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Effect of estrogen treatment on the peroxidase activity and estrogen receptors in the female rabbit urogenital tissues.

The effect of one, 4 and 8 weeks of continuous estrogenization of rabbit on peroxidase (PO) activity and on both cytoplasmic and nuclear estrogen receptors was studied in the uterus, vagina, urethra and urinary bladder. Whereas the peroxidase activity in the urogenital tissue of untreated controls was near zero, after one week of estrogen treatment it increased very substantially in the uterus and vagina and much less dramatically in the urethra or urinary bladder. With continuation of estrogen treatment for 4 or 8 weeks the PO decreased by 80-90% in the uterus and vagina and by only 40% in the urethra. After one week of estrogen treatment the density of both cytosolic and nuclear estrogen receptors decreased by several fold in both the uterus and vagina, whereas it decreased by 30-50% in the urethra and bladder. The concentration of both cytosolic and nuclear receptors decreased further although less dramatically with continuing estrogen treatment, up to 8 weeks, in all tissues. These data suggest that although the general pattern of responses to estrogen showing an initial increase in PO followed by a reduction with continuing estrogen treatment is the same in all urogenital tissues, the responses seem to have a prolonged time scale in the case of lower urinary tract tissues. The quantitative aspect of the response generally corresponds with the density of estrogen receptors in the urogenital tissues.

Animals↗

Antibody-mediated immunotoxicity in American kestrels (Falco sparverius) exposed to polychlorinated biphenyls.

Antibody-mediated immune function in adult and recently fledged (30 to 33 d old) American kestrels (Falco sparverius) was examined in birds exposed directly, or only in ovo, to polychlorinated biphenyls (PCBs). In 1998, 9 mature male and 9 female kestrels were fed PCBs, whereas 9 females and 10 males served as controls. A mixture of Aroclors 1248:1254:1260 suspended in safflower oil was injected into the kestrels' food items, while in control diets only the same volume of oil was added. The dosage of PCBs was approximately 7 mg/kg kestrel/d, beginning in March 1998 and continuing for 120 d. In 1998, the antibody-mediated immune response was stimulated by immunization and booster vaccinations of the kestrels using a nonpathogenic antigen, dinitrophenol-keyhole limpet hemocyanin (DNP-KLH). In 1999, offspring from three treatment groups based upon maternal exposure to PCBs were similarly tested for their antibody response. None of these mothers was vaccinated with DNP-KLH the previous year. The maternal groups were: (1) exposed to PCBs in 1998 for 120 d, (2) exposed in ovo in 1998 (i.e., mothers were produced by PCB-exposed parents), or (3) unexposed to PCBs. Serum antibody levels were determined using an enzyme-linked immunosorbent assay (ELISA). In 1998, PCB-exposed adult females had a significantly higher antibody response than did controls, whereas adult males exposed to PCBs had significantly suppressed antibody production. For the nestlings produced in 1999, maternal treatment significantly affected antibody response. Generally, the antibody response in the nestlings was much lower than that seen in adult kestrels. Yet both male and female offspring from mothers that had been fed PCBs the previous year had significantly higher postbooster anti-DNP-KLH titers than control and in ovo-exposed maternal groups, thus mimicking the response seen in the adult females the previous year. These sex-specific responses in PCB-exposed birds provide further evidence of the endocrine-disrupting behavior of PCBs. Both suppression and stimulation of the antibody response are undesirable because this indicates that the immune system is not able to respond normally to challenges by infectious or other disease-causing agents.

Animals↗

Fluctuation-response relation in turbulent systems.

We address the problem of measuring time properties of response functions (Green functions) in Gaussian models (Orszag-McLaughin) and strongly non-Gaussian models (shell models for turbulence). We introduce the concept of halving-time statistics to have a statistically stable tool to quantify the time decay of response functions and generalized response functions of high order. We show numerically that in shell models for three-dimensional turbulence response functions are inertial range quantities. This is a strong indication that the invariant measure describing the shell-velocity fluctuations is characterized by short range interactions between neighboring shells.

Journal Article↗

Effect of preexisting immunity to Salmonella on the immune response to recombinant Salmonella enterica serovar typhimurium expressing a Porphyromonas gingivalis hemagglutinin.

