Biomedical subjects

C Wagner

Publications and source records attributed to C Wagner.

At least 55 records · Page 3Linked to original sources

PubMed2002

[Dentists and mutual practice visitation. Results of a descriptive study on the effects on mutual visitation by dentists].

In 1998 mutual practice visitation has been introduced in the Dutch dental practice as a method to improve quality of dental care. The method is called 'mutual visitation' because groups of three dentists visit and evaluate each others practices. An independent research institute (Nivel) investigated the perceived effects, advantages and barriers of visitation. A postal questionnaire was sent to all 235 dentists who, by that time, participated in visitation. The response was 57%. The results showed that the effects reported most frequently were: a more critical attitude to dental practice, more insight into practices of colleagues and actual improvements in dental care. The majority of the respondents considered visitation suitable to improve practice-organization. A minority considered visitation suitable to increase professional expertise. The mutuality of the visitation was highly valued by the participants. The main disadvantage of visitation appeared to be the time investment (a mean of three days per dentist). In general, the respondents held the view that the positive effects outweighed the time and efforts, however, many dentists regretted the lack of financial compensation for visitation.

Adult↗

PubMed2001

Dimerization of the 3'UTR of bicoid mRNA involves a two-step mechanism.

The proper localization of bicoid (bcd) mRNA requires cis-acting signals within its 3' untranslated region (UTR) and trans-acting factors such as Staufen. Dimerization of bcd mRNA through intermolecular base-pairing between two complementary loops of domain III of the 3'UTR was proposed to be important for particle formation in the embryo. The participation in the dimerization process of each domain building the 3'UTR was evaluated by thermodynamic and kinetic analysis of various mutated and truncated RNAs. Although sequence complementarity between the two loops of domain III is required for initiating mRNA dimerization, the initial reversible loop-loop complex is converted rapidly into an almost irreversible complex. This conversion involves parts of RNA outside of domain III that promote initial recognition, and dimerization can be inhibited by sense or antisense oligonucleotides only before conversion has proceeded. Injection of the different bcd RNA variants into living Drosophila embryos shows that all elements that inhibit RNA dimerization in vitro prevent formation of localized particles containing Staufen. Particle formation appeared to be dependent on both mRNA dimerization and other element(s) in domains IV and V. Domain III of bcd mRNA could be substituted by heterologous dimerization motifs of different geometry. The resulting dimers were converted into stable forms, independently of the dimerization module used. Moreover, these chimeric RNAs were competent in forming localized particles and recruiting Staufen. The finding that the dimerization domain of bcd mRNA is interchangeable suggests that dimerization by itself, and not the precise geometry of the intermolecular interactions, is essential for the localization process. This suggests that the stabilizing interactions that are formed during the second step of the dimerization process might represent crucial elements for Staufen recognition and localization.

3' Untranslated Regions↗

PubMed2001

[Laparoscopic gastric banding in therapy of obesity. Which patients benefit?].

In view of concomitant illnesses and sequelae associated with significantly increased morbidity and mortality, obesity is considered a major pathological condition. The aim of treatment must be the lasting reduction of overweight. The prerequisite for this is a fundamental change in the patient's inappropriate eating habits, as also other lifestyle aspects. This requires comprehensive and long-term disciplinary management. Within this framework, surgical treatment, in particular the laparoscopic placement of an adjustable gastric band, is the most effective form of achieving weight reduction. The band delays passage of food, and causes early distension of the stomach wall, thus inducing a sensation of satiety. To ensure therapeutic success, nutritional and surgical counseling of the patient has a major role to play.

Body Mass Index↗

PubMed2001

Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine.

