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Effect of acetylation on monoclonal antibody ZCE-025 Fab': distribution in normal and tumor-bearing mice.

Studies were performed to determine in vitro and in vivo effects of acetylation on Fab' fragments of ZCE-025, a monoclonal anti-CEA antibody. Isoelectric focusing revealed a drop in isoelectric point of 1.7 pI units following acetylation. Biodistribution studies of acetylated and nonacetylated [111In]Fab' were performed in normal BALB/c mice and in nude mice bearing the T-380 CEA-producing human colon tumor. The acetylated fragments remained in the vascular compartment longer and had significantly diminished renal uptake of 111In compared to controls. While acetylation itself effected a 50% drop in immunoreactivity, tumor uptake of the acetylated and nonacetylated 111In-labeled Fab' fragments was comparable, with the exception of one data point, through 72 h.

Acetylation↗

Sodium channel distribution in normal and denervated rodent and snake skeletal muscle.

1. Sodium channel current density was measured using the loose-patch voltage clamp technique. Innervated rat, mouse and snake muscle had the highest density of Na+ channels in the end-plate region. These high Na+ channel densities were maintained in denervated muscle. 2. Perijunctional membrane had a Na+ current density 5- to 10-fold greater than the density several hundred micrometres from the end-plate. In all muscles this concentration of channels near the end-plate persisted following denervation. 3. At the tendon Na+ current density fell to low values (approximately 1 mA/cm2). The decrease in density began about 300-500 microns from the tendon. This pattern was found in all snake twitch fibres and fast-twitch (EDL) rat and mouse muscle fibres. This reduction in channel density near the tendon was not affected by denervation. 4. Sodium channels in all regions of innervated rat and snake muscle fibres were highly sensitive to tetrodotoxin (TTX). Sodium channels in snake muscle remained sensitive to TTX after denervation. Sodium channels that are relatively resistant to TTX appeared in rat muscle after denervation. TTX-resistant channels were even more concentrated near the end-plate than were TTX-sensitive channels in innervated muscle. At the tendon TTX-resistant Na+ channel density decreased. 5. We conclude that although the nerve presumably directs the localization of Na+ channels during development, the ability to maintain this distribution and to control the distribution of newly appearing channels persists long after the nerve has been removed.

Action Potentials↗

Normative data for passive ankle plantarflexion--dorsiflexion flexibility.

OBJECTIVE: To describe the normal distribution parameters for measures of passive ankle plantarflexion-dorsiflexion flexibility obtained from a large sample of able-bodied young adult subjects. DESIGN: Seven variables were assessed and descriptive analyses were conducted. BACKGROUND: While assessment of plantarflexion-dorsiflexion flexibility is an important component of a clinical examination of plantarflexion contracture, there is limited normative data available that can be used as a reference for clinical decision-making. METHODS: Data were collected from 300 able-bodied male and female subjects aged between 15 and 34 years. Both ankles were measured. Load-displacement curves were collected using a manually controlled instrumented footplate. Six variables were extracted from these curves: passive torque at zero and 10 deg, passive stiffness at zero and 10 deg, and two coefficients from an equation fitted to the curve (i.e., k and b). The seventh variable, passive dorsiflexion range of motion, was quantified using a clinical procedure. RESULTS: Flexibility variables did not differ between the left and right ankles, nor between the dominant and non-dominant legs. All variables were normally distributed. These distributions can, therefore, be adequately described using their mean and standard deviation values. CONCLUSIONS: This study has substantially increased the available database on plantarflexion-dorsiflexion flexibility and forms the basis of norm-referenced clinical tests.

Adolescent↗

How many blows really make an FEV1, FVC, or PEFR?