Recombinant Salmonella strains expressing foreign heterologous genes have been extensively studied as live oral vaccine delivery vectors. We have investigated the mucosal and systemic immune responses following oral immunization with a recombinant Salmonella enterica serovar Typhimurium expressing the hemagglutinin HagB from Porphyromonas gingivalis, a suspected etiological agent of adult periodontal disease. We have previously shown a primary mucosal and systemic response following oral immunization with chi4072/pDMD1 and recall responses following boosting at 14 weeks after primary immunization. In this study, we examined the effects of earlier boosting as well as the effects of deliberately induced immunity to the Salmonella carrier strain on subsequent immune responses. Mice boosted at week 7 following immunization, a point which corresponded to the peak of the primary response, generally showed lower responses than those boosted at week 14. When mice were preimmunized with the Salmonella carrier alone and then immunized with the recombinant strain 7 or 14 weeks later, significant reductions were seen for serum immunoglobulin G (IgG) antibodies at week 14 and for salivary IgA at week 7. No reductions were seen in serum IgA or vaginal wash IgA antibodies. Mice appear to be refractory to boosting with orally administered salmonellae at 7 weeks. Deliberate immunization with the carrier strain did not appreciably affect recall responses at 14 weeks, with the exception of the serum IgG responses, nor did it affect colonization of the Peyer's patches.

Adhesins, Bacterial↗

Genetic evidence that the alpha5 helix of the receiver domain of PhoB is involved in interdomain interactions.

Two-component signaling proteins are involved in transducing environmental stimuli into intracellular signals. Information is transmitted through a phosphorylation cascade that consists of a histidine protein kinase and a response regulator protein. Generally, response regulators are made up of a receiver domain and an output domain. Phosphorylation of the receiver domain modulates the activity of the output domain. The mechanisms by which receiver domains control the activities of their respective output domains are unknown. To address this question for the PhoB protein from Escherichia coli, we have employed two separate genetic approaches, deletion analysis and domain swapping. In-frame deletions were generated within the phoB gene, and the phenotypes of the mutants were analyzed. The output domain, by itself, retained significant ability to activate transcription of the phoA gene. However, another deletion mutant that contained the C-terminal alpha-helix of the receiver domain (alpha5) in addition to the entire output domain was unable to activate transcription of phoA. This result suggests that the alpha5 helix of the receiver domain interacts with and inhibits the output domain. We also constructed two chimeric proteins that join various parts of the chemotaxis response regulator, CheY, to PhoB. A chimera that joins the N-terminal approximately 85% of CheY's receiver domain to the beta5-alpha5 loop of PhoB's receiver domain displayed phosphorylation-dependent activity. The results from both sets of experiments suggest that the regulation of PhoB involves the phosphorylation-mediated modulation of inhibitory contacts between the alpha5 helix of its unphosphorylated receiver domain and its output domain.

Alkaline Phosphatase↗

Lymphoid cell blastogenesis as an in vitro indicator of cellular immunity to Legionella pneumophila antigens.

The lymphocyte blastogenic transformation assay was adapted to study responsiveness of lymphoid cells from animals and humans to Legionella pneumophila antigens in vitro. Spleen cells from guinea pigs after active immunization with Legionella vaccine, but not from normal animals, responded by blast cell transformation when stimulated in vitro with killed Legionella whole-cell vaccine, sonic extracts thereof, or a purified somatic antigen. The response was dose dependent. Similar lymphocyte blastogenesis occurred with spleen cells from mice sensitized to Legionella by sublethal infection with the bacteria. In addition, blastogenesis occurred with peripheral blood leukocytes from human volunteers tested in vitro with whole-cell vaccine, sonic extracts, or purified somatic antigen. Maximum responsiveness generally occurred 4 to 5 days after stimulation of human peripheral blood leukocytes, but a day or two earlier with spleen cells from normal or sensitized mice. Guinea pig spleen cells generally showed peak responses at the same time as human peripheral blood leukocytes after stimulation in vitro. Blastogenic responses with purified antigen were comparable to those with the whole-cell vaccine or sonic extract. Such antigens from Legionella provide a useful material for inducing responses in vitro as a correlate of cellular immunity to these bacteria.

Animals↗

[The practice guideline 'Acute cough' from the Dutch College of General Practitioners; a response from the perspective of general practice].

