient of intensity (from 71 lux to 330 lux). Per treatment, 112 pigs were studied in two batches of eight pens. Once every two weeks behaviours such as exploration, positive and negative social interactions, play and abnormal behaviours were observed. Health issues were assessed weekly and included biting lesions, skin lesions, leg and respiratory disorders. The average daily gain over the experiment was calculated and after slaughter carcasses were inspected. Generalised linear mixed models were used for the analysis of behaviours, binary health scores, carcass abnormalities, ordinal logistic regression for multilevel health scores, and linear mixed models for average daily gain. Interactions between intensity and week were found for some behaviours (i.e., exploration, negative social interactions and abnormal behaviour) and health issues (i.e., tear stains, conjunctivitis, body lesions, bursitis and tail lesions). However, none of the treatments consistently outperformed another one. Light treatments did not affect pig growth and carcass abnormalities. These variable results support studies suggesting that pigs are adaptable to light intensities, and inconsistencies over weeks might have been caused by environmental factors that could not be controlled in a commercial farm setting. To conclude, tested light intensities had no clear effects on pig behaviour, health and growth.

Behavioral patterns as indicators of resilience after parturition in dairy cows.

During the transition phase, dairy cows are susceptible to develop postpartum diseases. Cows that stay healthy or recover rapidly can be considered to be more resilient in comparison to those that develop postpartum diseases. An indication of loss of resilience will allow for early intervention with preventive and supportive measures before the onset of disease. We investigated which quantitative behavioral characteristics during the dry period could be used as indicators of reduced resilience after calving, using noninvasive Smart Tag neck and Smart Tag leg sensors in dairy cows (Nedap N.V.). We followed 180 cows during 2 wk before until 6 wk after parturition at 4 farms in the Netherlands. Serving as proxy for loss of resilience, as defined by the duration and severity of disease, a clinical assessment was performed twice weekly and blood samples were taken in the first and fifth week after parturition. For each cow, clinical and serum value deviations were aggregated into a total deficit score (TDS total). We also calculated TDS values relating to inflammation, locomotion, or metabolic problems, which were further divided into macro-mineral and liver-related deviations. Smart Tag neck and leg sensors provided continuous behavioral activity signals of which we calculated the average, variance, and autocorrelation during the dry period. Diurnal patterns in the behavioral activity signals were derived by fast Fourier transformation and the calculation of the nonperiodicity. To select significant predictors of resilience, we first performed a univariate analysis with TDS as dependent variable and the behavioral characteristics that were measured during the dry period, as potential predictors with cow as experimental unit. We included parity group as fixed effect and farm as random effect. Next, we performed multivariable analysis with only significant predictors, followed by a variable selection procedure to obtain a final linear mixed model with an optimal subset of predictors with parity group as fixed effect and farm as random effect. The TDS total was best predicted by average inactive time, nonperiodicity ruminating, nonperiodicity of bouts standing up and fast Fourier transformation stand still. Average inactive time was negatively correlated with average eating time, and these 2 predictors could be exchanged with only little difference in model performance. Our best performing model predicted TDS total at a cutoff level of 60 points, with a sensitivity of 79.5% and a specificity of 73.2% with a positive predicted value of 0.69 and a negative predicted value of 0.83. The models to predict the other TDS categories showed a lower predictive performance as compared with the TDS total model, which could be related to the limited sample size and therefore, low occurrence of problems within a specific TDS category. Furthermore, more resilient dairy cows are characterized by high averages of eating time with high regularity in rumination and low averages of inactive time. They reveal high regularity in standing time and transitions from lying to standing, in the dry period. These behaviors can be used as indicators of resilience and allow for preventive intervention during the dry period in vulnerable dairy cattle. However, further examination is still required to find clues for adequate intervention strategies.

Calf and dam characteristics and calf transport age affect immunoglobulin titers and hematological parameters of veal calves.

