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PubMed1979

[Anemia of male rearing calves. Connections between anemia and feed consumption, development of the live weight and disease development].

Calves in a longitudinal investigation over the first rearing period in a rearing farm were grouped according to their anaemic status under consideration of the degree of severity and the duration on the basis of the hemoglobin contents resp. the hematocrit values on the 3rd, 28th and 56th rearing day. There were significant differences between the groups of calves with differing anaemia status concerning the absolute and relative feed consumption (milk, concentrated feed, hay resp. iron), the development of the live weight as well as the frequency of the treatment against pneumonia and/or diarrhoea.

Anemia↗

PubMed1987

Development of B lymphocytes in mice heterozygous for the X-linked immunodeficiency (xid) mutation. xid inhibits development of all splenic and lymph node B cells at a stage subsequent to their initial formation in bone marrow.

CBA/N mice were crossed with CBA/Ca-Pgk-1a to produce female F1 hybrids that were heterozygous for both xid and the phosphoglycerate kinase 1 (PGK-1) allozymes. PGK acted as a quantifiable marker for the frequency of cells in which the xid-bearing X chromosome was active in lymphocytic and other cell populations. In adults, such cells (termed xid cells) were virtually absent in FACS-sorted splenic and lymph node B cells, and in all three splenic subpopulations distinguished on the basis of their relative expression of membrane mu and delta chains. Thus, the xid mutation appeared to compromise the development of all B cells. Erythrocytes, thymocytes, T cells, and granulocytes were unaffected. Selection against xid cells was less pronounced in the spleens of 2-6-wk-old mice. In the bone marrow, there was evidence for selection against xid in the production of B cells (except at 2 wk of age), but not at the pre-B cell level. These data suggest that, in competition with normal non-xid cells, newly-formed xid B cells were less likely to be incorporated into the peripheral B cell pool.

Animals↗

PubMed2004

Development of biomarkers based on diet-dependent metabolic serotypes: practical issues in development of expert system-based classification models in metabolomic studies.

Dietary restriction (DR)-induced changes in the serum metabolome may be biomarkers for physiological status (e.g., relative risk of developing age-related diseases such as cancer). Megavariate analysis (unsupervised hierarchical cluster analysis [HCA]; principal components analysis [PCA]) of serum metabolites reproducibly distinguish DR from ad libitum fed rats. Component-based approaches (i.e., PCA) consistently perform as well as or better than distance-based metrics (i.e., HCA). We therefore tested the following: (A) Do identified subsets of serum metabolites contain sufficient information to construct mathematical models of class membership (i.e., expert systems)? (B) Do component-based metrics out-perform distance-based metrics? Testing was conducted using KNN (k-nearest neighbors, supervised HCA) and SIMCA (soft independent modeling of class analogy, supervised PCA). Models were built with single cohorts, combined cohorts or mixed samples from previously studied cohorts as training sets. Both algorithms over-fit models based on single cohort training sets. KNN models had >85% accuracy within training/test sets, but were unstable (i.e., values of k could not be accurately set in advance). SIMCA models had 100% accuracy within all training sets, 89 % accuracy in test sets, did not appear to over-fit mixed cohort training sets, and did not require post-hoc modeling adjustments. These data indicate that (i) previously defined metabolites are robust enough to construct classification models (expert systems) with SIMCA that can predict unknowns by dietary category; (ii) component-based analyses outperformed distance-based metrics; (iii) use of over-fitting controls is essential; and (iv) subtle inter-cohort variability may be a critical issue for high data density biomarker studies that lack state markers.