The practice guideline 'Acute cough' from the Dutch College of General Practitioners stresses the fact that a cough of less than 3 weeks' duration seldom heralds serious pathology. However, for sound reassurance of patients presenting with a cough of short duration, the general practitioner needs to know much about the signs and symptoms connected to low-prevalence serious pathology in these patients. The practice guideline distinguishes upper and lower respiratory tract infections and defines serious lower respiratory tract infection. The diagnostic value of symptoms and laboratory findings like a sedimentation rate or C-reactive protein in order to make such distinctions, is not explained in detail. Antibiotics are reserved for serious lower respiratory tract infection with the exception of acute bronchitis, croup and bronchiolitis, which can be treated without antibiotics. Recommendations for treatment of acute bronchiolitis with bronchodilators or corticosteroids, and croup with corticosteroids are based on consensus. This practice guideline can be considered as a clear and valuable piece of work for all physicians in primary and secondary care.

Acute Disease↗

Mediators of inflammation and acute phase response in the liver.

The acute phase response is a generalized response of the organism to multiple disturbances of its physiological homeostasis. It consists of local and systemic reactions. Inflammatory processes are the main causes for the initiation of these defence mechanisms. Responsible mediators for the acute phase response are predominantly cytokines, whereby the liver is the predominant target organ. Changes in hepatocyte gene expression profiles result in dramatic changes in serum concentrations of specific plasma proteins, called acute phase proteins. IL-6 was identified as the principal mediator of this reaction. Via its cellular signal transducer gp130 IL-6 induces DNA-binding of STAT transcription factors on regulatory elements of target genes. While IL-6 dependent processes are mainly conferred to be protective other inflammatory cytokines are attributed to be cytotoxic for the liver. TNF-alpha was shown to be involved in several models of liver failure as a mediator for both cytotoxicity and cell proliferation. TNF-alpha leads via caspases to the onset of apoptosis, the so-called programmed cell death. On the other hand it activates NF-kappaB thereby triggering inflammatory processes. In this review we display the relevance for intracellular actions of both cytokines in several models of liver injury. Especially we refer to the T-cell mediated Concanavalin A induced liver failure and to liver regeneration induced by CCL4 and partial hepatectomy. Both cytokines contribute in concert to a cellular balance during these pathophysiological conditions.

Acute-Phase Reaction↗

[The practice guideline 'Anemia' from the Dutch College of General Practitioners; a response from the perspective of general practice medicine].

The practice guideline 'Anaemia' from the Dutch College of General Practitioners will certainly be a support for the Dutch general practitioner. The inclusion of an algorithm to make a more precise diagnosis is an experiment that needs to be evaluated in the near future. However, many general practitioners will regard it as too complex for use in daily practice and specialists will find it to be of limited use, as it does not cover all cases. Consultation between the general practitioner and the specialist will give the best answer in complicated cases. Patients who complain about tiredness or dizziness will expect their general practitioner to take a blood sample for a haemoglobin test. The general practitioner will consider the risk of false-positive test results in interpreting the patient's haemoglobin level. A few concrete remarks: the guideline does not mention that vegetarianism and a low meat intake can increase the risk of vitamin B12 deficiency, and iron suppletion is advised in premenopausal women with profuse vaginal blood loss, whereas there are several treatable disorders that may cause menorrhagia.

Algorithms↗

[The practice guideline 'Pregnancy and puerperium' (first revision) from the Dutch College of General Practitioners; a response from the perspective of general practice medicine].

The first revision of the Dutch College of General Practitioners' practice guideline about pregnancy and puerperium does not significantly differ from the first edition. The guideline is extensive, is well-worth reading and supports daily practice. There is a greater emphasis on the importance of cooperation and differentiation in primary care (midwifes and general practitioners). During the last decade many general practitioners stopped doing home deliveries and have therefore lost their experience in obstetric care and pathology. The guideline describes the general practitioner's tasks as a preconception counsellor, a professional expert on illnesses during pregnancy and after the delivery, and as the doctor of the newborn baby. It will hopefully stimulate a revived interest of and involvement in pregnancy and post-partum care among general practitioners.

Family Practice↗

[The practice guideline 'Rheumatoid arthritis' (first revision) from the Dutch College of General Practitioners: a response from the perspective of general practice].

In the revised guideline on rheumatoid arthritis of the Dutch College of General Practitioners, in contrast to the previous guideline, particular emphasis is given to an early diagnosis. Moreover, rapid and maximal suppression of the disease process is recommended to delay or prevent damage to the joints. This policy however does not take into account the lack of evidence with regard to improvement of prognostic disability parameters. A careful, individualized referral indication is necessary so as to reduce the chance that patients are referred and treated but later turn out not to have had rheumatoid arthritis.

