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PubMed1994

Kinetic mechanism and characterization of human beta-galactosidase precursor secreted by permanently transfected Chinese hamster ovary cells.

Chinese hamster ovary cell clones permanently transfected with the cDNA for human lysosomal beta-galactosidase secrete the enzyme precursor into the cell medium, from which it is purified to apparent homogeneity in a single step by affinity chromatography. The purified precursor is fully active, displays the same pH optimum and Km values as the mature placental enzyme, and has an intact C-terminus. The intact enzyme when chromatographed on a Sephacryl S-200 molecular-sieve column elutes as a 105,500 Da monomer, whereas on SDS/PAGE gels the polypeptide migrates as an 88 kDa polypeptide. A time course of digestion with glycopeptide-N-glycanase shows the gradual conversion of the precursor from an 88 to a 72 kDa protein, suggesting the presence of five N-linked oligosaccharides in the protein. The precursor is readily taken up in a mannose-6-phosphate-dependent manner into beta-galactosidase-deficient, GM1-gangliosidosis fibroblasts, and the enzyme activity is returned to normal levels. We show that the stereochemical course of enzymic hydrolysis involves the retention of the beta-configuration at the anomeric centre, suggesting a double-displacement mechanism. Furthermore, the enzyme is rapidly and irreversibly inactivated in the presence of the mechanism-based inactivator 2,4-dinitrophenyl-2-deoxy-2-fluoro-beta-D-galactopyranoside, which implicates a covalent intermediate. The enzyme is also inactivated by 1-ethyl-3(3-dimethylamino-propyl)carbodi-imide and by phenylglyoxal, which implicates carboxylate and arginine residues respectively in the active site. We conclude that the beta-galactosidase precursor is functionally identical to the mature lysosomal form of the enzyme and serves as an excellent enzyme source for investigation of structure-function relationships in the protein.

Animals↗
PubMed1994

Laminin mediates the restitution of rat gastric mucosa in vitro.

Restitution, the rapid re-establishment of mucosal integrity following damage, involves cell migration and can be monitored by measuring transmucosal potential difference of tissue mounted in an Ussing chamber. The involvement of extracellular matrix proteins and matrix receptors was examined in the restitution of rat gastric mucosa. Undamaged mucosa maintained a potential difference of -32.7 +/- 2.2 mV for several hours. Mucosal exposure to 0.6 M NaCl for 1 min reduced this to -3.3 +/- 1.4 mV in 2-3 min. Thereafter, the potential difference returned in 60 min to plateau at -28.9 +/- 1.3 mV (88.5 +/- 3.6% of pre-exposure). Tissues mucosally treated with 1:100 anti-laminin antiserum maximally recovered following damage to 65.6 +/- 6.6% of pre-exposure potential difference (PD), while those treated with 1:100 anti-collagen IV or anti-fibronectin antisera recovered to 88.8 +/- 9.7% and 86.3 +/- 3.2%, respectively. Only the anti-laminin result was significantly different from controls. The anti-laminin effect was abolished by pre-incubation of the anti-laminin antiserum with purified rat laminin, suggesting that the effect was laminin specific. In experiments involving matrix protein receptors, tissues treated with alpha-lactalbumin, a protein altering the substrate specificity of cell surface laminin receptor/enzyme beta-1,4-galactosyltransferase, maximally recovered following damage to only 49.3 +/- 7.7% of pre-exposure PD, which was significantly different from controls, while those treated with anti-beta 1 integrin recovered to 85.0 +/- 9.7%. Our data suggest that laminin is involved in mediation of gastric mucosal restitution, possibly via beta-1,4-galactosyltransferase.

Animals↗
PubMedDate not supplied

Evaluation of the molluscicidal properties of Euphorbia splendens var. hislopii (N.E.B.) latex: experimental test in an endemic area in the State of Minas Gerais, Brazil.