We have collected peak expiratory flow rates, one-second forced expiratory volumes, and forced vital capacities in sets of 10 or 20 values at one-minute intervals from 30 normal, 49 asthmatic, and 26 bronchitic subjects. Analysis shows that the derivatives are compatible with a normal distribution of the values in the sets, so that the true value is best represented by the arithmetic mean of all valid attempts. One-third of all subjects showed skewness in one or more indices but these were equally divided between positive and negative directions. There is no sign of the dominant negative skewness that would result if the true value was indeed a maximum, which could be approached or equalled but never exceeded. There is no sign that repetition worsens performance. Seventy-two subjects showed no regression in any index and those of the remainder who deteriorated were balanced by equal numbers in all categories who improved. There is a significant tendency for both the highest and the lowest values to occur in the earlier part of any series. Probability theory suggests that this is a statistical phenomenon. The best estimate of the true value of these indices is probably the mean of as many observations as can be conveniently obtained and the data can be treated statistically as if they were a sample from a normally distributed population.

Adolescent↗

The effect of the area under the plasma concentration vs time curve and the maximum plasma concentration of esomeprazole on intragastric pH.

OBJECTIVE: The aim of this study was to create a useful model of the effect of the area under the plasma concentration vs time curve (AUC) and the maximum plasma concentration (C(max)) of esomeprazole on intragastric pH, measured as the percentage of total time with intragastric pH above 4 (%pH>4) during a 24-h period. METHODS: The evaluation is based on esomeprazole data from two crossover studies. In the first study ( n=36), intragastric pH and plasma concentrations were measured on day 5 of repeated once-daily 20-mg and 40-mg doses of esomeprazole during fasting conditions. In the second study ( n=24), measurements were made on days 1 and 5 of repeated once-daily dosing with 40 mg of esomeprazole under fasting and fed conditions. A model was applied in which the logistic function of %pH>4 was assumed to be linearly dependent on log-transformed AUC and C(max). The effects of repeated dosing and of fed relative to fasting conditions were included in the model, and the interindividual variation in %pH>4 was accounted for. RESULTS: The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error. In this model, log-transformed AUC and C(max) were both statistically significant. The model showed that for a fixed AUC, a decrease in C(max) gives an increase in %pH>4. A decrease in AUC, keeping C(max) fixed, gives a decrease in %pH>4, but a simultaneous decrease in C(max) and AUC will result in a less pronounced decrease in %pH>4. The model may be used for predicting differences in %pH>4 between two formulations, based on assessments of AUC and C(max). Repeated dosing gave an increased %pH>4, where approximately half of the increase stemmed from increased AUC and C(max), and the rest could be attributable to the persistent blockade of the proton pumps. Food intake reduced AUC and C(max) but had no obvious effect on %pH>4, which is explained by a prolonged time period with quantifiable plasma concentrations. CONCLUSION: The effect of the pharmacokinetic variables AUC and C(max) of esomeprazole on %pH>4 can be adequately described by a model using a logistic function for %pH>4 and a normally distributed error.

Administration, Oral↗

Angiographic manifestations and operative findings with 70 cases of hemifacial spasm: relation of common trunk anomalies.

The relations between angiographic manifestations and operative findings of hemifacial spasm were studied in 70 cases between 1988 and 2001. Vertebral angiography was performed, and Towne, straight AP, and lateral projections were routinely examined. The dominant anterior inferior cerebellar artery (AICA) directly compressed the facial nerve root exit zone in 26 cases, the dominant posterior inferior cerebellar artery (PICA) in 20, the AICA in 13, the PICA in 2, and the vertebral artery (VA) in 9. Compression by multiple vessels was observed in 11 cases. Anatomical variations of the affected AICA and PICA were classified into 3 groups according to their origins and distributions of blood supply: normal distribution of AICA and PICA in 18%, common trunk anomaly with dominant AICA (basilar artery origin) in 48% and common trunk anomaly with dominant PICA (vertebral artery origin) in 34%. Analyses of the angiograms revealed significantly increased numbers of common trunk anomalies compared with cases with normal angiograms. In 18 of the 20 cases of unilateral common trunk anomalies, facial nerves were compressed by the dominant artery. Preoperative vertebral angiograms may clarify the offending vessels and their sites in most hemifacial spasm cases, thus increasing the safety of surgical interventions.