This study aimed to investigate effects of transport age of calves (14 vs. 28 d), and of calf and dam characteristics, on immunoglobulin titers and hematological variables of veal calves. Calves (n = 683) were transported to a veal farm at 14 or 28 d of age. Natural antibodies N-IgG, N-IgM, and N-IgA against phosphorylcholine conjugated to bovine serum albumin (PC-BSA) were measured in serum of the dams 1 wk before calving and in first colostrum. These antibodies were also measured in serum of calves 1 wk after birth, 1 d before transport, and in wk 2 and 10 posttransport at the veal farm. Hematological variables were assessed in calves 1 d before transport and in wk 2 posttransport. One day before transport, titers of N-IgG, N-IgM, N-IgA, and neutrophil counts were higher, and lymphocyte counts were lower in 14-d-old calves compared with 28-d-old calves. In wk 2 at the veal farm, calves transported at 14 d of age had higher N-IgG titers and neutrophil counts, but lower N-IgM and N-IgA titers, and lymphocyte counts than calves transported at 28 d. In wk 1 and 1 d before transport, N-Ig in calves were positively related to N-Ig in colostrum. In wk 2 and 10 at the veal farm, N-IgG in calves was positively related to N-IgG in colostrum. The N-IgG titers in calves at the dairy farm were negatively related to the likelihood of being individually treated with antibiotics or other medicines at the veal farm. Our results suggest that calves transported to the veal farm at 28 d of age showed a more advanced development of their adaptive immunity than calves transported at 14 d of age. Quality of colostrum might have long-term consequences for N-IgG titers and immunity in veal calves.

Effects of transport age and calf and maternal characteristics on health and performance of veal calves.

The objective of this study was to investigate effects of calf transport age (14 vs. 28 d) and calf (e.g., sex and breed) and dam characteristics (e.g., parity and ease of birth) on health and performance of veal calves until slaughter age. Calves (n = 683) originated from 13 dairy farms in the Netherlands and were transported at either 14 or 28 d of age from the dairy farm to 8 Dutch veal farms. A health assessment of calves was performed on a weekly basis at the dairy farm and in wk 2, 10, 18, and 24 at the veal farm. Body weight of calves was measured on a weekly basis at the dairy farm and upon arrival at the veal farm. At the veal farm, use of antibiotics and other medicines during the rearing period (both at herd and individual level) was recorded and carcass weights were obtained from the slaughterhouse. Body weight upon arrival (Δ = 11.8 kg) and carcass weight at slaughter (Δ = 14.8 kg) were greater, and mortality risk (Δ = -3.1%) and prevalence of animals treated with medicines other than antibiotics (e.g., antiinflammatories, multivitamins, and anticoccidial drugs; Δ = -5.4%) were lower in calves transported at 28 d compared with calves transported at 14 d. Crossbreds other than Belgian Blue × Holstein Friesian received a higher number of individual treatments with antibiotics and other medicines (Δ = 14.8% and Δ = 15.1%, respectively) at the veal farm compared with Belgian Blue × Holstein Friesian calves. These findings suggest that calves transported at 28 d were more robust compared with calves transported at 14 d.

Comparison of two methodologies used to estimate erosion rates in Mediterranean ecosystems: 137Cs and exposed tree roots.

The 137Cs deposited in soil and exposed tree roots have been widely applied to estimate medium-term soil erosion rates. However, comparative studies between these methods are scarce. For this purpose, three hillsides in two Mediterranean dehesas (rangeland with disperse tree cover) were selected. Regarding the 137Cs technique, a reference site close to the study areas and with similar altitude and rainfall was selected. In order to reduce uncertainties related to the use of point soil profiles, all those collected in an area were combined to form a representative composite profile. The total inventory was 2790±50Bq/m2, and the relaxation coefficient indicated it was an undisturbed soil. The radiocaesium inventory in the study areas was 14-23% lower than in the reference area. The erosion rates for 137Cs were in the range 20.9-38.1tha-1y-1. The exposed root technique was applied to holm oak trees (age about 90years), and the erosion rates were in the range 22-34tha-1y-1. The ratio between exposed root and 137Cs techniques was 1.02±0.11 (S.D.) within the range 0.89-1.2. Both methods produced very similar results equally with respect to the mean erosion rate as well as the relative difference between the hillslope sections, i.e. displaying the same spatial variation in the study areas. As the accounting time for these two techniques is different, 50 and 90y for 137Cs and exposed roots respectively, results suggest that no change in mid-term erosion rates was implied for these areas for almost a century. The use of 137Cs and exposed roots methodology for the determination of mean erosion rates can be reproduced in other ecosystems, but a careful selection of the reference site for 137Cs is essential.