Methionine adenosyltransferase (MAT) is an essential enzyme that catalyzes the synthesis of S-adenosylmethionine (AdoMet), the most important biological methyl donor. Liver MAT I/III is the product of the MAT1A gene. Hepatic MAT I/III activity and MAT1A expression are compromised under pathological conditions such as alcoholic liver disease and hepatic cirrhosis, and this gene is silenced upon neoplastic transformation of the liver. In the present work, we evaluated whether MAT1A expression could be targeted by the polycyclic arylhydrocarbon (PAH) 3-methylcholanthrene (3-MC) in rat liver and cultured hepatocytes. MAT1A mRNA levels were reduced by 50% following in vivo administration of 3-MC to adult male rats (100 mg/kg, p.o., 4 days' treatment). This effect was reproduced in a time- and dose-dependent fashion in cultured rat hepatocytes, and was accompanied by the induction of cytochrome P450 1A1 gene expression. This action of 3-MC was mimicked by other PAHs such as benzo[a]pyrene and benzo[e]pyrene, but not by the model arylhydrocarbon receptor (AhR) activator 2,3,7,8-tetrachlorodibenzo-p-dioxin. 3-MC inhibited transcription driven by a MAT1A promoter-reporter construct transfected into rat hepatocytes, but MAT1A mRNA stability was not affected. We recently showed that liver MAT1A expression is induced by AdoMet in cultured hepatocytes. Here, we observed that exogenously added AdoMet prevented the negative effects of 3-MC on MAT1A expression. Taken together, our data demonstrate that liver MAT1A gene expression is targeted by PAHs, independently of AhR activation. The effect of AdoMet may be part of the protective action of this molecule in liver damage.

Animals↗

PubMed2001

On the role of conserved histidine 106 in 10-formyltetrahydrofolate dehydrogenase catalysis: connection between hydrolase and dehydrogenase mechanisms.

The enzyme, 10-formyltetrahydrofolate dehydrogenase (FDH), converts 10-formyltetrahydrofolate (10-formyl-THF) to tetrahydrofolate in an NADP(+)-dependent dehydrogenase reaction or an NADP(+)-independent hydrolase reaction. The hydrolase reaction occurs in a 310-amino acid long amino-terminal domain of FDH (N(t)-FDH), whereas the dehydrogenase reaction requires the full-length enzyme. The amino-terminal domain of FDH shares some sequence identity with several other enzymes utilizing 10-formyl-THF as a substrate. These enzymes have two strictly conserved residues, aspartate and histidine, in the putative catalytic center. We have shown recently that the conserved aspartate is involved in FDH catalysis. In the present work we studied the role of the conserved histidine, His(106), in FDH function. Site-directed mutagenesis experiments showed that replacement of the histidine with alanine, asparagine, aspartate, glutamate, glutamine, or arginine in N(t)-FDH resulted in expression of insoluble proteins. Replacement of the histidine with another positively charged residue, lysine, produced a soluble mutant with no hydrolase activity. The insoluble mutants refolded from inclusion bodies adopted a conformation inherent to the wild-type N(t)-FDH, but they did not exhibit any hydrolase activity. Substitution of alanine for three non-conserved histidines located close to the conserved one did not reveal any significant changes in the hydrolase activity of N(t)-FDH. Expressed full-length FDH with the substitution of lysine for the His(106) completely lost both the hydrolase and dehydrogenase activities. Thus, our study showed that His(106), besides being an important structural residue, is also directly involved in both the hydrolase and dehydrogenase mechanisms of FDH. Modeling of the putative hydrolase catalytic center/folate-binding site suggested that the catalytic residues, aspartate and histidine, are unlikely to be adjacent to the catalytic cysteine in the aldehyde dehydrogenase catalytic center. We hypothesize that 10-formyl-THF dehydrogenase reaction is not an independent reaction but is a combination of hydrolase and aldehyde dehydrogenase reactions.

Amino Acid Sequence↗

PubMed2001

Mutagen sensitivity of nasopharyngeal cancer patients.