Algorithms↗

PubMed2006

Associations of serum carotenoid concentrations with the development of diabetes and with insulin concentration: interaction with smoking: the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Smoking is associated with low serum carotenoid concentrations. Prospective studies have found lower diabetes risk among persons with high-carotenoid diets. Whether diabetes risk is low in the rare smoker who has high serum carotenoid levels is unknown. The authors investigated the interaction of serum carotenoid concentrations and smoking with diabetes mellitus in 4,493 Black and White men and women aged 18-30 years in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. The authors assessed 15-year (1985-2001) incident diabetes (148 cases), insulin concentration, and insulin resistance (homeostasis model assessment) in smokers and nonsmokers according to baseline levels of serum alpha-carotene, beta-carotene, zeaxanthin, beta-cryptoxanthin, and lycopene. Diabetes incidence was inversely associated with the sum of carotenoid concentrations in nonsmokers (per standard deviation (SD) increase, relative hazard = 0.74, 95% confidence interval: 0.55, 0.99) but not in current smokers (relative hazard = 1.13, 95% confidence interval: 0.83, 1.53) (p for interaction = 0.02). Similarly, year 15 insulin and insulin resistance values, adjusted for baseline levels, were inversely related to sum of carotenoids only in nonsmokers (per SD increase in insulin level, slope = -0.46 (p = 0.03); per SD increase in insulin resistance, slope = -0.14 (p = 0.01)). In CARDIA, higher serum carotenoid concentrations are associated with lower risk of diabetes and insulin resistance in nonsmokers but not in smokers.

Adolescent↗

PubMed2003

Continuing professional development (CPD): GPs' perceptions of post-graduate education-approved (PGEA) meetings and personal professional development plans (PDPs).

BACKGROUND: Conventional post-graduate meetings-typically 'lunchtime' meetings outside practices-have been heavily criticized. Revalidation is also impending, and there has been associated pressure for the widespread introduction of personal development plans (PDPs). However, there is very little empirical evidence about the usefulness to GPs of different kinds of educational meeting or of PDPs. OBJECTIVES: Our aim was to assess the utility to GPs of different types of post-graduate meeting and PDPs. METHODS: A postal questionnaire was sent to 921 GP principals in three health authorities, who were asked to recall their most recent post-graduate education-approved (PGEA) meetings (practice-based and 'outside') and the latest major learning 'undertaken' in their PDP. RESULTS: A total of 698 GPs (76%) returned questionnaires. A substantial minority (208; 30%) had a PDP. Most had undertaken education recently [median time elapsed (weeks): meeting 'outside' practice, 4; 'practice-based', 5; PDP, 3]. Education had not changed clinical practice for many GPs ('practice-based' 39% reported no change; 'outside' meetings 50% and PDPs 57%). A change in practice after a practice meeting was related to relevance to everyday practice [disagree/neutral, agree, strongly agree odds ratios: 1.00, 4.22 (95% CI 2.1-8.6) and 5.9 (2.6-13.3), respectively], to lecturer factors (enthusiasm, summarizing important points, handouts) and to social enjoyment. PDPs were less likely to be perceived relevant to practice (practice-based meeting, 'outside' meeting, PDPs: 89, 87 and 72%, respectively), as a break from practice (54,72 and 18%), good socially (63, 72 and 15%), good for professional networking (54, 70 and 19%) and glad to have done it (84, 86 and 44%). Being glad to use a PDP was more likely if the learning was clinically relevant, a break from practice, and incorporated professional networking. CONCLUSION: Changes in practice after post-graduate meetings are not only related to clinical relevance and lecturer factors, but also to professional and social factors. PDPs may not be providing better learning opportunities or enjoyment than traditional meetings, although GPs who are glad to use PDPs incorporate clinical relevance, a break from practice and networking. Post-graduate tutors should probably continue to support and monitor the lecturer quality and clinical relevance of a balanced portfolio of both practice-based and 'outside' meetings.

Adult↗

PubMedDate not supplied

Recombinant follicle stimulating hormone: development of the first biotechnology product for the treatment of infertility. Recombinant Human FSH Product Development Group.