Evaluating the influence of physical, economic and managerial factors on sheet erosion in rangelands of SW Spain by performing a sensitivity analysis on an integrated dynamic model.

An integrated dynamic model was used to evaluate the influence of climatic, soil, pastoral, economic and managerial factors on sheet erosion in rangelands of SW Spain (dehesas). This was achieved by means of a variance-based sensitivity analysis. Topsoil erodibility, climate change and a combined factor related to soil water storage capacity and the pasture production function were the factors which influenced water erosion the most. Of them, climate change is the main source of uncertainty, though in this study it caused a reduction in the mean and the variance of long-term erosion rates. The economic and managerial factors showed scant influence on soil erosion, meaning that it is unlikely to find such influence in the study area for the time being. This is because the low profitability of the livestock business maintains stocking rates at low levels. However, the potential impact of livestock, through which economic and managerial factors affect soil erosion, proved to be greater in absolute value than the impact of climate change. Therefore, if changes in some economic or managerial factors led to higher stocking rates in the future, significant increases in erosion rates would be expected.

Prediction of near-surface soil moisture at large scale by digital terrain modeling and neural networks.

The capability of Artificial Neural Network models to forecast near-surface soil moisture at fine spatial scale resolution has been tested for a 99.5 ha watershed located in SW Spain using several easy to achieve digital models of topographic and land cover variables as inputs and a series of soil moisture measurements as training data set. The study methods were designed in order to determining the potentials of the neural network model as a tool to gain insight into soil moisture distribution factors and also in order to optimize the data sampling scheme finding the optimum size of the training data set. Results suggest the efficiency of the methods in forecasting soil moisture, as a tool to assess the optimum number of field samples, and the importance of the variables selected in explaining the final map obtained.

[Frequency and causes of civil and criminal proceedings in radiology. Analysis of a survey]. / Häufigkeit und Ursache zivil- und strafrechtlicher Verfahren in der Radiologie. Auswertung einer Befragung.

The eagerness of German patients to go to court on account of actual or suspected malpractice of their physicians has increased over the years, as is the case in other Western countries. Media coverage has given rise to criticism of physicians and their services rendered more than before. This naturally also concerns the discipline of radiology, even though the probability of a radiologist being accused in a lawsuit is clearly minor in comparison to the surgical disciplines. In contrast to other fields, the X-ray pictures are always available for a second opinion. In this study, 4760 radiologists were sent a questionnaire by mail and 1503 answered. The questionnaires were evaluated regarding interrogative and informative data from pending or completed proceedings. Lawsuits were directed towards the assessment of examinations (38%), the actual performance of an examination (30%) and not towards providing patients with information as we had expected. Angiographies, mammographies, and radiographies were the most frequent reasons for instituting proceedings. The majority of litigating patients was between 40 and 50 years old. The proceedings led to civil convictions in 30% and criminal convictions in 5.5%. Of the physicians accused of incorrect conduct, 73% were of the opinion that they had been treated unjustly, 26% supported the reproach as justified, and the rest had formed no opinion. Physicians in private practice and senior consultants (70%) were most frequently sued.

[Effectiveness of echinacin in therapy of chronic recurrent respiratory disease]. / Nutzenbewertung der Therapie chronisch rezidivierender Atemwegsinfekte mit Echinacin.