Following the positive results obtained regarding the molluscicidal properties of the latex of Euphorbia splendens that were corroborated in laboratory and field tests under restricted conditions, a field study was conducted in experimental streams located in an endemic area. After recording the average annual fluctuations of vectors in three streams, a solution of E. splendens latex at 12 ppm was applied in stream A, a solution of niclosamide at 3 ppm that was applied in stream B and a third stream (C) remained untreated for negative control. Applications of E. splendens and niclosamide resulted in a mortality of 100% among the snails collected in the streams A and B. No dead snails were found in the negative control stream. A monthly follow-up survey conducted during three consecutive months confirmed the return of vectors to both experimental streams treated with latex and niclosamide. This fact has called for a need to repeat application in order to reach the snails that remained buried in the mud substrate or escaped to the water edge, as well as, newly hatched snails that did not respond to the concentration of these molluscicides. Adults snails collected a month following treatment led us to believe that they had migrate from untreated areas of the streams to those previously treated.

Animals↗
PubMed1983

Synthesis of complement by macrophages and modulation of their functions through complement activation.

During the last decade considerable progress has been made to characterize intimate functional links between macrophages, a major cellular component of immunoinflammatory responses, and the complement system representing the major humoral mediator of inflammation. Macrophages of various species and tissue sites have been shown to synthesize and release most of the complement components providing these cells with their own "pericellular" complement system. Circumstantial evidence for the assembly of both classical and alternative pathway convertases has been adduced. An intricate network of feedback loops involving endogenous and extrinsic factors operates to adjust complement production to acute requirements, for example augmenting production in the face of accelerated turnover at sites of inflammation, and returning it to baseline levels once the inflammatory stimulus has subsided, in order to maintain a fine-tuned balance. The molecular mechanisms underlying regulation of complement synthesis by macrophages are beginning to be elucidated by use of gene technology. On the other hand, complement activation products exert a number of effects on macrophages via specific surface receptors causing internalization of offending agents, microbes, and immune complexes, promotion of intracellular killing, controlling migration behavior, inducing release of potent biologic substances such as lysosomal enzymes, arachidonic acid metabolites, and interleukin 1. In these interactions, two important humoral mediator systems of inflammation, the complement system and the arachidonic acid cascade, are functionally linked at the level of the macrophage. Stimulation of the release of immunomodulating compounds from macrophages invoke a role for complement in immune regulation. This multifaceted interplay is of particular importance considering the mobility of macrophages that allows them to gain almost unrestricted access to sites of ongoing immunoinflammatory responses. The time seems to have come to abandon the petrified thinking in socalled systems as, for instance, humoral versus cellular, specific versus unspecific, and to proceed to interlocking functions guided by physiology proper.

Anaphylatoxins↗
PubMed1996

Radiological intervention in Budd-Chiari syndrome: techniques and outcome in 18 patients.

We reviewed our experience of the therapeutic role of radiology in Budd-Chiari syndrome. Patients with stenosis and/or occlusion of the main hepatic veins and/or inferior vena cava (IVC) are suitable for radiological intervention (35% in our series). Eighteen patients (mean age 37.4 years) have undergone radiological intervention over the past 8 years. The site of obstruction was the hepatic veins in 12/18 patients while 6/18 patients had both hepatic vein and IVC obstruction, which in two was due to tumour thrombus. One patient had repeated dilatations of a mesocaval shunt; 49 angiographic venous dilatations were performed (18 during initial intervention, 31 on review) including 10 recanalizations of occlusions. A combined transhepatic-transjugular approach was used for 10/49 procedures. Thrombolysis was performed in 5/18 and stent insertion in 6/18 patients. Three serious complications occurred (IVC stent migration, hepatic artery pseudoaneurysm, myocardial puncture). Follow-up, after initial intervention, has continued for a mean of 24.2 months (range 4 days-92 months). Symptoms related to hepatic venous outflow obstruction were fully relieved in 10/18 (56%) patients and partially relieved in 4/18 (22%) patients. Close monitoring (and re-intervention) during the early post-intervention period is needed because 28% of initial venous dilatations failed to provide adequate venous return in the first instance. Once the patient is stabilized regular review is mandatory as HV restenosis is common after 10 months or more follow-up. The efficacy and safety of radiological intervention make it the preferred first line of treatment in selected patients with Budd-Chiari syndrome.

Adult↗
PubMed1985

[Respiratory depression after intrathecal injection of morphine: value of in situ naloxone].

