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Biomedical subjects

M Meyer

Publications and source records attributed to M Meyer.

At least 217 records · Page 12Linked to original sources

Strategies towards a better understanding of antibiotic action: folate pathway inhibition in Haemophilus influenzae as an example.

Two-dimensional electrophoresis was applied to the global analysis of the cellular response of Haemophilus influenzae to sulfamethoxazole and trimethoprim, both inhibitors of tetrahydrofolate synthesis. Deregulation of the synthesis rate of 118 proteins, involved in different metabolic pathways, was observed. The regulation of the genes involved in the metabolism of the amino acids methionine, threonine, serine, glycine, and aspartate was investigated in detail by analysis of protein synthesis and Northern hybridization. The results suggested that the synthesis of methionine biosynthetic enzymes in H. influenzae is regulated in a similar fashion as in Escherichia coli. A good correlation between the results obtained by Northern hybridization and quantification of protein synthesis was observed. In contrast to trimethoprim, sulfamethoxazole triggered the increased synthesis of the heat shock proteins DnaK, GroEL, and GroES.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

Maturation of phagosomes is accompanied by specific patterns of small GTPases.

In this study we purified phagosomes of the ciliated protozoan Tetrahymena thermophila to analyze aspects of the maturation pathway of phagocytotic vesicles. Phagosomes were labeled with magnetic microparticles and then purified in high amounts with the help of a permanent magnet. By combining a pulse-chase labeling protocol with the magnetic separation procedure we were able to isolate phagosomes of defined ages, which represent distinct stages of their maturation pathway. GTP-overlay assays showed that a set of small GTPases of the ras superfamily is associated with these phagosomes. Phagosomes isolated at different stages of maturation revealed a change in the pattern of the small GTPases. Some small GTPases identified by the GTPase overlay assays could be aligned to India ink stained protein spots in two-dimensional gels of isolated phagosomes. The results presented here are a first step to identify the members of small GTPases associated with phagosomes during their maturation pathway. Microsequencing of pooled polypeptides by mass-spectrometric techniques will identify the primary structure of these small GTPases.

Animals↗

Frequency-dependence of myocardial energetics in failing human myocardium as quantified by a new method for the measurement of oxygen consumption in muscle strip preparations.

Diastolic dysfunction at high heart rates may be associated with increased myocardial energy consumption. Frequency-dependent changes of isometric force and oxygen consumption (MVO2) were investigated in strip preparations from endstage failing human hearts exhibiting various degrees of diastolic dysfunction. MVO2 was determined by a new method which was validated. When stimulation rate was increased from 40 to 200 min-1 (n=7), developed force decreased from 16.5+/-4.3 to 7.9+/-2.9 mN/mm2 (P<0.01), diastolic force increased from 15.9+/-3.2 to 22.0+/-3.0 mN/mm2 (P<0.01), and total MVO2 increased from 2.6+/-0.6 to 4.7+/-0.9 ml/min/100 g (P<0.025). Resting MVO2 and resting force were 1.8+/-0.4 ml/min/100 g and 15.9+/-3.0 mN/mm2, respectively. After addition of 30 mm 2,3-butanedione monoxime (BDM) to inhibit crossbridges, resting MVO2 and resting force decreased by 46% (P<0.05) and 15% (P<0.01), respectively, indicating the presence of active force generation in unstimulated failing human myocardium. In each muscle preparation, there was a significant correlation between force-time integral (FTI) and total MVO2 (r=0.96+/-0.01). The strength of these correlations did not vary with the contribution of diastolic FTI to total FTI. The ratio of activity related MVO2 to developed FTI, an inverse index of the economy of contraction, increased depending on the rise of diastolic FTI at higher stimulation rates. In conclusion, in failing human myocardium, diastolic force development is occurring at the same energy expenditure as systolic force generation. Therefore, in muscle preparations with disturbed diastolic function economy of contraction decreases with higher stimulation rates, depending on the rise of diastolic force.

Biomechanical Phenomena↗

Sphincter preservation with chemoradiation in anal canal carcinoma: abdominoperineal resection in selected cases?

