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PubMed1997

Terminal differentiation of human germinal center B cells in vitro.

In order to define an in vitro culture system allowing growth of single human germinal center B cells (GC-B), we have studied the proliferation and differentiation of human tonsillar GC-B, and subsets thereof, when cultured together with murine EL-4 thymoma cells in the "EL-4 system." The cells were analyzed and compared to resting tonsillar B cells with respect to phenotypic changes, proliferation, Ig secretion, intracellular Ig levels, and growth abilities under limiting dilution conditions. It was found that GC-B differentiated terminally to Ig-secreting cells with the phenotypic features of plasma cells in a similar manner to tonsillar resting B cells. The GC-B proliferated for 4-5 days, followed by a loss of GC-B phenotype and an increase in intracellular immunoglobulin levels. Over a 10-day culture period a larger proportion of the Ig produced by GC-B was IgG and IgA, as compared to resting B cells, indicating that these cells switched isotype more easily or had already switched in the germinal center prior to the culture period. Analysis of frequencies of Ig-producing cells revealed that 1/3.8 of GC-B and less than 1/10 of the centroblast B cell subpopulation (CB-B) differentiated toward Ig-producing cells when cultured in the EL-4 system whereas 1/1.25 and 1/1.5 of peripheral blood B cells (PBL-B) and resting tonsillar B cells did so, respectively. Taken together, these findings show that tonsillar GC-B differentiate in a similar manner to resting B cells when cultured in the EL-4 system, and we conclude that these conditions allow manipulation of GC-B in single cell cultures in vitro.

Animals↗
PubMed1997

Relation between pro- and anti-inflammatory cytokines and the production of nitric oxide (NO) in severe sepsis.

The aim of the present study was to investigate the relationship between the levels of pro-inflammatory [interleukin 6 (IL-6), IL-8, tumour necrosis factor alpha (TNF-alpha)], anti-inflammatory cytokines [IL-10, soluble TNF receptor type I (TNFsrI), TNFsrII], and the production of nitric oxide (NO) during a 1-week period in 23 patients with severe sepsis. The highest levels of pro-inflammatory cytokines and nitrate, the stable metabolite of NO, were found during the first day after inclusion and gradually declined thereafter. Detectable levels of IL-10, TNFsrI and TNFsrII were present in all patients at study entry but did not significantly change during the study period [analysis of variance (MANOVA); P > 0.05]. Serum nitrate levels correlated significantly with both pro-inflammatory cytokines (IL-6, IL-8, TNF-alpha) as well as anti-inflammatory cytokines (IL-10, TNFsrI, TNFsrII). Serum nitrate levels over time were higher in patients with positive blood cultures (n = 4) (MANOVA; P < 0.005), as compared to patients without proven bacteraemia. These data support the concept of an acute phase of sepsis that is characterized by an excess of pro-inflammatory cytokines, while anti-inflammatory cytokines are predominantly present during the secondary phase. The present findings indicate that pro-inflammatory cytokines are related to the induction of excessive NO production during the first phase of sepsis and that reduction of NO production occurs during the secondary phase. This may suggest that anti-inflammatory cytokines are able to diminish the production of NO in patients with severe sepsis.

Antigens, CD↗
PubMed1994

Biotreatment of ammonia- and butanal-containing waste gases.

The biological removal of ammonia and butanal in contaminated air was investigated by using, respectively, a laboratory-scale filter and a scrubber-filter combination. It was shown that ammonia can be removed with an elimination efficiency of 83% at a volumetric load of 100 m3.m-2.h-1 with 4-16 ppm of ammonia. During the experiment percolates were analysed for nitrate, nitrite, ammonium and pH. It was found that the nitrification in the biofilter could deteriorate due to an inhibition of Nitrobacter species, when the free ammonia concentration was rising in the percolate. It should be easy to control such inhibition through periodic analysis of the liquid phase by using a filter-scrubber combination. Such a combination was studied for butanal removal. Butanal was removed with an elimination efficiency of 80% by a scrubber-filter combination at a volumetric load of 100 m3.m-2.h-1 and a high butanal input concentration. Mixing the filter material with CaCO3 and pH control of the liquid in the scrubber resulted in an increase of the elimination efficiency. These results, combined with previous results on the biofiltration of butanal and butyric acid, allow us to discuss the influence of odour compounds on the removal efficiency of such systems and methods for control. The results were used to construct a full-size system, which is described.