Adult↗

[Preparation of monospecific antibodies to A-protein and an immunochemical study of its distribution in normal and tumorous tissues].

Monospecific antibodies against A-protein from rat liver cytosol were prepared. Complete nonidentity was established in comparison of the A-protein and ligandin, which was similar to A-protein in binding properties. Besides, A-protein found in cytosol of liver tissue was present in cytosol of small intestine. It was not found in the cytosol of other 17 tissues. A-protein appeared in ontogenesis earlier than ligandin: its concentration sharply increased in rat embryonal liver within 16--18 day of gestation. Level of A-protein was decreased 2--4-fold in primary rat hepatomas. A-protein and ligandin are the isoforms of binding proteins, which characterize different steps of the differentiation of the hepatocytes.

Animals↗

Variability of renal echo-Doppler measurements in healthy adults.

BACKGROUND: We examined the most widely used echo-Doppler variables in healthy adults to define their normal distribution and variability in relation to age, sex, body surface area and the right and left kidney. METHODS: Ninety healthy subjects were selected, stratified for sex and age (range 20-65 years). We also examined 8 subjects with a congenital solitary kidney and 15 surgically nephrectomized patients. Variables studied were the diameters and volume of the kidneys, renal blood flow (RBF) and resistive index (RI) measured on the renal, interlobar and cortical arteries. RESULTS: The mean length was greater in the left kidney (p<0.01) and width in the right one (p<0.02). Volume was no different on the two sides. RBF showed an age-dependent reduction (p<0.0001), while interlobar (p<0.0001) and cortical (p<0.0001) RI showed a selective age-dependent increase. RI were higher in females and diameters, volume and RBF, after correction for body surface area, were not different in the two sexes. Cortical RI was lower than the interlobar and renal RI (p<0.0001). In the group with congenital single kidney, length, volume and RBF were all greater. In the mononephrectomized patients, length and volume were greater but RBF was the same as in a normal single kidney. CONCLUSIONS: The ultrasonographic and Doppler variables studied did not show any differences from normal distribution but they were influenced differently by some demographic parameters; however, the integrated use of these measurements offers precision and repeatibility, and could help evaluating diffuse or localized abnormalities.

Adult↗

Haemoglobin and ferritin concentrations in children aged 12 and 18 months. ALSPAC Children in Focus Study Team.

AIMS: To define the normal ranges and investigate associated factors for haemoglobin and ferritin in British children at 12 and 18 months of age, and to estimate correlations between both haemoglobin and ferritin concentrations at 8, 12, and 18 months of age. SUBJECTS AND METHODS: Subjects were part of the "children in focus" sample, randomly selected from the Avon longitudinal study of pregnancy and childhood. Capillary blood samples were taken from 940 children at 12 months and 827 children at 18 months of age. RESULTS: Haemoglobin was distributed normally and ferritin was distributed log normally at 12 and 18 months of age. Ninety five per cent reference ranges were established from empirical centiles of haemoglobin and ferritin. Haemoglobin concentrations at 18 months were associated with sex and maternal education. Concentrations of ferritin at 12 and 18 months of age were associated with birth weight and current weight. Girls at 12 months, but not at 18 months, had 8% higher ferritin concentrations than boys. Haemoglobin and ferritin concentrations were significantly correlated over time (8-12 months: rHb = 0.26, rFer = 0.46; 12-18 months: rHb = 0.37, rFer = 0.34; 8-18 months: rHb = 0.22, rFer = 0.24). CONCLUSION: Iron stores are depleted by rapid growth in infancy. A definition of anaemia based on the fifth centile gives cut off points at 12 and 18 months of age of haemoglobin < 100 g/l, and for iron deficiency of ferritin < 16 micrograms/l and < 12 micrograms/l, respectively. Because children below the fifth centile at one time point differ from those six months later, it is unclear whether screening would be effective.

Age Factors↗

Susceptibility to diabetes is widely distributed in normal class IIu haplotype rats.