Genes encoding the common gonadotrophin alpha subunit and follicle stimulating hormone (FSH)-specific beta subunit were isolated from a DNA library derived from human fetal liver cells, and inserted into separate expression vectors containing a selectable/amplifiable gene. These vectors were inserted into the genome of the Chinese hamster ovary cell line, resulting in expression of large amounts of biologically active human (h)FSH. This cell line was cultured on microcarrier beads in a large-scale bioreactor. hFSH in the cell culture supernatant was purified to homogeneity by a multistep process. The mature beta subunit had seven fewer amino acid residues than reported in the literature and three other differences were found in the sequence. Similar oligosaccharide structures were present on recombinant (r)-hFSH and a purified urinary (u)-hFSH preparation. In-vitro and in-vivo, the biological activities of u- and r-hFSH were indistinguishable. r-hFSH was formulated in ampoules containing 75 IU FSH activity (approximately 7.5 microg FSH), which accounts for >99% of the protein content of the preparation. Studies in non-human primates and human volunteers showed the pharmacokinetics of u- and r-hFSH to be similar. In healthy volunteers, r-hFSH stimulated follicular development and induced significant increases in serum oestradiol and inhibin. Clinical experience with r-hFSH has shown it is more effective at stimulating ovarian follicle growth than urinary gonadotrophins. It is also effective at initiating spermatogenesis when given together with human chorionic gonadotrophin.

Animals↗

PubMed2006

Oncogene 6b from Agrobacterium tumefaciens induces abaxial cell division at late stages of leaf development and modifies vascular development in petioles.

The 6b gene in the T-DNA region of the Ti plasmids of Agrobacterium tumefaciens and A. vitis is able to generate shooty calli in phytohormone-free culture of leaf sections of tobacco transformed with 6b. In the present study, we report characteristic morphological abnormalities of the leaves of transgenic tobacco and Arabidopsis that express 6b from pTiAKE10 (AK-6b), and altered expression of genes related to cell division and meristem formation in the transgenic plants. Cotyledons and leaves of both transgenic tobacco and Arabidopsis exhibited various abnormalities including upward curling of leaf blades, and transgenic tobacco leaves produced leaf-like outgrowths from the abaxial side. Transcripts of some class 1 KNOX homeobox genes, which are thought to be related to meristem functions, and cell cycle regulating genes were ectopically accumulated in mature leaves. M phase-specific genes were also ectopically expressed at the abaxial sides of mature leaves. These results suggest that the AK-6b gene stimulates the cellular potential for division and meristematic functions preferentially in the abaxial side of leaves and that the leaf phenotypes generated by AK-6b are at least in part due to such biased cell division during polar development of leaves. The results of the present experiments with a fusion gene between the AK-6b gene and the glucocorticoid receptor gene showed that nuclear import of the AK-6b protein was essential for upward curling of leaves and hormone-free callus formation, suggesting a role for AK-6b in nuclear events.

Agrobacterium tumefaciens↗

PubMed1997

Comparison of embryos and chicks that developed as single individuals in double yolk eggs with those that developed in single yolk eggs.

Body weight and muscle characteristics of 18- to 20-d-old broiler strain embryos developing in double yolk eggs (DY) that contained one embryo and one infertile ovum were compared with embryos in single yolk eggs (SY). Similar comparisons were made in the posthatching period. In some DY eggs, the embryos were bathed in a watery yolk-like fluid with no distinct second yolk present (Type 1 embryo). In others, the second yolk was contained within the vitelline membrane and surrounded by a vascularized membrane (Type 2). These embryos were heavier than Type 1 or embryos in SY eggs by 20 d of incubation. Their Pectoralis superficialis were heavier and had significantly more protein and DNA. Chicks that hatched from the DY eggs were heavier than those that hatched from SY eggs and they had heavier P. superficialis through at least 14 d of age. Pectoralis superficialis myofibers of chicks from DY eggs had greater cross-sectional area than those from SY eggs. Myofibers in the Semimembranosus of 7- and 14 d-old chicks from DY eggs tended to be larger than those from SY eggs, but the differences were not significant. There was no difference in apparent myofiber number in the Semimembranosus of the two types of chicks. The difference in BW between the two types of chicks diminished over time, so that by 42 d of age they were virtually identical. In summary, a nutritionally enriched in ovo environment resulted in embryos and chicks with enhanced growth and muscle mass, but the effects of enrichment diminished during posthatching life and eventually disappeared.

Animals↗

PubMed1998

Abnormalities in functional development of the Sertoli cells in rats treated neonatally with diethylstilbestrol: a possible role for estrogens in Sertoli cell development.