Air Pollutants↗
PubMed1996

Temporal coding in vision: coding by the spike arrival times leads to oscillations in the case of moving targets.

The 'oscillations' which have been observed in the visual cortex of cats and monkeys in the case of moving targets are discussed in relation to a temporal coding based on the arrival times of spikes or bursts. A decoding process for this temporal coding is proposed in which neurons work in a correlator mode. In the case of motion analysis, periodic resetting is needed to avoid information jamming. This resetting is proposed to be responsible for the 'oscillations'. Good initial synchronization is required for the decoding process to be performed efficiently. A diffusive process based on interdendritic ionic currents is proposed and shown to operate efficiently, without any loss of spatial and temporal resolving powers.

Animals↗
PubMed1988

Work at sea: a study of sleep, and of circadian rhythms in physiological and psychological functions, in watchkeepers on merchant vessels. III. Rhythms in physiological functions.

Oral and rectal temperature, urinary excretion of adrenaline and noradrenaline, and heart rate were measured in 28 watchkeepers working a "4-on/8-off" routine, and in 25 dayworkers, on board ships. Readings of oral temperature were taken over 4-hourly periods of up to two weeks; the rectal temperature, urine, and heart rate data were collected on selected days within these periods. Analysis of watchkeepers' temperatures and unconjugated catecholamine excretions showed slight signs of an interactive adaptation to time of day and hours of work, but it was clear that full phase adjustment of the circadian rhythms to shifted hours of work did not occur. The "split" pattern of sleep imposed by the watch system may be a major factor in preventing complete adaptation of physiological rhythms to shift work in the shipboard situation; this problem could be overcome by devising a system that allows sleep to be taken in a single uninterrupted block each day.

Body Temperature↗
PubMed1983

Clinical investigations into antidepressive mechanisms. I. Antihistaminic and cholinolytic effects: amitriptyline versus promethazine.

It is assumed that established antidepressants exert their clinical efficacy by potentiation or decrease of central noradrenergic and serotonergic neurotransmission. However, recent experimental work suggests that antihistaminic and/or cholinolytic effects may also be involved. This double-blind controlled study compared amitriptyline (catecholamine potentiating, antihistaminic, cholinolytic) with promethazine (antihistaminic, cholinolytic) in 50 severely depressed inpatients over a 30-day treatment period. Analysis of the Hamilton depression rating scale revealed significant clinical superiority of amitriptyline over promethazine in such major depressive symptoms as depressed mood, suicidal ideation, psychic anxiety, and sleep disturbances. No significant difference was evident as far as autonomous side effects were concerned. Similar results were found by analysis of the AMP rating system. It is concluded that antihistaminic or cholinolytic effects per se do not explain the antidepressants' efficacy. However, potentiation of noradrenergic neurotransmission by cholinolytic activity might be the major antidepressive mechanism.

Adult↗
PubMed1978

Increased clinic awareness and attitudes of independence through client advisory board membership.

In order to determine the effect of client advisory board membership on clients' awareness of a clinic, and on client attitudes of independence, the responses of 13 board members were compared with those of 13 matched controls on two self-report measures (Clinic Recognition Test, Client Independence Questionnaire) before and after 3-month periods. Analysis of the results indicated that, whereas the responses of controls did not significantly change on the Client Independence Questionnaire, the responses of board members indicated a significant increase in attitudes of independence. And, even though both board members and control clients significantly increased their awareness of clinic and staff over 3 months, the awareness of the broad members was significantly greater than that of the control clients.

Adult↗
PubMed1980

Clovoxamine and fluvoxamine-2 biogenic amine re-uptake inhibiting antidepressants: quantitative EEG, psychometric and pharmacokinetic studies in man.