AIMS/HYPOTHESIS: We did experiments to explore the pathways putatively leading to Type I (insulin-dependent) diabetes mellitus, and their association with the MHC locus, the major genetic determinant of disease susceptibility. METHODS: Normal MHC congenic rat strains that do not spontaneously develop diabetes or any other autoimmune syndrome were injected with the interferon-alpha inducer polyinosinic-polycytidylic acid (Poly IC). RESULTS: Insulitis and diabetes developed only in strains expressing Class II(u) genes and was independent of the Class I haplotype. Poly IC induced islet cell Class I hyperexpression, up regulation of pancreatic endothelial intercellular adhesion molecule-1 and vascular adhesion molecule-1 and a T-cell and macrophage infiltration of the pancreatic interstitium in all rat strains studied, including diabetes-resistant strains. Poly IC also induced the generation of diabetes-transferring spleen cells in most Class II(u) haplotype rats, including the diabetes-resistant WF rat. CONCLUSION/INTERPRETATION: The minimum requirements for autoimmune diabetes development in the rat include: RT1 Class II(u) genes, a T-cell repertoire containing beta-cell autoreactive T cells and a triggering event which breaks tolerance by the local up regulation of pancreatic endothelial adhesion receptors. Even when all of the minimum requirements have, however, been met, most Class II(u) rats do not develop diabetes in response to autoimmune stimuli. It is clear, nonetheless, that susceptibility to diabetes is widely distributed in the RT1(u) rat.

Adoptive Transfer↗

Measuring changes in logarithmic data, with special reference to bronchial responsiveness.

Bronchial provocation tests with agents such as histamine and methacholine are commonly used in clinical and epidemiological studies of respiratory illness because bronchial hyperresponsiveness is a non-specific abnormality of the airways which is characteristic of asthma. However, measurements of bronchial responsiveness are log-normally distributed. As a result, special considerations need to be given to reporting within-subject changes in these measurements in longitudinal studies as, for example, in clinical trials or in any study in which a before-and-after experimental design is used. In these types of experiments, changes in bronchial responsiveness should not be simply expressed in the units of the measurement, such as dose of provoking agent, but must be expressed in units based on a logarithmic scale. The appropriate log-based units for measuring within-subject changes are doubling dose, fold difference or percent change. This paper explains the methods for calculating changes in these units in a statistically correct manner. All three units represent different ways of expressing the same change on a logarithmic scale. However, 'doubling dose' is only appropriate when it relates directly to the method of administering the provoking agent in doubling concentrations and 'fold difference' or 'percent change' are both appropriate for expressing any log-based changes. The methods for calculating changes in these units also apply to calculations of repeatability within test methods and to calculations of comparability and agreement between test methods. The methods are described solely for reporting changes in units of bronchial responsiveness but are applicable to other log-normally distributed measurements.

Adult↗

Cloning of hamster osteopontin and expression distribution in normal tissues and experimentally induced oral squamous-cell carcinoma.

Osteopontin (OPN) is a non-collagenous extracellular matrix (ECM) protein expressed and secreted by several human cancers. This study investigated the expression pattern of OPN during development of oral squamous-cell carcinoma by using 7,12-dimethylbenz[a]anthracene (DMBA)-induced squamous-cell carcinomas in buccal pouch of syrian golden hamsters. We first identified the hamster OPN cDNA sequence by screening of a hamster calvariae cDNA library with a rat OPN cDNA probe. The resulting 1,449 bp of hamster OPN cDNA led to a deduced protein sequence of 305 amino acids containing several putative binding sites to integrins, CD44 receptors, calcium ions and hydroxyapatite, as well as multiple sites for phosphorylation, glycosylation and sulphation. Hamster OPN cDNA was then used as a probe to analyze the expression of OPN mRNA by Northern blot and in situ hybridization analyses of normal and malignant tissues. OPN mRNA was detected in several non-mineralized tissues as well as in mineralized tissues, but was not present in normal hamster buccal epithelium. DMBA-treated hamster buccal pouches expressed OPN mRNA as early as 4 weeks and displayed the highest level of expression at 15 weeks. The specimens treated with DMBA for 15 weeks exhibited histological features of squamous-cell carcinoma, presented microcrystalline deposits and showed OPN expression associated with malignant epithelium and tumor-associated macrophages. To summarize, our results suggest that buccal-pouch carcinogenesis of Syrian golden hamster may constitute an excellent experimental model to study the mechanisms by which OPN is associated with oral cancer pathogenesis, and to validate OPN-based therapeutic approaches to ameliorate oral cancer progression and metastasis.