Primary nasopharyngeal carcinomas (NPCs) may be of various types, including squamous cell carcinomas, undifferentiated carcinomas, and lymphoepitheliomas. Tumor initiation has been linked to the Epstein-Barr virus and, in some geographical regions, to alimentary factors. Possible hereditary components for the appearance of NPCs have not yet been clearly identified. In this study, genetic sensitivity to the genotoxic effects of carcinogenic xenobiotics as an endogenous risk factor of tumor initiation was investigated. The single cell microgel electrophoresis assay was used to quantify chemically-induced DNA damage in lymphocytes of 30 NPC patients and 30 non-tumor donors. The xenobiotics investigated were N'-nitrosodiethylamine, sodium dichromate, and nickel sulphate, with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and dimethyl sulfoxide (DMSO) as positive and negative controls, respectively. The extent of DNA migration in the solvent control cultures was not significantly different between the two groups (1.2+/-0.5 mean Olive tail moment and standard deviation of 30 individuals for NPC patients; 1.1+/-0.4 for non-tumor donors). With constant exposure and electrophoretic conditions, genotoxic effects of varying degrees were induced by the different xenobiotics in tumor and non-tumor patients (nickel sulphate: 7.1+/-2.5 for NPC patients and 5.9+/-1.6 for non-tumor donors; sodium dichromate: 18.1+/-5.3 for NPC patients and 16.2+/-5.4 for non-tumor donors; MNNG: 47.8+/-13.3 for NPC patients and 52.7+/-13.6 for non-tumor donors). Only N'-nitrosodiethylamine proved to induce significantly more DNA migration in lymphocytes of tumor patients (9.8+/-3.1) as compared to non-tumor patients (8.2+/-2.3). Although for sodium dichromate the degree of DNA migration did not significantly differ, variability in migration patterns proved to be lower in the tumor group. Mutagen sensitivity of NPC patients was shown to be elevated for a selected xenobiotic, whereas a general elevation of DNA fragility was not present. Further studies on mutagen sensitivity as an endogenous risk factor influencing the susceptibility of patients at the time of first diagnosis of nasopharyngeal carcinomas are warranted.

Adult↗

PubMed2001

Amplitude measurements of Faraday waves.

A light reflection technique is used to measure quantitatively the surface elevation of Faraday waves. The performed measurements cover a wide parameter range of driving frequencies and sample viscosities. In the capillary wave regime the bifurcation diagrams exhibit a frequency independent scaling proportional to the wavelength. We also provide numerical simulations of the full Navier-Stokes equations, which are in quantitative agreement up to supercritical drive amplitudes of epsilon approximately equal 20%. The validity of an existing perturbation analysis is found to be limited to epsilon<2.5%.

Journal Article↗

PubMed2001

The complement receptor 3, CR3 (CD11b/CD18), on T lymphocytes: activation-dependent up-regulation and regulatory function.

The complement receptor 3 (CR3; CD11b/CD18) is present exclusively on leukocytes, particularly on NK cells, monocytes and polymorphonuclear neutrophils. Approximately 10% of peripheral T lymphocytes and, as we found now mainly CD8(+) cells, expressed CD11b. Upon stimulation, however, expression of CD11b was up-regulated also on CD4(+) cells. Stimulation of T cells either by cross-linked anti-CD3 and IL-2 or by mononuclear cells and mitogen yielded up to 28% CD11b(+) T cells. The majority of CD11b(+) T cells also expressed CD56. T cell lines established from healthy donors were also found to express CR3. When restimulated up to 90% of cells became positive for CD11b making those cells an ideal tool for studying the functional role of CD11b. Antibodies to CD11b and bona fide ligands for the complement receptor inhibited the anti-CD3-induced T cell proliferation and as well as IL-2 release. In contrast, proliferation of a CD11b(-) T cell line was not inhibited. Taken together, our data indicate an activation-dependent expression of the complement receptor on T cells and suggest a regulatory function.

Amino Acid Sequence↗

PubMed2001

Transdifferentiation of polymorphonuclear neutrophils: acquisition of CD83 and other functional characteristics of dendritic cells.