In a double-blind placebo-controlled study, the encephalotropic, psychotropic, pharmacodynamic and pharmacokinetic properties of 2 new substances, clovoxamine (a 5-HT and NE re-uptake inhibitor) and fluvoxamine (a selective 5-HT inhibitor) were investigated utilizing quantitative pharmaco-EEG, psychometric and blood level analyses. Ten normal volunteers received randomized and in weekly intervals oral single doses 50 mg, 75 mg and 125 mg clovoxamine, 75 mg fluvoxamine, placebo and as reference drug 75 mg imipramine. Quantitative EEG, psychometric data, pulse, blood pressure, side effects and pharmacokinetic data were studied at the hours 0, 2, 4, 6 and 8. Plasma levels of both substances peaked in the 4th to 6th hour and declined slowly thereafter. Digital computer period analysis of the EEG demonstrated after clovoxamine only minor changes characterized by an increase of fast beta-activities suggesting slight activating qualities of the drug. On the other hand 75 mg fluvoxamine and especially 75 mg imipramine produced marked CNS changes characterized by a concomitant increase of slow and fast activities and a decrease of alpha-activity. However, 75 mg fluvoxamine induced less augmentation of slow activity than imipramine indicating less sedative properties of fluvoxamine than the standard reference drug. Psychometric tests demonstrated after 50 and 75 mg clovoxamine and 75 mg fluvoxamine an increase in attention, attention variability, concentration, CFF and after-effect in the Archimedean Spiral (indicating central activation), further an improvement in mood and affectivity as compared with placebo, while 125 mg clovoxamine and 75 mg imipramine produced an increase in reaction time, deterioration of mood and affect and psychomotor activity. The latter changes were observed also after other antidepressants in normals. Pharmacodynamic investigations regarding dose-efficacy and time-efficacy relations based on both EEG and psychometric parameters revealed that 75 mg imipramine was the most effective compound, followed by 75 mg fluvoxamine and 125 mg, 75 mg and 50 mg clovoxamine. The peak effect of clovoxamine and fluvoxamine was observed around the 6th hour, while 75 mg imipramine was maximally observed around the 6th hour, while 75 mg imipramine was maximally effective between the 2nd and the 4th hours. Side effects were minimal after clovoxamine (interestingly euphoria in 3 subjects), while tiredness was seen in 5 out of 10 subjects after 75 mg fluvoxamine and in 8 out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.

Adult↗
PubMed1992

Naturally occurring-neutralizing monoclonal antibody escape variants define the epidemiology of infectious bursal disease viruses in the United States.

A panel of two non-neutralizing and six neutralizing monoclonal antibodies (Mabs) were used in antigen-capture enzyme immunoassays (AC-ELISA) to examine the antigenicity of 1301 wild type infectious bursal disease viruses (IBDV) isolated from different poultry flocks throughout the United States over a three year period. Analysis of these isolates with protective, neutralizing Mabs directed against the VP2 structural protein of IBDV showed that four antigenically distinct groups of serotype 1 IBDV could be separated on the basis of the presence or absence of one or more Mab defined, conformation-dependent, multivalent neutralization site. AC-ELISA reactivity patterns of the Mabs with isolates demonstrated that IBDV field populations were relatively antigenically homogeneous per premise isolation. Geographically, various antigenic species were more or less prevalent, or nearly absent. Competition analysis with neutralizing Mabs coupled with AC-ELISA results suggested that neutralization epitopes for IBDV are distinct, spatially arranged, yet closely linked. Of 5 Mab defined neutralization epitopes, shown to be related to protection from virulent challenge by Classic IBDV strains isolated prior to 1985, only two of the epitopes remain unaltered on the most recent emergent variant field strain of IBDV isolated.

Animals↗
PubMed1987

A stomach oncofetal antigen recognized by monoclonal antibody GC302.