A case of delayed respiratory depression following an intrathecal injection of hyperbaric morphine hydrochloride is reported. This injection was made during a lumbar myelography in a 60 year old patient suffering from metastatic epiduritis unrelieved by oral or parenteral drugs. The differences in densities between the CSF, hyperbaric opiate solution and contrast medium explain the migration of the morphine hydrochloride from the lumbar thecal space to the basal cisternae, giving a fall in the responsiveness to CO2 of the brain stem respiratory centres. Parenteral naloxone did not reverse this ventilatory depression. Only the myosis and the analgesia disappeared. After 16 h of various attempts of reversal by parenteral injections, an intrathecal injection of naloxone was tried. This small dose (0.1 mg), given intrathecally, resulted in a prompt return to normal of respiratory function.

Anesthesia, Spinal↗
PubMed1999

Effect of oxidant stress on growth factor stimulation of proliferation in cultured human proximal tubule cells.

Restoring kidney function after injury involves cell migration and proliferation, processes that are yet to be precisely defined. Because epidermal growth factor (EGF) and insulin-like growth factor-1 (IGF-1) promote recovery from acute renal failure, we used SV-40 immortalized human proximal tubule cells to examine the effects of these growth factors on cell proliferation after peroxide injury (1.5 mM for 1 hour). ATP levels decreased to approximately 15% of control values immediately after injury but returned to nearly normal levels after 4 hours of recovery. Under control conditions, both EGF and IGF-1 stimulated proliferation and their effects were additive. However, 20-24 hours after injury, while IGF-1 stimulated proliferation, EGF was no longer effective nor was the combination of EGF and IGF-1. Although the EGF receptor was decreased 20 hours after injury, the lack of IGF-1 effect could not be explained by loss of the IGF-1 receptor, which remained unchanged after peroxide injury. Thus, the mechanism responsible for the blunting of the IGF-1 effect on proliferation following injury remains speculative. However, we conclude that the effects of growth factors under control conditions may not predict their effects after injury.

Cell Division↗
PubMed2003

The levonorgestrel intrauterine system: a clinical perspective from the UK.

The main contraceptive effects of this valuable product [the levonorgestrel intrauterine system (LNG-IUS)] are by endometrial suppression and changes to the cervical mucus and uterotubal fluid that impair sperm migration. The blood levels of LNG are very low, so progestogenic symptoms are uncommon. Most women still ovulate and in the remainder sufficient estrogen for health is produced from the ovary, even if they become amenorrhoeic, as many do; this is primarily a local end-organ effect and should be seen as a benefit. Although usable by selected nulliparae, it is ideal for the parous woman. It has unsurpassed efficacy, and return of fertility is rapid. Combining the best features of hormonal and intrauterine contraception, its gynecological benefits are impressive: the LNG-IUS user can expect a dramatic reduction in the amount and, after the first few occasionally troublesome months, in the duration of blood loss. Hemoglobin levels rise and dysmenorrhea is usually greatly benefited, unlike with current uterine ablation techniques. In perimenopausal women, it can protect the endometrium from overstimulation when estrogen replacement therapy (ERT) is added, by any chosen route. It thus provides a contraceptive modality of ERT with, usually, no bleeding and few progestogenic side effects-and is applicable before final ovarian failure. In summary, adverse side effects are few and in general they are not in the "hazardous" category. Regarding the admitted inconvenience of the first weeks of light postinsertion bleeding and the early phase low incidence of steroidal side effects: good counseling is paramount, since forewarned is forearmed!

Adult↗
PubMed1992

[Hippocratic concept of hysteria].

The Greek physicians of the fourth century B.C. painstakingly described a number of symptoms that they thought were caused by migrations of a restless uterus, said "wandering womb". According to this concept, we can use the term "hysteria", despite the fact that the noun itself never appears in any of the Hippocratic texts. We can determine its origin as being in ancient Egypt from the medical writings of the Egyptian papyri. In the same way, the therapy is mainly of Egyptian origin, using a combination of recipes to make the moving womb return to its proper place in the body cavity. However, we can also identify the rationality of the Greeks, in particular as regards mechanical physiopathology. Hippocratic authors are closely connected with presocratical physics, and manifest a distinct break with magic and religion. Furthermore, they claim that hysteria may result from prolonged sexual continence, an opinion which was to influence medical history for over two thousand years.