Polymorphonuclear neutrophils (PMN) are in the first line of defense against bacterial infections. They are considered to be end-differentiated cells undergoing constitutive apoptosis within hours after release from the bone marrow. During pathological events, however, their life span is extended in conjunction with morphological and functional alterations indicative of a transdifferentiation of mature PMN. To further characterize differentiated PMN, the alterations seen in vivo were reproduced by cultivating PMN of healthy donors with either gamma-interferon, granulocyte/macrophage colony stimulating factor, or a combination thereof. Thus cultivated cells escaped from apoptosis, and protein synthesis was induced, notably of the major histocompatibility complex (MHC) class II antigens, CD80 and CD86. Moreover, CD83, thought to be specific for dendritic cells was synthesized, while typical markers of PMN, including CD66b, CD11a/CD11b/CD11c, CD15, CD18 were preserved. A profound alteration of both cellular morphology and of function was seen: the cultivated PMN lost their chemotactic activity but had acquired the ability to present to T-cells a peptide antigen in a MHC class II restricted manner. The data lead to the conclusion that mature PMN can differentiate further to cells with characteristics of DCs, thereby connecting PMN to the specific T-cell response.

Antigen Presentation↗

PubMed2001

[Virtual reality in ophthalmological education].

We present a computer-based medical training workstation for the simulation of intraocular eye surgery. The surgeon manipulates two original instruments inside a mechanical model of the eye. The instrument positions are tracked by CCD cameras and monitored by a PC which renders the scenery using a computer-graphic model of the eye and the instruments. The simulator incorporates a model of the operation table, a mechanical eye, three CCD cameras for the position tracking, the stereo display, and a computer. The three cameras are mounted under the operation table from where they can observe the interior of the mechanical eye. Using small markers the cameras recognize the instruments and the eye. Their position and orientation in space is determined by stereoscopic back projection. The simulation runs with more than 20 frames per second and provides a realistic impression of the surgery. It includes the cold light source which can be moved inside the eye and the shadow of the instruments on the retina which is important for navigational purposes.

Computer Graphics↗

PubMed2001

The impact of legislative versus non-legislative quality policy in health care: a comparison between two countries.

UNLABELLED: An important aim of the government's quality policy is to stimulate quality management (QM) in health care organizations. The relationship between the government's quality policy and QM in health care organizations is unknown. This article explores that relationship by comparing two countries with different quality policies, The Netherlands and Finland. In The Netherlands QM is required by law and health care is organized at national level. In Finland, QM is not required by law and the responsibilities for organizing health care are delegated to the municipalities. The question is whether or not these differences in national policy are reflected in the extent and effectiveness of QM in health care organizations in the two countries. A cross sectional survey was conducted in late 1999. Data about QM in both countries were gathered by questionnaire. The subsectors involved were hospitals, care for the disabled and care for the elderly. A total of 1172 health care organizations participated in the study (response rate 64%). The results show that-in keeping with our hypothesis-slightly more QM-activities and more patient participation were found in Dutch health care organizations compared with the Finnish ones. However, contrary to our expectations, the Finnish organizations reported more perceived effects of their QM-activities. Further analyses showed that some QM-activities are more closely related to the effectiveness of QM than others. In particular, cyclic quality improvement procedures, human resource management and the flexible attitude of employees showed the strongest relationship with the perceived effects of QM. The difference between the national approach in The Netherlands and the decentralized approach in Finland did not, as we had assumed, result in more regional variation in QM in Finland. CONCLUSIONS: a government's quality policy may have some influence on the extent of QM in health care organizations. However, more QM-activities do not necessarily imply more effects. RECOMMENDATIONS: since QM-activities differ in the degree to which they bring about changes and improvements in care, it is recommended that policy makers promote those QM-activities, which are the most potent, in order to improve the quality of care.

Aged↗

PubMed2001

Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia.