PURPOSE: Echinacea purpurea (echinacin) is frequently used in the therapy of chronic recurrent respiratory disease. The aim of this study was to show whether treatment of chronic recurrent respiratory disease with echinacin has a greater benefit in terms of effectiveness than therapy without an immunomodulator. MATERIALS AND METHODS: Frequency, duration of recurrence, resources used and patients' satisfaction was documented in order to assess benefit. In this prospective, non-randomised, multi-centre, nationwide, two-armed health services research study, data of 995 patients (782 echinacin-, 213 standard-cohort) with chronic recurrent respiratory disease were collected. The perspectives of statutory health insurance (SHI), patients and health policy were taken into consideration. RESULTS: The risk of falling ill was 2.3 fold higher and the duration of relapse 1.4 days more compared to the standard-cohort. There was a clinical and economical benefit from the therapy with echinacin for SHI and health policies. In contrast, patients experienced a greater financial burden. Average total costs per patient during the observation period of 3 months amounted to 238.35 in the standard-cohort and to 228.95 in the echinacin-cohort. Results of the intent-to-treat-analysis were reconfirmed in a per-protocol-analysis. CONCLUSION: This health services-research-study taking the therapy of chronic recurrent respiratory disease with echinacin as an example has shown that even non-prescription drugs can have clinical and economic benefits.

Nisoldipine increases the bioavailability of endothelial NO.

Different observations suggest that dihydropyridine calcium antagonists alter endothelial NO release. Therefore, in a first step we investigated whether part of the nisoldipine (a dihydropyridine calcium antagonist with a possible selectivity for coronaries)-induced vasorelaxation was due to an NO release from the endothelium in porcine coronary arteries. Secondly, we directly measured whether nisoldipine increased NO release from rabbit aorta or the nisoldipine enantiomers (Bay R 1223, Bay R 1224) from rat aorta. Thirdly, we determined whether nisoldipine exerted antioxidative properties in segments of porcine aorta with intact endothelium. Blocking endothelial NO synthase with N-nitro-L-arginine resulted in a significant shift of the relaxation curve to higher concentrations. Accordingly, nisoldipine induced a concentration-dependent release of NO (direct electrochemical detection) from native endothelium which already started at a therapeutical level (1 nmol/l nisoldipine/6.5 +/- 1.2 nmol/l NO). To evaluate whether this effect was due to an antioxidative protection of NO, we examined the influence of nisoldipine on a hyperglycemia (30 mmol/l, 20 min)-induced reactive oxygen species release of vascular endothelium from porcine coronary arteries. Nisoldipine concentration-dependently reduced the reactive oxygen species release (>50%; 10 micromol/l). Moreover, a carbachol-induced NO release (rabbit aorta) which was significantly diminished by hyperglycemia was completely restored in the presence of nisoldipine (3 micromol/l). We conclude that nisoldipine increases the NO bioavailability which may result in an ameliorated endothelial function.

A new method to measure nitrate/nitrite with a NO-sensitive electrode.

There are different methods to measure the unstable molecule nitric oxide (NO). We will describe a new sensitive method to measure NO by reconversion of nitrate/nitrite to NO, which will be determined with an amperometric Clark-type electrode. Nitrate and nitrite are the degradation products of NO. First, nitrate is enzymatically converted to nitrite with the use of the nitrate reductase. Second, nitrite is reduced to equimolar NO concentrations by an acidic iodide solution. The detection limit of the electrode in an aqueous solution was 2 nmol/l NO (meaning the threshold was depending on the volume added: 500 microl of a 0.2 micromol/l nitrite solution added to a 10-ml bath). This method provides the ability to assess basal and agonist-stimulated NO releases of different biological models. We measured basal and carbachol-stimulated NO release of native endothelial cells from porcine coronary arteries and porcine aortic endothelial cell cultures. Moreover, it was possible to measure the nitrate/nitrite concentration in the coronary effluent of a guinea pig heart. In conclusion, we present a valid, highly sensitive new method of measuring nitrite/NO in biological systems with a commercially available electrode.