Diethylstilbestrol (DES) was administered neonatally (Days 2-12; 10 microg on alternate days) to rats, and developmental changes in Sertoli cell function were evaluated at 18, 25, and 35 days of age and compared to those observed in rats administered a GnRH antagonist (GnRHa; Days 2 and 5; 10 mg/kg) or a vehicle (controls). DES and GnRHa treatments resulted in similar reductions in both Sertoli cell numbers (40% for DES, 48% for GnRHa) and suppression of testicular growth at 18 and 25 days, though by 35 days the suppression was more pronounced (p < 0.001) in DES-treated animals. Plasma FSH levels were suppressed markedly at 18 and 25 days, but not at 35 days, in GnRHa-treated rats, whereas in DES-treated rats the FSH levels were suppressed significantly only at 35 days. Both treatments suppressed plasma levels of inhibin B, though this was more pronounced (p < 0.05) in DES- than in GnRHa-treated rats. In controls, Sertoli cell immunoexpression of inhibin alpha, sulfated glycoprotein-1 (SGP-1), and androgen receptor (AR) increased in intensity and changed to an adult, stage-dependent pattern by 25 days. In GnRHa-treated rats these changes were reduced in intensity but were similar to those in controls at 35 days. In DES-treated rats, the increase in intensity and stage-dependent pattern of immunoexpression of inhibin alpha, SGP-1, and AR were virtually absent at 25 days but were present by 35 days. Germ cell volume per Sertoli cell was reduced in GnRHa- and DES-treated rats compared with controls at 18 and 25 days but was significantly greater (p < 0. 001) in DES- than in GnRHa-treated rats at 35 days. The proportion of apoptotic to viable germ cells was increased (p < 0.01) in GnRHa- and DES-treated rats compared with controls at 18 and 25 days; but at 35 days, values in GnRHa-treated rats had declined to control values whereas those for DES-treated rats remained 10-fold elevated (p < 0.001). In adulthood, testis weight and daily sperm production were reduced by 43% and 44%, respectively, in GnRHa-treated rats, but spermatogenesis was grossly normal. Comparable changes were observed in approximately 25% of DES-treated rats, but the majority exhibited > 60% reduction in testis weight with many Sertoli cell-only tubules and very low daily sperm production. Taken together, these data are interpreted as providing evidence for direct modulation of Sertoli cell (maturational) development by DES.

Aging↗

PubMed1972

Studies on Chloroplast Development and Replication in Euglena: III. A Study of the Site of Synthesis of Alkaline Deoxyribonuclease Induced during Chloroplast Development in Euglena gracilis.

During chloroplast development in Euglena, the activity of a specific DNase, Euglena alkaline DNase, increases in a manner similar to that of chlorophyll synthesis, but without the lag customarily associated with the early hours of chlorophyll synthesis. The increase in Euglena alkaline DNase activity is not inhibited by chloramphenicol or by streptomycin, but is inhibited by cycloheximide. Euglena alkaline DNase activity is present in a group of aplastidic substrains which contain carotenoids. These results are interpreted to mean that this chloroplast-related DNase is synthesized in the cytoplasm, and that the genetic information for this enzyme is probably nuclear.It is also shown that different bleached substrains exhibit substantial variation, both in total carotenoids and in Euglena alkaline DNase activity. These results are discussed in terms of the possibility that a cytoplasmic photoreceptor system is influencing the light-induced increase in Euglena alkaline DNase activity.

Journal Article↗

PubMed1973

Biochemical Studies on Development of Mitochondria in Pea Cotyledons during the Early Stage of Germination: Effects of Antibiotics on the Development.

l-Leucine-U-(14)C was incorporated into mitochondrial protein in pea (Pisum sativum var. Alaska) cotyledons during the imbibing stages. Incorporation was almost completely inhibited by cycloheximide but not by chloramphenicol. Both antibiotics did not affect increases in mitochondrial activities and components of the cotyledons during imbibition. Therefore, mitochondrial development seems to be achieved by a transfer of protein pre-existing in the cytoplasm into the mitochondria rather than by de novo synthesis of mitochondrial protein. Cycloheximide stimulated an increase in bile saltsoluble protein of mitochondria in imbibing pea cotyledons. The recovery of cytochrome oxidase activity after sucrose density gradient centrifugation was enhanced, and the morphological properties of mitochondria were altered by cycloheximide.