A monoclonal antibody, GC302, was established by fusing murine myeloma NS/1 cells with the splenocytes of a BALB/c mouse immunized with a human gastric cancer cell line, NU-GC-3. The serological specificity of GC302 was analyzed by an anti-mouse Ig mixed-hemadsorption (MHA) test on a panel of human cell lines, and an immunoperoxidase method using the frozen sections of tumors and normal tissues of adult and fetus. GC302 reacted with cancers of the stomach and colorectum but did not react with hepatocellular carcinomas, melanomas, or astrocytomas in the MHA tests. By the immunoperoxidase method, GC302 was found not to react with normal adult gastric mucosa, but to react with the mucosa in the fetal stomach, intestinal metaplasia, and almost all of the cancer of the stomach. GC302 also reacted with the normal mucosa of the intestine, colon, and rectum as well as with cancers of these origins. In normal liver sections, the antibody reacted with the bile ducts, but not with the hepatic cells. These results indicate that the antigen detected by GC302 is characterized as an oncofetal antigen in the stomach, and also as a differentiation antigen whose localization discriminates between the gastrointestinal tracts of the forgut origin and those of the midgut and hindgut origin. The molecular weight of the GC302 antigen was estimated to be ca. 40,000 by the Western blot analysis. Periodic acid treatment on the antigen suggested that the antigenic determinant is a carbohydrate.

Animals↗
PubMed1990

Explaining first marriage trends in Australia.

"This paper presents new estimates of Australian first marriage trends since the 1920s and then focuses on the recent period. Analysis of first marriage statistics shows that nuptiality decline actually began amongst the oldest potential marriers in the late 1960s, and then percolated down to the younger ages. An attempt to explain recent trends through Becker's economic theory of marriage proves unsuccessful. Nevertheless, time-series regression analyses indicate that over the last twenty years first marriage rates in Australia have followed major movements in economic factors, in particular employment status, and that neither normative change nor the economic rationality postulated by the economic theory of marriage needs to be invoked as the primary determinant of changing nuptiality."

Age Factors↗
PubMedDate not supplied

Disposition of a new rate-controlled formulation of prazosin in the treatment of hypertension during pregnancy: transplacental passage of prazosin.

Prazosin (PRZ) in conventional tablet form (P-CT) has the disadvantages of a relatively short terminal half-life, a slight solubility in water and the well-recognized adverse effect of symptomatic orthostatic hypotension. The pharmacokinetic study of a new rate-controlled formulation of prazosin (Prazosin-Gastrointestinal System: P-GS) was performed in 9 pregnant women during the third trimester of pregnancy. Patients had persistent elevation of blood pressure. The subjects gave their informed consent for oral administration of 1 daily dose of 5 mg P-GS at 8 a.m. A first analysis period on day 1 enabled definition of the initial pharmacokinetic behavior of the drug, while the aim of a second was to evaluate its fate at plateau. The clinical course of both mother and fetus was subsequently monitored. This was an open, non-randomized study, each patient serving as her own control. For 3 patients, we aimed to determine the possible transplacental passage of PRZ at delivery. PRZ levels were measured by HPLC and data were analysed by noncompartmental linear pharmacokinetic methods. The data show: (i) P-GS was well tolerated by all patients and there were no significant changes in fetal heart rate during the study. (ii) A significant decrease in diastolic blood pressure was observed after the 36th hour following the first dose of P-GS while a reduction in systolic blood pressure was observed on day 4. (iii) An approximated relative bioavailability (f'P-GS) of 36.5% was calculated. P-GS appears to have a lower bioavailability than P-CT in women of similar gestational age. (iv) Both Cmax and AUC0-->infinity are significantly increased at plateau. Further, terminal half-life is increased with regard to the value determined with P-CT. No accumulation of PRZ was noted at steady-state. (v) P-GS is an example of an oral zero-order absorption product that offers one approach to control and improve the outcome of hypertensive therapy during pregnancy. This treatment could represent an alternative to methyldopa as a first treatment of pregnancy-associated hypertension. (vi) There is a slight transplacental passage of the drug (of the order of 10-20%).

Adrenergic alpha-Antagonists↗
PubMed2003

[Teleteaching in otorhinolaryngology. Part 2: the European database "medicstream"].