This paper reports clinical and metabolic studies of two Italian siblings with a novel form of persistent isolated hypermethioninaemia, i.e. abnormally elevated plasma methionine that lasted beyond the first months of life and is not due to cystathionine beta-synthase deficiency, tyrosinaemia I or liver disease. Abnormal elevations of their plasma S-adenosylmethionine (AdoMet) concentrations proved they do not have deficient activity of methionine adenosyltransferase I/III. A variety of studies provided evidence that the elevations of methionine and AdoMet are not caused by defects in the methionine transamination pathway, deficient activity of methionine adenosyltransferase II, a mutation in methylenetetrahydrofolate reductase rendering this activity resistant to inhibition by AdoMet, or deficient activity of guanidinoacetate methyltransferase. Plasma sarcosine (N-methylglycine) is elevated, together with elevated plasma AdoMet in normal subjects following oral methionine loads and in association with increased plasma levels of both methionine and AdoMet in cystathionine beta-synthase-deficient individuals. However, plasma sarcosine is not elevated in these siblings. The latter result provides evidence they are deficient in activity of glycine N-methyltransferase (GNMT). The only clinical abnormalities in these siblings are mild hepatomegaly and chronic elevation of serum transaminases not attributable to conventional causes of liver disease. A possible causative connection between GNMT deficiency and these hepatitis-like manifestations is discussed. Further studies are required to evaluate whether dietary methionine restriction will be useful in this situation.

Alanine Transaminase↗

PubMed2001

Hyaluronan-independent adhesion of CD44H+ and CD44v10+ lymphocytes to dermal microvascular endothelial cells and keratinocytes.

We have recently shown the CD44 variant isoform 10 (CD44v10) to be expressed on reactive as well as malignant cutaneous lymphocytes; however, the functional consequences of CD44v10 expression on lymphocytes are not elucidated. By using appropriately transfected lymphatic cells we analyzed the role of CD44v10 on lymphocytes in cell-matrix adhesion and homotypic and heterotypic cell-cell adhesion assays. Despite a low binding affinity to hyaluronan, CD44v10-expressing lymphocytes exhibited heterotypic cell-cell adhesion to inflamed dermal microvascular endothelium and keratinocytes, as indicated by Stamper-Woodruff assays on tissue sections of delayed type hypersensitivity reactions and adhesion assays with cultured keratinocytes and cytokine-stimulated human dermal microvascular endothelial cells. Antibody-blocking assays excluded interaction of CD44v10 with the principal CD44 ligand hyaluronan as well as involvement of selectins or integrins in these heterotypic cell-cell adhesion assays. In contrast, cellular aggregation assays with fluorescence-labeled CD44v10- and CD44H-expressing lymphocytes revealed homotypic CD44v10/CD44v10 binding as well as binding of CD44v10 with CD44H. Heterotypic cell-cell adhesion assays with ultraviolet-A-irradiated CD44v-negative cytokine-stimulated endothelial cells demonstrated binding kinetics of CD44v10-expressing lymphocytes paralleling those of endothelial CD44H expression. These results imply that a hyaluronan-independent CD44v10/CD44H-mediated pathway is involved in lymphocyte infiltration into the dermis and epidermis of inflamed skin and suggest modulation of CD44H expression on inflamed dermal microvascular endothelium as a mechanism of ultraviolet-A-induced therapeutic effects on the skin.

Cell Adhesion↗

PubMed2001

Infliximab induces potent anti-inflammatory and local immunomodulatory activity but no systemic immune suppression in patients with Crohn's disease.