Egypt, Ancient↗
PubMed1978

[Social psychiatry of migrant workers (author's transl)].

A review of literature about psychic illness in migrant workers (with special reference to the situation in Europe) is presented, including the problems of incidence and prevalence, course of the illness, typical syndromes and treatment. Results concerning incidence and prevalence of psychic disease in migrant workers are contradictory and partly--for methodological reasons--of questionable quality. It cannot be take for granted, that migrant workers suffer more often from psychiatric disturbances than either of the two possible control groups: the populations of the emigration or immigration countries respectively. There are two high risk periods for migrants: shortly after the migration and after a longer period in the guest country. Differences between the migrant's culture and that of the immigration context (language, mythical beliefs, illness behavior) influence the manifestations of psychiatric syndromes. The following syndromes are typical for migrant workers: paranoid reactions, hypochondric-depressive syndromes, psychosomatic conditions and sexual neurosis. Special attention requests the treatment of migrant workers with psychiatric problems; the aspects of psychotherapy, accompanying social measures and the return as therapeutic measure are discussed. In the second part, a general frame of reference for the sociological analysis of the problem of migrant workers is presented. Reasons for the mass immigration of foreign workers to the industrialized countries of central Europe were the demand of labor force and the large gap in socio-economic development between the countries. In the immigration context, the foreign workers find themselves in the lowest social strata and numerous problems accumulate there. Empirical evidence for different sociological explanations of mental illnes of migrant workers ist presented: hypotheses of social selection vs. social causation (low socio-economic status, goal-striving-stress, culture-shock theory, theory of culture change and isolation hypothesis).

Adjustment Disorders↗
PubMed1997

Open architecture for health care systems: the European RICHE experience.

Groupe RICHE is bringing to the market of health IT the Open Systems approach allowing a new generation of health information systems to arise with benefit for patients, health care professionals, hospital managers, agencies and citizens. Groupe RICHE is a forum for exchanging information, expertise around open systems in health care. It is open to any organisation interested by open systems in health care and wanting to participate and influence the work done by its user, marketing and technical committees. The Technical Committee is in charge of the maintenance of the architecture and impact the results of industrial experiences on new releases. Any Groupe RICHE member is entitled to participate to this process. This unique approach in Europe allows health care professionals to benefit from applications supporting their business processes, including providing a cooperative working environment, a shared electronic record, in an integrated system where the information is entered only once, customised according to the user needs and available to the administrative applications. This allows Hospital managers to satisfy their health care professionals, to smoothly migrate from their existing environment (protecting their investment), to choose products in a competitive environment, being able to mix and match system components and services from different suppliers, being free to change suppliers without having to replace their existing system (minimising risk), in line with national and regional strategies. For suppliers, this means being able to commercialise products well fitted to their field of competence in a large market, reducing investments and increasing returns. The RICHE approach also allows agencies to define a strategy, allowing to create a supporting infrastructure, organising the market leaving enough freedom to health care organisations and suppliers. Such an approach is based on the definition of an open standard architecture. The RICHE esprit project defined in 1993 the three layered architecture, with four main components and their services of which the main principles have recently been adopted by the CEN TC251 as a european pre-standard. From this architecture specifications various implementations have been completed including the IMS DHE, the GESI DHE and the REFERENCE Kernel. However putting into practice this approach on a large scale is not so easy. Interesting lessons have been learned in the last years in different countries.

Computer Communication Networks↗
PubMed2001

Evolution of chinook salmon (Oncorhynchus tshawytscha) populations in New Zealand: pattern, rate, and process.