Journal Article↗

PubMed1976

The development of apparatus for intermittent negative pressure respiration. (2) 1919-1976, with special reference to the development and uses of cuirass respirators.

This paper and the one that preceded it1 have traced the development of the design and use of negative pressure ventilators from their origins in the early nineteenth century to the present day. Their maximum use was in the nineteen-forties and the early fifties after which they were quite rapidly replaced in the treatment of acute respiratory disease by intermittent positive pressure ventilators-the turning point being the severe poliomyelitis epidemic in Copenhagen in 1952. Negative pressure ventilators, particularly cuirass ventilators, still have a place in the treatment of chronic respiratory disease.

Australia↗

PubMed1994

Development of the long-term medication behaviour self-efficacy scale: qualitative study for item development.

There are no published instruments of patient self-efficacy related to medication behaviour, yet understanding and promoting medication compliance are central to nursing practice. The purpose of this quanlitative study was to explore patient perceptions, experiences and practices associated with long-term medication behaviour in order to establish an instrument measuring self-efficacy in medication behaviour. In-depth interviews were conducted with 14 patients with lifelong dependency on medicine. Using a phenomenological method of analysis the following themes emerged, all of which could be integrated within Bandura's conceptualization of dimensions of self-efficacy. The dimension of personal attributes comprised the themes of emotional distress, confidence in the physician, perceived health status, and normalcy. Environmental factors included the themes of routine, distraction, social support and cost of medication. The third dimension of self-efficacy, task-related and behavioural factors was composed of themes of side-effects, drug delivery system, medication aids, medication schedule, and knowledge. Based on these themes, items for the Long-Term Medication Behaviour Self-Efficacy Scale, were developed and integrated into a version that is currently being submitted to further psychometric work.

Adult↗

PubMed1997

Development of hippocampal atrophy: a serial magnetic resonance imaging study in a patient who developed epilepsy after generalized status epilepticus.

PURPOSE: To investigate changes in hippocampal volume. METHODS: We used serial magnetic resonance imaging (MRI) in a patient who developed chronic epilepsy after having generalized tonic-clonic status epilepticus (SE). Five MRI investigations were performed during SE and a 58-month follow-up period. Hippocampal volumetric measurements and coregistration of scans were performed to detect hippocampal atrophy. RESULTS: During status both mesiotemporal regions returned a high signal on T2-weighted images. Two months after the onset of SE, bilateral hippocampal atrophy was detected. Further progressive hippocampal atrophy was detected in the subsequent 58 months by both hippocampal volumetric measurements and coregistration of scans. CONCLUSIONS: Our findings suggest that hippocampal atrophy is a process that may continue after the end of the SE.

Adult↗

PubMed2003

Faculty development: what is faculty development?

Faculty development is an organized, goal-directed process to achieve career progression and growth. Inherent in this process is the acquisition of skills that enable one to contribute in a meaningful way to the advancement of a field of interest, whether educational, operational, or scientific. The process requires attention to technical skills, personal attributes, and explicit goals. Supportive mentorship is optimal. This document outlines important concepts and identifies helpful resources for academic faculty members. Additional resources are available at http://www.saem.org/facdev/index.htm.

Education, Medical↗

PubMed1995

Development of a microtitre ELISA to quantify development of Cryptosporidium parvum in vitro.