PURPOSE: This study contained herein assessed long-term results, toxicity, and prognostic variables following combined modality therapy of patients with International Union Against (Cancer Classification T1-4, N0-3, M0 squamous-cell carcinoma of the anal canal. PATIENTS AND METHODS: Between 1985 and 1996, 62 patients completed treatment with combined modality therapy. A median total dose of 50 Gy was given to the primary, perirectal, presacral, and inguinal nodes followed by a local boost in selected cases. 5-Fluorouracil was scheduled as a continuous infusion of 1,000 mg/m2 per 24 hours on days 1 to 5 and 29 to 33 and mitomycin C as a bolus of 10 mg/m2 on days 1 and 29. Routinely processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferating cell nuclear antigen and MIB1 (Ki-67) antigen to determine the labeling index. In addition, DNA ploidy was assessed after Feulgen staining. RESULTS: Actuarial cancer-related survival, no evidence of disease survival, and colostomy-free survival rates at five years were 81, 76, and 86 percent, respectively. In univariate analysis, T category (T1/2 vs. T3/4) was predictive for no evidence of disease survival (87 vs. 59 percent; P = 0.03) and colostomy-free survival (94 vs. 73 percent; P = 0.05). N category (N0 vs. N1-3) influenced actuarial cancer-related survival (85 vs. 58 percent; P = 0.002) and no evidence of disease survival (80 vs. 53 percent; P = 0.02). A higher proliferative potential as measured by the MIB1 labeling index was associated with a better colostomy-free survival (90 vs. 50 percent; P = 0.04). In multivariate analysis, actuarial cancer-related survival was only influenced by the N category (P = 0.03) and no evidence of disease survival by N category (P = 0.03) and mitomycin C dose (P = 0.04). Salvage abdominoperineal resection achieved long-term control in only four of seven patients with local failures. CONCLUSION: Treatment with a combination of radiotherapy and chemotherapy is safe and effective for patients with anal canal carcinoma. Abdominoperineal resection is indicated as a salvage procedure in nonresponding and recurrent lesions and may be of benefit in a small subgroup of patients with poor prognostic factors.

Adult↗

[Remission ratio of chronic urticaria--"spontaneous" healing or result of eradication of Helicobacter pylori?].

Helicobacter pylori infection has been assumed to be the underlying cause of some dermatological diseases such as, chronic urticaria. In order to investigate this problem we interviewed 55 patients with chronic urticaria concerning the state of the disease approximately 10 months after being discharged from hospital. After an additional six months we interviewed them for a second time and thus determined the remission ratio. There was no significant evidence showing that a link exists between urticaria and proven Helicobacter pylori infection (chi 2-Test). There was also no significant correlation in the remission ratio between patients treated with a triple therapy and non-treated patients (exact Fisher-Test).

Chronic Disease↗

Comparison of mesencephalic free-floating tissue culture grafts and cell suspension grafts in the 6-hydroxydopamine-lesioned rat.