Chinook salmon, Oncorhynchus tshawytscha, from the Sacramento River, California, USA were introduced to New Zealand between 1901 and 1907, and colonized most of their present-day range within about 10 years. The New Zealand populations now vary in phenotypic traits typically used to differentiate salmon populations within their natural range: growth in freshwater and at sea, age at maturity, dates of return to fresh water and reproduction, morphology, and reproductive allocation. This paper reviews a large research program designed to determine the relative contributions of phenotypic plasticity and genetic adaptation to this variation, in an effort to understand the processes underlying the natural evolution of new populations. We found strong evidence of trait divergence between populations within at most 30 generations, particularly in freshwater growth rate, date of return, and reproductive output, with plausible adaptive bases for these differences. Importantly, we also demonstrated not only a genetic basis for post-release survival but higher survival, and hence fitness, of a population released from its established site compared to another population released from the same site. We conclude that divergence of salmon in different rivers probably resulted initially from phenotypic plasticity (e.g., habitat-specific growth rates, and effects of upriver migration on ovarian investment). Philopatry (homing to natal streams) combined with rapid evolution of distinct breeding periods to restrict gene flow, facilitating divergence in other traits. We also suggest that in addition to genetic divergence resulting from random founder effects, divergence may also arise during the very early stages of colonization when the original colonists are a non-random, pre-adapted subset of the source population. This 'favored founders effect' immediately improves the fitness of the new population. Overall, this research reveals the complex interplay of environmental and genetic controls over behavior, physiology and life history that characterize the early stages of population differentiation, a process that has taken place repeatedly during the history of salmon populations.

Adaptation, Biological↗
PubMed1979

Nuclear translocation of the cytoplasmic glucocorticoid receptor in the iris--ciliary body of the rabbit.

The cytoplasmic glucocorticoid receptor of the iris--ciliary body of the rabbit has been shown to translocate to the cell nucleus within 30 min of an injection of cortisol. Over the next 2 1/2 hr the amount of receptor returns to the control value. The threshold of the loss of receptor from the cytosol was found at 0.04 mg of cortisol per kilogram body weight, with a maximal loss being reached at a cortisol dose of 0.5 mg/kg B.W. The inactive glucocorticoid tetrahydrocortisol and the major sex steroids, dihydrotestosterone, estradiol, and progesterone, had little or no effect on this translocation, indicating the specificity of the cortisol effect. Thus this receptor appears to migrate to the cell nucleus in a manner similar to that found in other steroid-sensitive tissues and is consistent with the accepted mechanism whereby these hormones regulate differential gene expression in the nucleus.

Animals↗
PubMed2003

Macrophage migration inhibitory factor is a cardiac-derived myocardial depressant factor.

Macrophage migration inhibitory factor (MIF) is a pluripotent proinflammatory cytokine that is ubiquitously expressed in organs, including the heart. However, no specific role for MIF in modulating cardiac performance has yet been described. Therefore, we examined cardiac MIF expression in mice after LPS challenge (4 mg/kg) and tested the hypothesis that MIF is a mediator of LPS-induced cardiac dysfunction. Western blots of whole heart lysates, as well as immunohistochemistry, documented constitutive MIF protein expression in the heart. Cardiac MIF protein levels significantly decreased after LPS challenge, reaching a nadir at 12 h, and then returned to baseline by 24 h. This pattern was consistent with MIF release from cytoplasmic stores after endotoxin challenge. After release of protein, MIF mRNA levels increased 24-48 h postchallenge. To determine the functional consequences of MIF release, we treated LPS-challenged mice with anti-MIF neutralizing antibodies or isotype control antibodies. Anti-MIF-treated animals had significantly improved cardiac function, as evidenced by a significant improvement in left ventricular (LV) fractional shortening percentage at 8, 12, 24, and 48 h after endotoxin challenge. In support of these findings, perfusion of isolated beating mouse hearts (Langendorff preparation) with recombinant MIF (20 ng/ml) led to a significant decrease in both systolic and diastolic performance [LV pressure (LVP), positive and negative first derivative of LVP with respect to time, and rate of LVP rise at developed pressure of 40 mmHg]. This study demonstrates that MIF mediates LPS-induced cardiac dysfunction and suggests that MIF should be considered a pharmacological target for the treatment of cardiac dysfunction in sepsis and potentially other cardiac diseases.

Animals↗
PubMed1998

[Cementless hip prosthesis in patients with rheumatoid arthritis].