Searching the medical literature is mainly characterized by the use of databases. The time for reviewing and printing a paper causes a delay between the first presentation of scientific results in a lecture and the appearance of the appropriate journal publication. Moreover, the possibilities for the integration of multimedia data are limited. Because of the development of new compression algorithms for audiovisual digitization software, the near simultaneous transmission of scientific presentations, both visually and aurally, has been possible since 1999. The section telemedicine of the interdisciplinary study group on image guided surgical navigation from the University of Leipzig has developed "medicstream" as a unique, audiovisual, scientific internetdatabase. It allows the documentation of presentations at congresses and courses, including the discussion,over a freely accessible, widely available homepage, using a home developed streaming technology. All presentations are examined by an authorized editorial committee consisting of representatives with different medical specializations for content before the admission to the data base. A total of 392 presentations from seven scientific meetings can be selected by an integrated search machine and viewed with Windows Media Player or Real Player using a conventional or faster internet connection to the homepage www.medicstream.de. The quality of the audiovisual transmission depends on the receiver-lateral data transmission rate,whereby the minimum variant of 56 kB/s is characterized by good detectability of the contents. In an analysis period of 242 days,we registered 44,199 accesses and 4,488 attendances. The telemedicine data base "medicstream" can optimize quality and extend medical education by live-streaming as well as by archiving scientific presentations as audiovisual data.

Congresses as Topic↗
PubMed2001

Evolution of Mhc class II B genes in Darwin's finches and their closest relatives: birth of a new gene.

The 15 extant species of Darwin's finches on the Galápagos and Cocos Islands are the products of an unfinished adaptive radiation from a founder flock of birds related to the South American species Tiaris obscura. Molecular characterization of their major histocompatibility complex ( Mhc) class II B genes has revealed the existence of several related groups of sequences (presumably encoded in distinct loci) from which one (group 5) stands out because of its low divergence over extended time periods. Analysis of group 5 exon 2 and intron 2 sequences has revealed that the encoding locus apparently arose 2-3 million years ago in the Tiaris group of South and Central American Thraupini. The locus shows no evidence of inactivation, but displays a very low degree of polymorphism, both in terms of number of alleles and genetic distances between alleles. Some of the polymorphism, however, appears to be trans-specific. All the observed intergenic differences can be explained by point mutations and most of the exon 2 changes represent non-synonymous substitutions, although the rate of non-synonymous and synonymous substitutions appears to be the same. The origin of the new locus is explained by the birth-and-death model of Mhc evolution with two important extensions. First, the ancestor of the group 5 genes may have arisen without new gene duplication and second, the birth of the new group may have been brought about by a switch from balancing to directional selection. The ancestor of the group 5 genes may have been a classical class II B allele (one of many) which directional selection fixed in the ancestral population and drove into the category of nonclassical genes.

Animals↗
PubMed2006

Colorado river floods, droughts, and shrimp fishing in the upper gulf of California, Mexico.

Accurate procedures that measure hydrologic variability would have great value for evaluating ecosystem impacts of upstream water use in the Colorado River Basin. Many local extractive income-based stakeholders rely directly or indirectly on ecosystem health and are adversely affected when the river does not flow. This study focuses on the impact of little or no Colorado River flow on the Mexican shrimp industry. Although there have been complaints that U.S. diversions of Colorado River flow have greatly impaired the shrimp fishery, this research demonstrates that freshwater rarely reaches the Gulf even during times of flooding, and that other factors such as overfishing may influence the instability of shrimp populations. Advanced very-high-resolution radiometer (AVHRR) satellite imagery was used to assess water volumes diverted away from the channel of the Colorado River and ultimately the Gulf of California during flooding periods. Analysis of data demonstrated that little freshwater actually reaches the Gulf even during floods because of its diversion into a large dry lake bed basin known as Laguna Salada. Fuller use of the Colorado River throughout its entire course to the sea is possible and could benefit a large cohort of users without catastrophic habitat destruction in delta ecosystems. Reconstruction of a natural earthen berm, as proposed by Ducks Unlimited, would maximize the use of floodwaters for ecosystem benefits. These findings have profound implications for local economic activities dependent on hydrologic resources in the Colorado River Delta and Upper Gulf.

Animals↗
PubMed1999

Double-strand DNA hydrolysis by dilanthanide complexes.