BACKGROUND: Anti-TNFalpha therapy with infliximab is effective for Crohn's disease. Infliximab neutralizes the biological activities of TNFalpha, a cytokine involved in host-defence against certain infections. AIM: To evaluate the effects of infliximab on the gut and peripheral immune system functions. METHODS: Biopsies and blood samples from three clinical trials of infliximab in Crohn's disease were analysed. Pharmacokinetics, changes in leucocyte counts and T cell subsets, T cell function, and cytokine profiles of lamina propria mononuclear cells (LPMC) and peripheral blood mononuclear cells (PBMC) were analysed. RESULTS: Infliximab has a serum half-life of 9.5 days and is still detectable in serum 8 weeks after infusion. Leucocyte counts showed consistent changes from baseline toward normal values after therapy. Monocytes and lymphocytes were modestly increased, while neutrophils were decreased 4 weeks after treatment. Lymphocyte subsets and T cell proliferative responses were not altered after therapy. The proportion of PBMCs capable of producing IFNgamma and TNFalpha did not change, while Th1 cytokine production by stimulated LPMC was decreased after infliximab therapy. CONCLUSION: The clinical efficacy of infliximab is based on local anti-inflammatory and immunomodulatory effects in the bowel mucosa, without generalized suppression of systemic immune functions in Crohn's disease patients.

Antibodies, Monoclonal↗

PubMed2001

The negative regulator Opi1 of phospholipid biosynthesis in yeast contacts the pleiotropic repressor Sin3 and the transcriptional activator Ino2.

Structural genes of phospholipid biosynthesis in the yeast Saccharomyces cerevisiae are transcriptionally co-regulated by ICRE (inositol/choline-responsive element) promoter motifs. Gene activation by an ICRE is mediated by binding of the Ino2/Ino4 transcription factor, whereas repression in the presence of high concentrations of inositol and choline (IC) requires an intact Opi1 repressor. However, the mechanism of specific repression and the functional interplay among these regulators remained unclear from previous work. Using in vivo as well as in vitro interaction assays, we show binding of the pleiotropic repressor Sin3 to the pathway-specific regulator Opi1. The paired amphipathic helix 1 (PAH1) within Sin3 and OSID (Opi1-Sin3 interaction domain) in the N-terminus of Opi1 were mapped as contact sites. The regulatory significance of the Opi1-Sin3 interaction was shown by the obvious deregulation of an ICRE-dependent reporter gene in a sin3 mutant. Opi1 also interacts with a newly identified functional domain of the transcriptional activator Ino2 (RID, repressor interaction domain). These results define the molecular composition of the transcription complex mediating control of ICRE-dependent genes and allow a hypothesis on the flow of regulatory information in response to phospholipid precursors.

Amino Acid Sequence↗

PubMed2001

Polymorphonuclear neutrophils in Wegener's granulomatosis acquire characteristics of antigen presenting cells.

BACKGROUND: Constitutive expression of major histocompatibility complex (MHC) class II antigens and of the co-stimulatory receptors CD80 and CD86 is restricted to professional antigen presenting cells. Polymorphonuclear neutrophils (PMN) of healthy donors are negative for those antigens. Our recent study, however, found that PMN of patients with active Wegener's granulomatosis acquired MHC class II antigens. METHODS: To continue and extend the previous study results, PMN and monocytes of 60 patients with Wegener's granulomatosis, 24 patients with microscopic polyangiitis (MPA), 20 patients with acute bacterial infection, and 53 healthy donors were analyzed for the expression of MHC class II antigens as well as of CD80 and CD86. Moreover, induction on PMN of MHC class II expression was studied, as was antigen presentation as a possible functional consequence. RESULTS: PMN of patients with acute, active Wegener's granulomatosis expressed MHC class II antigens, CD80 and CD86; on monocytes up-regulation of MHC class II was seen. In contrast, PMN of patients with inactive disease, or with relapse, patients with microscopic polyangiitis or with bacterial infections expressed neither MHC class II, nor CD80 or CD86. PMN of healthy donors acquired these antigens when cultured in the presence of T cells or T cell-derived cytokines. The PMN were then able to present to T cell antigens in a MHC-class II restricted manner. CONCLUSION: During active disease, the PMN of patients with Wegener's granulomatosis acquire characteristics of antigen presenting cells, whereas the PMN of patients with MPA or bacterial infection do not. The finding reflects differences in the pattern of the respective inflammatory response and suggests new effector functions of PMN. Moreover, MHC class II expression on PMN could serve as a novel marker for active Wegener's granulomatosis.