From 1986 to 1996, we implanted a total of 92 hip arthroplasties (86 cementless, 4 hybrid and 2 cemented) in 65 patients with rheumatoid arthritis. Of the 89 uncemented cups, 59 were threaded cups (Hofer-Imhof n = 45, Zweymüller n = 7, Mecring n = 5, PM n = 2) and 30 were hemispherical cups of the Harris Galante type I and II. 87 stems were implanted without cement (Zweymüller SL n = 58, Uni n = 16, Schenker n = 9, Zweymüller I n = 4) and 5 with cement. One patient died postoperatively and three (4 implants) within the first year. To date, one cup of each threaded type had to be revised because of loosening (revision rate approx. 6.8%); Up to now, three of 87 (approx. 3.4%) stem revisions (1 x Zweymüller I, 1 x Schenker, 1 x Zweymüller SL) have been undertaken. Ten patients with twelve hip arthroplasties did not return for follow-up; some of them had a poor general health status. The clinical and radiological results of the arthroplasties of 52 patients showed a Harris Hip Score averaging 72 after an average of 54 months (min. 12-max. 132). Ten patients had minor complaints in the hip region. 79% of the uncemented implants (70 out of 89 cups, 69 out of 87 stems) were assessed radiologically. Two threaded cups showed slight migration after cancellous bone grafting in the presence of acetabular protrusion that was present in a total of 13 hip joints. This subsided markedly after filling with cancellous bone and recentering of the hip joint. Homogeneous incorporation of the bone grafting und thus remodelling of the medial wall was achieved, with the bone graft exhibiting marked reduction. At final follow-up, approx. 75% of the cementless cups had complete bone ingrowth without any evidence of radiolucency (type I), approx. 19% had near-complete bone ingrowth with minimal radiolucencies in one zone or in a maximum of 50% of the bone contact area (type III) and approx. 6% had radiolucencies in more than 50% of the bone contact area (type II). The radiographic evaluation of the most frequently used stem (Zweymüller SL) showed approx. 47% with only slight remodelling of the calcar (type I), approx. 33% with moderate loss of femoral density (type II) and approx. 20% with severe bone loss and thinning of cortical bone (type III).

Arthritis, Rheumatoid↗
PubMed2005

[Invasive schistosomiases].

Schistosomiasis is a tropical helminthic infection, observed in travelers as well as local populations. It is most often due to Schistosoma mansoni or Schistosoma haematobium and can be diagnosed at the invasive phase. Migration of the schistosomulae (larvae) in the body leads to acute parasitic toxemia, which includes a hypersensitivity reaction and circulating immune complexes. The invasive stage occurs generally 2 to 6 weeks after the exposure and combines fever, asthenia, faintness and headaches. Other signs include diarrhea, dry cough, dyspnea, urticarial rash, arthralgia, myalgia, and enlargement of liver and spleen. Although rare, neurological and cardiac complications may be fatal. This diagnosis should be considered in travelers returning from the tropics with compatible clinical signs and delayed hypereosinophilia, if they report exposure in an endemic area. It is later confirmed by seroconversion for schistosomiasis and then by observation of schistosome eggs in stool or urine (according to species). The standard treatment of acute schistosomiasis with praziquantel is ineffective and can aggravate clinical outcome during this phase. Corticosteroid treatment is recommended for serious forms with neurological or cardiac manifestations.

Acute Disease↗
PubMed1984

The adrenal paraneurone: tubulin organization.

When chromaffin cells from the bovine adrenal medulla are maintained in culture, they develop neuritelike processes which end with growth-cone-like structures. Chromaffin granules were found to migrate from the cell body to the neurite endings. Thus, the intracellular transport of secretory granules, existing in vivo, seems to occur in an exaggerated way in the cultured cells. These cells offer an excellent model for studying the mechanism of transport, particularly the role of microtubules. By immunofluorescent staining, we observed that tubulin antibodies decorate a complex network visible along the neurites. Colchicine treatment induced the disappearance of this network followed by a return of granules in the cell body and a retraction of neurites. To test the presence of tubulin in the chromaffin granule membrane, we used two-dimensional gel electrophoresis and a radioimmunoassay. Our results indicate that tubulin is not a significant component of chromaffin granules. However, binding experiments show that granule membranes are able to bind tubulin through high affinity binding sites. These results show that microtubules appear involved in neurite formation and probably in granule transport. Tubulin is not an integral constituent of the granule membrane, but is present as a result of a reversible specific binding. This insertion of tubulin into the membrane might represent a step in the association between microtubules and secretory granules.

Adrenal Medulla↗