Although there has been progress in developing artificial hydrolytic DNA cleaving agents, none of these has been shown to carry out the double-strand hydrolysis of DNA. We demonstrate that La(III) or Ce(IV) combined with the ligand 1,3-diamino-2-hydroxypropane-N,N,N', N'-tetraacetate (HPTA) in a 2 : 1 ratio can efficiently cleave supercoiled plasmid DNA at 55 degrees C within a 3-h period. Analysis of end-labeled restriction fragments cleaved by these complexes reveals 3'- and 5'-ends consistent with a hydrolytic mechanism. Unlike for other polydentate carboxylate complexes, plasmid DNA cleavage by La(2)(HPTA) or Ce(2)(HPTA) affords a significant amount of linear DNA with a considerable fraction of the supercoiled form still remaining. This result implies that La(2)(HPTA) and Ce(2)(HPTA) can carry out double-strand cleavage of plasmid DNA. La(2)(HPTA) and Ce(2)(HPTA) represent the first metal complexes demonstrated to be capable of double-strand hydrolytic cleavage of plasmid DNA.

DNA↗
PubMed1993

Fine needle aspiration of thyroid nodules in a rural setting.

PURPOSE: The purpose of this study was to evaluate the applicability of fine needle aspiration biopsy (FNAB) of thyroid nodules in rural practices with smaller patient numbers, to assess the effect of these numbers on the results, and to establish the level of accuracy of the procedure in this setting. PATIENTS AND METHODS: We retrieved all thyroid FNAB reports identified as being performed by a single practitioner in a referral endocrine practice in Rapid City, South Dakota, between September 30, 1987, and September 30, 1991. Biopsy results are separated by year to establish correlations with the number of biopsies and outcomes. Follow-up pathology reports were obtained for all patients known to have undergone surgery. RESULTS: A total of 189 FNABs in 165 patients were available for review from a 4-year period. The number of FNABs increased progressively from 28 per year to 65 per year during the 4-year course of the study. The incidence of inadequate specimens decreased inversely from 18% to 6% with the increase in the number of FNABs. The percentage of surgical interventions in which malignancy was found increased from 23% to 50% over the same period. Analysis of the results suggests that accuracy and specificity are comparable to results from larger centers. CONCLUSIONS: FNAB of thyroid nodules can substantially reduce surgical intervention and increase the yield of malignancy without excessive loss of accuracy even in rural areas with small numbers of patients. Improved results as the number of biopsies increased to 50 or more per year suggest benefits from concentrating biopsies with as few operators as practical.

Aftercare↗
PubMed1989

Bioactivation mechanism of L-thiomorpholine-3-carboxylic acid.

L-Thiomorpholine-3-carboxylic acid (L-TMC) is a cyclized analog of S-(2-chloroethyl)-L-cysteine, which is cytotoxic in vitro and nephrotoxic in vivo. To determine whether L-TMC may play a role in S-(2-chloroethyl)-L-cysteine-induced toxicity, the cytotoxicity of L-TMC was studied in isolated rat kidney cells. L-TMC produced time- and concentration-dependent cytotoxicity. Probenecid, an inhibitor of the renal anion transport system, and L-alpha-hydroxyisocaproic acid, a substrate for L-amino acid oxidase, inhibited L-TMC-induced cytotoxicity. Rat kidney cytosol catalyzed the metabolism of L-TMC to a product absorbing at 300 nm. The increase in absorbance at 300 nm was accompanied by an increase in oxygen consumption and was inhibited by L-alpha-hydroxyisocaproic acid; moreover, the absorbance of the metabolite was quenched by addition of potassium cyanide or sodium borohydride, which indicated the formation of an imine. When L-TMC was incubated with rat kidney cytosol and sodium borodeuteride was added at the end of the incubation period, analysis by gas chromatography/mass spectrometry of the tert-butyldimethylsilyl ester of L-TMC showed the formation of [2H]TMC, indicating the intermediate formation of the imine 5,6-dihydro-2H-1,4-thiazine-3-carboxylic acid; chemically synthesized TMC imine showed similar behavior. The enzyme responsible for the metabolism of L-TMC was purified from rat kidney and was identified as L-amino acid oxidase. These observations indicate a role for L-amino acid oxidase in the bioactivation and cytotoxicity of L-TMC.

Amino Acid Oxidoreductases↗