Adult↗

PubMed2001

Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine.

BACKGROUND: Although plasma total homocysteine has been identified as an independent risk factor for vascular disease in a multitude of studies, there is a considerable overlap in values between patients at risk and control subjects. The difference in values can be used to distinguish statistically between the 2 groups, provided each group is large enough; however, discriminating between individual patients at risk and control subjects is difficult. OBJECTIVE: We investigated whether the precursor of homocysteine, S-adenosylhomocysteine, is a more sensitive indicator of risk. DESIGN: We measured plasma total homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, creatinine, folate, and vitamin B-12 in 30 patients with proven cardiovascular disease and 29 age- and sex-matched control subjects. RESULTS: The homocysteine values (+/-SD) were 12.8 +/- 4.9 (95% CI: 11.0, 14.7) micromol/L for patients and 11.0 +/- 3.2 (9.8, 12.2) micromol/L for control subjects. The S-adenosylhomocysteine values were 40.0 +/- 20.6 (32.3, 47.7) nmol/L for patients and 27.0 +/- 6.7 (24.5, 30.0) nmol/L for control subjects (P = 0.0021). The S-adenosylmethionine values were 121.8 +/- 42.9 (105.8, 137.8) nmol/L for patients and 103.9 +/- 21.8 (95.6, 112.2) nmol/L for control subjects (P = 0.0493). The creatinine values were 110 +/- 27 (97, 120) micromol/L for patients and 97 +/- 9 (80, 100) micromol/L for control subjects (P = 0.0025). Values for folate and vitamin B-12 did not differ significantly between groups. CONCLUSIONS: Plasma S-adenosylhomocysteine appears to be a much more sensitive indicator of the difference between patients with cardiovascular disease and control subjects than is homocysteine. Both plasma total homocysteine and S-adenosylhomocysteine are significantly correlated with plasma creatinine in patients.

Adult↗

PubMed2001

A programmed ependymal denudation precedes congenital hydrocephalus in the hyh mutant mouse.

Hydrocephalic hyh mice are born with moderate hydrocephalus and a normal cerebral aqueduct. At about the fifth postnatal day the aqueduct becomes obliterated and severe hydrocephalus develops. The aim of the present investigation was to investigate the mechanism of this hydrocephalus, probably starting during fetal life when the cerebral aqueduct is still patent. By use of immunocytochemistry and scanning electron microscopy, mutant (n = 54) and normal (n = 61) hyh mouse embryos were studied at various developmental stages to trace the earliest microscopic changes occurring in the brains of embryos becoming hydrocephalic. The primary defect begins at an early developmental stage (E-12) and involves cells lining the brain cavities, which detach following a well-defined temporo-spatial pattern. This ependymal denudation mostly involves the ependyma of the basal plate derivatives. There is a relationship between ependymal denudation and ependymal differentiation evaluated by the expression of vimentin and glial fibrillary acidic protein. The ependymal cells had a normal appearance before and after detachment, suggesting that their separation from the ventricular wall might be due to abnormalities in cell adhesion molecules. The process of detachment of the ventral ependyma, clearly visualized under scanning electron microscope, is almost completed before the onset of hydrocephalus. Furthermore, this ependymal denudation does not lead to aqueductal stenosis during prenatal life. Thus, the rather massive ependymal denudation appears to be the trigger of hydrocephalus in this mutant mouse, raising the question about the mechanism responsible for this hydrocephalus. It seems likely that an uncontrolled bulk flow of brain fluid through the extended areas devoid of ependyma may be responsible for the hydrocephalus developed by the hyh mutant embryos. The defect in these embryos also includes loss of the hindbrain floor plate and a delayed in the expression of Reissner fiber glycoproteins by the subcommissural organ.

Animals↗