9,10-Dimethyl-1,2-benzanthracene↗

Expression of laminin isoforms by peripheral nerve-derived connective tissue cells in culture. Comparison with epitope distribution in normal human nerve and neural tumors in vivo.

BACKGROUND: Laminins are a family of multifunctional glycoproteins that play a role in various aspects of cell biology. Three different isoforms of laminin have been described, and each comprises a molecule consisting of three subunit polypeptides, the A, B1, B2, M or S chain. EXPERIMENTAL DESIGN: The expression pattern of laminin isoforms was studied by indirect immunofluorescence staining of human peripheral nerve in situ or cell cultures derived from such nerve by using monoclonal antibodies recognizing the subunit epitopes. RESULTS: Selective expression of the subunit polypeptides of laminin isoforms in endoneurium and perineurium was demonstrated. Specifically, an intense immunoreaction for A, B2 and S chain epitopes could be detected in perineurium, whereas endoneurium revealed the presence of B1, B2, M and S chains. Examination of the laminin isoform expression in perineurial cells, Schwann cells, and fibroblasts in cultures derived from normal human nerve indicated, however, that these cells under in vitro conditions were capable of expressing all five laminin chains. Cutaneous neurofibromas, tumors characterized by the presence of mixed cell populations consisting of Schwann cells, perineurial cells, and fibroblasts, demonstrated the expression of B1, B2 and M chain epitopes, whereas only a weak immunostaining could be detected with antibodies recognizing the A and S chains. Similar observations were made on schwannomas, a Schwann cell tumor. CONCLUSIONS: Collectively, the observations of this study attest to the plasticity of neural-derived connective tissue cells with respect to laminin isoform expression. Such plasticity may relate to the cell-cell and cell-matrix interactions during development of peripheral nerves and the potential for neural regeneration.

Adult↗

Neuropsychological function in Tourette syndrome.