Arthritis, Rheumatoid↗

[The practice guideline 'Hypertension' (third revision) from the Dutch College of General Practitioners; a response from the perspective of general practice].

In the revised practice guideline on hypertension from the Dutch College of General Practitioners, some changes have been made in the areas of diagnosis and therapy in comparison to the previous edition. Finding people with hypertension is a major goal for the prevention of cardiovascular disease. A systolic blood pressure > 140 mmHg (> 160 mmHg in patients > 60 years) necessitates non-pharmaceutical advice and antihypertensive therapy with diuretics, beta-blockers, angiotensin-converting-enzyme (ACE) inhibitors or calcium antagonists, either as monotherapy or in combination. In view of the ever-increasing importance of ACE inhibitors in antihypertensive therapy, we expect that the next revision of the practice guideline will soon be necessary.

Age Factors↗

[The practice guideline 'Hormonal contraception' (second revision) from the Dutch College of General Practitioners; a response from the perspective of general practice].

The second revision of the Dutch College of General Practitioners' practice guideline on hormonal contraception discusses the various methods of hormonal birth control and can help the general practitioner to inform the patient when choosing the most desirable method. A thorough anamnesis is necessary with regard to the increased risks for breast cancer, uterine cancer and cardiovascular diseases in women using hormonal contraception, especially in those who smoke. The guideline also discusses non-hormonal methods briefly.

Breast Neoplasms↗

[The practice guideline 'Atrial fibrillation' from the Dutch College of General Practitioners; a response from the perspective of general practice].

The practice guideline 'Atrial fibrillation' (AF) from the Dutch College of General Practitioners is a clearly written survey on the diagnosis and treatment of AF in general practice. Rapid cardioversion is no longer an indication for acute referral in AF. As AF, heart failure and COPD often occur simultaneously among elderly people, the exact cause of the symptoms can be unclear. In these complicated cases, with the risk of polypharmacy, a single consultation between general practitioner and cardiologist would be more effective. For control of the rate of ventricular contraction during the treatment of AF, lipophilic beta-blockers are preferable to hydrophilic beta-blockers because the pharmacokinetics in elderly people are substantially different. When there is a high risk of thrombo-embolic complications with AF, treatment with coumarin derivatives is advised. However, little research has been done on this subject among elderly people in a general practice setting. In this age group, the risk of complications due to treatment with coumarin derivatives is sometimes higher than the advantages it offers. This is why the GP should always consider carefully whether or not elderly people with AF should be treated with coumarin derivatives.

Age Factors↗

[The practice guideline 'Peripheral vascular disease' (first revision) from the Dutch College of General Practitioners: a response from the perspective of general practice].

The practice guideline 'Peripheral vascular disease' (PVD) from the Dutch College of General Practitioners will certainly be of benefit to the Dutch general practitioner. Its limited set of simple diagnostic steps can help the general practitioner to assess or exclude PVD in patients with intermittent claudication. The inclusion of a pretest-posttest probability scheme enhances a clear diagnostic process. This guideline differs from the previous one in one important aspect. This guideline deals not only with the specific management of peripheral arterial disease but also with the management of cardiovascular risk in general. In this way the guideline follows the recently changed international attitude reflected in the European Guidelines on cardiovascular disease prevention. Smoking cessation and exercise therapy continues to be the cornerstone as well as the stumbling block of management of most cases of PVD in general practice; a challenge for every general practitioner.

Exercise Therapy↗

[The practice guideline 'Stable angina pectoris' (second revision) from the Dutch College of General Practitioners; a response from the perspective of general practice].

The Dutch College of General Practitioners' (Dutch acronym: NHG) practice guideline 'Stable angina pectoris' (second revision) provides clear guidelines for the diagnosis and treatment of patients who experience chest pains as a result of angina pectoris, especially if coronary artery disease is the underlying cause of the complaints. The practice guideline clearly indicates for which complaints the general practitioner should suspect angina pectoris and which information from the anamnesis, family history and risk factors can contribute to distinguishing between stable and unstable angina pectoris. However, the physical examination should not be omitted because this can provide important indications for coronary or pulmonary dysfunction. According to the practice guideline, the treatment policy is determined by the estimated risk of significant coronary artery disease. However, additional tests can be useful even in the case of a small risk, as these can reassure patients. The indications and contraindications for medicinal substances are clearly presented.

Angina Pectoris↗