Early orthodontic treatment of Class-III malocclusion in Germany.

In order to evaluate current attitudes to early interceptive treatment, 2001 orthodontic offices in Germany were asked to fill in a questionnaire comprising the following topics: indication, appliances for the early correction of Class-III malocclusions, diagnostic records, duration, and benefits to overall therapy. Based on the 677 evaluable questionnaires, the following statistically significant conclusions could be drawn: 92.6% of the orthodontists see Class-III malocclusion as an indication for early treatment. Early treatment of severe crowding, diastemata, Class-II malocclusion, deep bite, increased overjet and impacted incisors was declined by most orthodontists. The interceptive treatment of further malocclusions was controversially discussed. Functional appliances (67.5%), in particular the Fränkel III (47.3%), were dominant in correction of Class-III malocclusions. Typical orthodontic records relating to early interceptive treatment include panoramic radiographs, lateral headfilms, photos and dental casts. 2.5% of the orthodontists routinely take a hand-wrist radiograph. Although recently published studies support the use of facial masks in theory, they are rarely used in practice. To what extent early interceptive treatment of Class-III malocclusion influences the overall treatment is the subject of further studies.

c-erbB-2 in serum of patients receiving fractionated paclitaxel chemotherapy.

Humanized anti-c-erbB-2 antibodies (Herceptin) in a weekly schedule are a new therapeutic option for the treatment of c-erbB-2-positive, advanced breast cancer (ABC). Addition of Herceptin to first-line chemotherapy for c-erbB-2 overexpressing ABC increased anticancer activity in a randomized phase III trial. However, except from standard UICC response criteria, there are hitherto no recommendations as to how to monitor Herceptin therapy. In a therapy optimizing study with weekly dose-intensified paclitaxel monotherapy (schedule: 90 mg/m2 weekly x 6, q9w), we correlated the clinical course of stage IV breast cancer in UICC criteria with the course of the shed c-erbB-2 protein fragment and the CA 27.29 serum level. Serum samples were taken weekly from 35 patients to measure the serum c-erbB-2 and CA 27.29 protein levels over time. Up to now, 10 patients (28.5%) are c-erbB-2 positive (> 15 U/mL), with a median baseline protein expression of 65 U/mL. While the overall response rate in the study is 36%, the response rate among c-erbB-2-positive patients is 62%, indicating a high sensitivity of c-erbB-2 positive patients to dose-intense paclitaxel treatment. In all responders the c-erbB-2 serum level decreased below the detection limit either before the clinical diagnosis of response or by the end of the next cycle. However, the normalization of the c-erbB-2 serum level was not specific for responders as patients with stable or progressive disease presented normalized levels or a > 50% decrease of the baseline level, too. The courses of the c-erbB-2 protein levels correlated closely with the courses of CA 27.29. The decrease in the serum c-erbB-2 oncoprotein level might indicate a regression of c-erbB-2 positive tumor load. This may even happen in progressive disease according to UICC criteria when the c-erbB-2-negative tumor fraction progresses while the c-erbB-2-positive fraction is controlled. Another explanation would be that the mechanisms of c-erbB-2 shedding change under chemotherapy, with less of the c-erbB-2 protein fragment being released to the serum, which would make the c-erbB-2 positive tumor cells a better target for anti-c-erbB-2 antibody treatment.

Procalcitonin--influence of temperature, storage, anticoagulation and arterial or venous asservation of blood samples on procalcitonin concentrations.