The accumulated body of scientific evidence regarding intellectual function, presence of learning disorders, and specific neuropsychological deficits in TS suggests that difficulties in these areas are present in a significant percentage of patients with TS. Despite the numerous methodological shortcomings of past neuropsychological studies of TS, relatively robust and consistent findings have emerged. The literature to date has suggested that intellectual ability is normally distributed in TS. Whether or not individuals with TS have significant discrepancies between their verbal and nonverbal abilities remains unclear. The prevalence of learning disabilities in TS has been reported to be similar to the base rates reported for the general population, although there is evidence to suggest that the prevalence of LDs in children with TS may actually be lower and specific for difficulties in math and written language. Specific cognitive deficits in TS consist of visuomotor integration problems, impaired fine motor skill, and executive dysfunction. The presence of comorbid conditions, notably ADHD and OCD, appears to significantly increase the likelihood that an individual with TS will also have learning problems or some demonstrable cognitive impairment. The presence of a learning disability, specific academic deficiency, or cognitive deficit may pose a greater obstacle for persons with TS than the tic disorder itself. This is particularly salient for children with TS, who may be at a higher risk for poor school performance and academic failure. The psychosocial impact of these problems is also far-reaching. Given the recent emphasis on the early detection of academic and learning problems, it would seem prudent that children with TS who are suspected of having neuropsychological difficulties be evaluated as soon as possible. There are numerous educational interventions and accommodations available to children with LDs and/or specific academic weaknesses that can work equally well in children with TS. The available body of scientific evidence suggests that persons with TS have normally distributed intellectual ability. This would suggest a diminished role for routine IQ testing unless there is compelling clinical evidence to suggest that the IQ score be obtained, such as when the individual is suspected of having an LD. Given that children with TS may be particularly at risk for learning disabilities or academic deficiencies in math and written language, a complete psychoeducational workup should be conducted on any child with TS who is suspected of having such difficulties. This evaluation should be conducted as early as possible, so that educational interventions can be implemented. Traditionally, the psychoeducational evaluation is performed by the school psychologist and should include standardized IQ assessment and academic achievement testing that can objectively identify and quantify the nature and severity of the learning problem. Once the problem has been documented, the school psychologist should recommend appropriate educational and remedial interventions. In addition to psychoeducational testing, neuropsychological testing is indicated to identify specific cognitive deficits that might be present in children with TS, notably problems with visuomotor integration, motor skill, and executive function. The psychoeducational evaluation performed by the school psychologist typically does not assess these cognitive functions. Therefore, referral for neuropsychological testing is indicated if there is a strong clinical suspicion of cognitive deficits. The accumulated neuropsychological literature in TS suggests that a broad-based, comprehensive, and lengthy neuropsychological examination is not necessary, however. At a minimum, the neuropsychological test battery should include assessment of visuomotor integration ability, motor skills, spatial/perceptual abilities, and executive function. This type of assessment would take less time to complete and has greater sensitivity and specificity for identifying neurocognitive deficits that are believed to be unique to TS. Neuropsychological functioning continues to be an important component in understanding the full neurobehavioral spectrum of TS. At present, there is great opportunity to explore neuropsychological functioning in TS with newly emerging technology such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and related techniques that assess cortical metabolic activity, as well as newer electrophysiological techniques. This technology, notably fMRI, allows investigation of neuropsychological functioning in vivo and may reveal important clues to the neuroanatomic substrates of neuropsychological impairment of learning disabilities in TS.

Cognition Disorders↗

Detailed modelling of caffeine metabolism and examination of the CYP1A2 gene: lack of a polymorphism in CYP1A2 in Caucasians.

The cytochrome P450 CYP1A2 is important in the metabolism of both drugs and procarcinogens such as heterocyclic amines. We aimed to clarify the existence of a phenotypic polymorphism and explore the molecular basis of such a polymorphism. Ninety-two non-smoking individuals underwent caffeine phenotyping. The distribution of the 1,7-dimethylxanthine + 1,7-dimethyluracil/caffeine (17U + 17X/137X) ratio and log-transformed data were determined. Probit plots were constructed and the distribution fitted using maximum likelihood method. The CYP1A2 gene, including upstream regulatory regions, was examined for sequence polymorphisms using the single-strand conformation polymorphism technique in 19 individuals and by complete DNA sequencing in two individuals from the extremes of the distribution. We found a similar range (1.45-18.65) and median (6.7) for the 17U + 17X/137X ratio to that found in previous studies of non-smoking Caucasians and no effect of sex. The 17U + 17X/137X ratio gave a normal distribution when log-transformed. Maximum likelihood analysis showed that the log-normal and bimodal distributions had similar deviances but the log-normal distribution was favoured because it has fewer parameters. There was no evidence for significant DNA sequence differences between fast and slow metabolizers, although some differences from published sequences including a silent polymorhpism in exon 7 which were unlikely to be of functional significance were found. We therefore conclude that CYP1A2 does not show functionally significant polymorphism but that the wide interindividual variation in activity may be due to environmental factors.

Adolescent↗

Quinolinic acid in vivo synthesis rates, extracellular concentrations, and intercompartmental distributions in normal and immune-activated brain as determined by multiple-isotope microdialysis.