An in situ enzyme-linked immunosorbent assay (ELISA) was developed to evaluate growth of Cryptosporidium parvum in vitro. Ninety-six-well tissue culture microtitre plates were each seeded with 4.0 x 10(4) human ileocecal adenocarcinoma (HCT-8) cells, then infected with CsCl-purified oocysts 24 h later. The growth medium consisted of RPMI 1640 supplemented with 10% fetal bovine serum, 15 mM HEPES (N-2-hydroxyethylpiperazine N'-2-ethanesulfonic acid), 50 mM glucose, 1 microgram ml-1 folic acid, 4 micrograms ml-1 4-aminobenzoic acid, 2 micrograms ml-1 pantothenic acid and 35 micrograms ml-1 ascorbic acid. Incubation conditions were at 37 degrees C in a 5% CO2/95% humidified air incubator. Oocysts were allowed to excyst in situ so that sporozoites could infect cells directly. Monolayers were then washed, new medium added, and infected cells re-incubated. Levels of infection were assessed 48 h later using a rat anti-C. parvum polyvalent antiserum directed against purified parasite membranes, followed by a goat anti-rat IgG conjugated to horseradish peroxidase and 3,3',5,5'-tetramethyl-benzidine as substrate. Using various parasite inoculating doses and incubation times, optimal results were obtained using a 90-min exposure of host cells to 2.5-3.0 x 10(4) oocysts/well. Evaluation of various concentrations of four anti-microbials (monensin, lasalocid, paromomycin and sulfadimethoxine) in the system resulted in the acquisition of precise dose-response curves for each compound.

Animals↗

PubMed1997

Do root lesions tend to develop in the same people who develop coronal lesions?

OBJECTIVES: The three purposes of this study are to: (1) describe the relationship between the prevalence of coronal caries and root caries; (2) describe the relationship between the three-year incidence of coronal caries and root caries; and (3) if the two conditions are associated, develop a multiple regression model that identifies characteristics distinguishing people who had increments of both root caries and coronal caries from people who had increments of either coronal caries or root caries, or who had no new caries. METHODS: Dental examinations and interviews were conducted in the homes of a randomly selected, stratified sample of people over the age of 65 years in five North Carolina counties. The relationships between coronal and root D and DF were analyzed through contingency table analyses, and ordinal logistic regression was used to identify characteristics that differentiated people who had both coronal and root D over the three years from people who had either coronal or root D and people who had no new disease. RESULTS: Evidence of root and coronal caries in whites was much more likely to be in the form of fillings, while for blacks, it was more likely to be in the form of untreated decay. Prevalence rates of coronal and root D and DF were significantly associated for both blacks and whites. Incidence rates based on DF indicated that root and coronal caries were not associated in whites, but were associated in blacks. People more likely to experience both types of caries had more gingival recession at baseline, greater average attachment loss over the three years, and lactobacilli at baseline. In addition, the presence of Porphymonas gingivalis at three years was important for whites. CONCLUSIONS: It appears that coronal and root caries do tend to appear together in the same individuals, but fillings attenuate that relationship. The impact of dental treatment on the epidemiology of dental caries appears to be considerable and calls into question whether the F component of the caries index is related to disease as defined by epidemiologic criteria.

Aged↗

PubMed1986

Development of auditory-evoked potentials in the cat. I. Onset of response and development of sensitivity.

Auditory-evoked potentials, originating from the brain stem and the forebrain, were studied in 30 unanesthetized kittens during the first 3 months of postnatal life, and from a smaller set of animals before and after surgical exposure of their tympanic membranes. In intact animals, responses to 135-dB peak SPL clicks were first reliably discernible on the seventh postnatal day; when stimuli were presented directly to the exposed tympanic membrane, responses were observed several days earlier. Responses progressed through three stages during maturation: an early period of gross insensitivity during which responses are evoked only by high-intensity stimuli and whose response thresholds remain essentially constant (week 1); a middle period characterized by rapid acquisition of sensitivity to near-adult values (week 2); and a late period during which adult thresholds and latencies are acquired. A sequential stage model of threshold maturation is proposed, in which thresholds decline linearly during stage two and exponentially during stage three. It is hypothesized that mechanical reorganization of the cochlea during the first 2 to 3 postnatal weeks and development of the stria vascularis are primarily responsible for the linear stage, and that neural factors primarily underlie the exponential stage and account for the gradual acquisition of adult thresholds. Rates of maturation for brain stem responses are frequency dependent, with responses to high frequencies achieving adult thresholds earlier than those to low frequencies.

Aging↗