In this study we have analysed the influence of temperature and time of storage and of repeated freezing on procalcitonin plasma concentrations ex vivo. We have also analysed the difference of procalcitonin concentrations in arterial or venous blood samples and the influence of different anticoagulation techniques on procalcitonin concentrations (serum, EDTA-, lithium-heparin- or citrate plasma). At room temperature (25 degrees C) a loss of procalcitonin plasma concentrations of 6.4% +/- 2.6% (mean, 2 standard error of the mean) after 3 hours (4.6% +/- 5.2% at 4 degrees C) and 12.3% +/- 3.1% after 24 hours occurred (6.3% +/- 5.0% at 4 degrees C, n = 17 each). Comparing the procalcitonin concentrations of blood samples with different anticoagulants (n = 24 each), there was only a significant difference between procalcitonin concentrations in heparinized plasma and serum (+ 7.6%, difference of the mean). There was no significant influence of the blood sampling technique (arterial or venous line) and of repeated freezing/thawing cycles (up to 3 times) on the procalcitonin concentrations measured. Although the difference of sampling and storage of the blood on procalcitonin concentrations is not significant, multiple factors may act synergistically on the result of procalcitonin measurement. To keep variations of ex vivo conditions as minimal as possible, a standardized technique of anticoagulation, time and temperature of storage is recommended, e.g. the use of EDTA-plasma and storage at room temperature, when samples are measured within 4 hours after blood drawing.

Normal liver chromatin contains a firmly bound and larger protein related to the principal cytosolic target polypeptide of a hepatic carcinogen.

A 14,000-dalton polypeptide was previously reported to be the principal protein target of the carcinogen N-2-fluorenylacetamide (2-acetylaminofluorene) in liver cytosol at the start of hepatocarcinogenesis in rats. The 14,000-dalton polypeptide was purified to homogeneity according to gel electrophoreses in both NaDodSO4-containing medium and acetic acid/urea and also by immunogenicity. An immunologically related form of the cytosolic target polypeptide has now been found to be present in the nuclei of normal rat liver as a 17,500-dalton polypeptide that is firmly and ionically bound to chromatin. Serial salt extractions of isolated liver nuclei or chromatin at 0.15 and 0.35 ionic strengths fail to dissolve the bound polypeptide, according to electrophoretic transfer immunoblot analyses. Most of the 17,500-dalton polypeptide is extracted at 0.65 ionic strength, the remainder at 1.2, and none at 2.0, nor thereafter in 8 M urea. In addition, short-term digestion of purified liver nuclei with micrococcal nuclease solubilizes the 17,500-dalton polypeptide. All three protocols also solubilize low levels of intermediate 17,500- to 14,000-dalton species, the latter size being the same as that of the cytosolic protein target of the carcinogen. The presence of protease inhibitors during the isolations and extractions of the nuclei and chromatin reduces the amounts of these smaller polypeptides. In normal rat liver only nuclei and cytoplasm of hepatocytes contain reactive antigen according to peroxidase-antiperoxidase immunohistochemistry, staining most intensely perilobularly, less in the lobular midzone, and least centrilobularly. The nuclei of the perilobular hepatocytes constitute the strongest staining compartment within all of normal liver. Of 22 nonhepatic tissues of normal rats, 16 contain relatively few cells with immunoreactive cytoplasm. Nonhepatic nuclear antigen is present only in villar crest cells of duodenum (which are normally exposed to liver bile), also having cytoplasmic antigen as well. Five kinds of evidence appear to connect the chromatin-bound 17,500-dalton polypeptide of normal liver nuclei to the cytosolic 14,000-dalton polypeptide that is the principal target of the carcinogen early during hepatocarcinogenesis in rats. The present findings indicate a direct connection between a chromosomal protein and the immediate principal cytosolic protein target of a carcinogen.

Action of local anesthetics on intensity of lipid transition of phospholipids in human red cell membrane.

Anilinonaphthalene-8-sulfonate (ANS) response over a temperature range was measured in red cell membrane under the influence of a series of local anesthetics. Ratios of slopes before (m1) and after (m2) lipid transition temperature were calculated. The sequence of m1/m2 shows a correlation with Ki values of glucose transport in erythrocytes. For some substances, the rates of esterification of cholesterol in microsomal membrane and the clinical effectiveness increase in the same sequence. The present investigations further underline the concept that the penetrating power of the local anesthetics runs parallel with their biological activity.