Quinolinic acid (QUIN) kills neurons by activation of NMDA receptors that are accessed via the extracellular fluid (ECF). In vivo microdialysis was employed to quantify the dynamics of ECF QUIN levels. [(13)C7]QUIN was perfused through the probe for in vivo calibration to accurately quantify ECF QUIN concentrations. Osmotic pumps infused [(2H)3]QUIN subcutaneously to quantify blood contributions to ECF and tissue levels. Local QUIN production rates and influx and efflux rates across the blood-brain barrier were calculated from the extraction fraction of [(13)C7]QUIN, probe geometry, tissue diffusion coefficients, the extracellular volume fraction, and [(2)H3]QUIN/QUIN ratios in blood and dialysates. In normal brain, 85% of ECF QUIN levels (110 nM) originated from blood, whereas 59% of tissue homogenate QUIN (130 pmol/g) originated from local de novo synthesis. During systemic immune activation (intraperitoneal injection of endotoxin), blood QUIN levels increased (10.2-fold) and caused a rise in homogenate (10.8-fold) and ECF (18.5-fold) QUIN levels with an increase in the proportions of QUIN derived from blood. During CNS inflammation (local infusion of endotoxin), increases in brain homogenate (246-fold) and ECF (66-fold) QUIN levels occurred because of an increase in local synthesis rate (146-fold) and a reduction in efflux/influx ratio (by 53%). These results demonstrate that brain homogenate measures are a reflection of ECF concentrations, although there are quantitative differences in the values obtained. The mechanisms that maintain ECF QUIN levels at low values cannot do so when there are large increases in local brain synthesis or when there are large elevations in blood QUIN concentrations.

Administration, Topical↗

Chicken thymocyte-specific antigens identified by monoclonal antibodies: characterization and distribution in normal tissues and in tumoral tissues from Marek's disease chicken.

Monoclonal antibodies (MAbs) were obtained against purified thymocyte membrane extracts. Five MAbs TA3, TB1, TB6 (IgG1), TC4, and TA1 (IgG2a), were tested by immunofluorescence and by immunoperoxidase tests against normal cells from different organs, Marek's disease (MD) cell lines, and MD tumoral cells from chickens. Three of them, TA3, TB1, and TB6, reacted exclusively with lymphoid cells in both cortical and medullary areas of the thymus and with less than 8% bursa cells. They identified a protein of apparently 40 kD. The other two revealed antigenic determinants on most medullar thymocytes and some cortical thymocytes, and on some splenic and peripheral blood lymphocytes. They were positive with MD cell lines and cells deriving from MD tumors. TC4 and TA1 detected molecular masses of about 110 kD and 16 kD, respectively. No MAbs reacted with erythrocytes, bone marrow, liver, brain, and skin cells. Not all of the tested cells were stained after contact with an anti-chicken immunoglobulin serum. In this paper, we determine a specific antigen restricted to T cells from thymus and different markers belonging to the mature T cells. The latter are also present on MD cell lines and MD tumoral cells.

Animals↗

Distribution in normal and inflammatory tissue of a new semisynthetic cephalosporin, SK&F 75073.

SK&F 75073 is a new cephalosporin with broad spectrum antibacterial activity. SK&F 75073-14C and cefazolin-35S were administered separately to groups of rats as a single intramuscular dose of 20 mg/kg. Tissues with highest drug levels 15 minutes following dose were as follows: (SK&F 75073/cefazolin levels), kidney - 86/70 microgram/g, liver - 33/22 microgram/g, lung - 29/17 microgram/g, heart - 23/10 microgram/g, adrenal - 13/7 microgram/g. Plasma levels at peak were 134 microgram SK&F 75073/ml (half-life, 1.9 hours) and 72 microgram cefazolin/ml (half-life, 0.75 hours). Dose excreted in 24 hours was: SK&F 75073, urine 66% and feces 27%; cefazolin, urine 96% and feces 2%. Both antibiotics were also administered, at 20 mg/kg, to rats with the carrageenan-induced inflammatory pouches. Exudate from these pouches contained from 2 to 10 times more SK&F 75073 than cefazolin. Radioassay and bioassay of these substances in the exudate gave similar results. Serum protein binding ranged from 96 approximately 98% for SK&F 75073 and 34 approximately 69% for cefazolin. Data indicated that highly protein bound SK&F 75073 enters tissues and tissue fluid to a greater extent than the lesser bound but therapeutically proven antibiotic agent cefazolin.

Animals↗