Ventral mesencephalon (VM) of fetal rat and human origin grown as free-floating roller-tube (FFRT) cultures can survive subsequent grafting to the adult rat striatum. To further explore the functional efficacy of such grafts, embryonic day 13 ventral mesencephalic tissue was grafted either after 7 days in culture or directly as dissociated cell suspensions, and compared with regard to neuronal survival and ability to normalize rotational behavior in adult rats with unilateral 6-hydroxydopamine (6-OHDA) lesions. Other lesioned rats received injections of cell-free medium and served as controls. The amphetamine-induced rotational behavior of all 6-OHDA-lesioned animals was monitored at various time points from 18 days before transplantation and up to 80 days after transplantation. Tyrosine hydroxylase (TH) immunostaining of the histologically processed brains served to assess the long-term survival of grafted dopaminergic neurons and to correlate that with the behavioral effects. Additional cultures and acutely prepared explants were also fixed and stored for histological investigation in order to estimate the loss of dopaminergic neurons in culture and after transplantation. Similar behavioral improvements in terms of significant reductions in amphetamine-induced rotations were observed in rats grafted with FFRT cultures (127%) and rats grafted with cell suspensions (122%), while control animals showed no normalization of rotational behavior. At 84 days after transplantation, there were similar numbers of TH-immunoreactive (TH-ir) neurons in grafts of cultured tissue (775 +/- 98, mean +/- SEM) and grafts of fresh, dissociated cell suspension (806 +/- 105, mean +/- SEM). Cell counts in fresh explants, 7-day-old cultures, and grafted cultures revealed a 68.2% loss of TH-ir cells 7 days after explantation, with an additional 23.1% loss after grafting, leaving 8.7% of the original number of TH-ir cells in the intracerebral grafts. This is to be compared with a survival rate of 9.1% for the TH-ir cells in the cell-suspension grafts. Immunostaining for the calcium-binding proteins calretinin, calbindin, and parvalbumin showed no differences in the neuronal expression of these proteins between the two graft types. In conclusion, we found comparable dopaminergic cell survival and functional effects of tissue-culture grafts and cell-suspension grafts, which currently is the type of graft most commonly used for experimental and clinical grafting. In this sense the result is promising for the development of an effective in vitro storage of fetal nigral tissue, which at the same time would allow neuroprotective and neurotrophic treatment prior to intracerebral transplantation.

Amphetamine↗

Hippocampal mossy fiber sprouting is not impaired in brain-derived neurotrophic factor-deficient mice.

In human temporal lobe epilepsy, a loss of hilar neurons followed by the sprouting of recurrent mossy fiber collaterals and the reinnervation of free synaptic sites on granule cell dendrites are discussed as possible mechanisms underlying hippocampal hyperexcitability. Dentate granule cells have been shown to upregulate brain-derived neurotrophic factor (BDNF) as well as TrkB, the high-affinity receptor for BDNF, in response to limbic seizures. This raised the possibility that BDNF is an important factor in hippocampal mossy fiber sprouting. Here we have used slice cultures of hippocampus, in which mossy fibers sprout and form a supragranular plexus in response to granule cell deafferentation, and have compared cultures from early postnatal BDNF-deficient mice and wild-type mice. We demonstrate that there is sprouting of supragranular mossy fibers in cultured slices from both BDNF knock-out and wild-type mice. We conclude that BDNF is not an essential factor for mossy fiber sprouting. However, our data do not exclude a role for BDNF in mossy fiber sprouting in wild-type mice, as compensatory mechanisms might have become effective in the mutant.

Animals↗

Influence of SR Ca(2+)-ATPase and Na(+)-Ca(2+)-exchanger on the force-frequency relation.

The data presented indicate that altered systolic and diastolic function in failing human hearts may result from altered expression of calcium cycling proteins. Decreased systolic force production and inversion of the force-frequency relation seem to be related to reduced protein levels of SR Ca2+ ATPase and/or to increased protein levels of the Na(+)-Ca2+ exchanger resulting in an increased ratio of Na(+)-Ca2+ exchanger to SR Ca2+ ATPase. Impaired diastolic function may result from reduced SR Ca2+ ATPase and is most pronounced in failing hearts with lack of upregulation of the Na(+)-Ca2+ exchanger. Thus, failing hearts with reduced SR Ca2+ ATPase protein levels and unchanged Na(+)-Ca2+ exchanger protein levels exhibit severe impairment of both systolic and diastolic function.

Biomechanical Phenomena↗

The endocrine heart and natriuretic peptides: histochemistry, cell biology, and functional aspects of the renal urodilatin system.

This review focuses on some selected aspects of the endocrine heart and natriuretic peptides. The endocrine heart is composed of specific myoendocrine cells of the cardiac atria. The myoendocrine cells synthesize and secrete the natriuretic peptide hormones which exhibit natriuretic, diuretic, and vasorelaxant properties. Immunohistochemical analyses show that natriuretic peptides of the A-type and B-type are localized not only in the specific granules of these myoendocrine cells but also in many other organs including the brain, adrenal medulla, and kidney. Also, their receptors are detected in many organs showing the multiple functions of these regulatory peptides. Of the members of the natriuretic peptide family, ANP (ANP for atrial natriuretic peptide; also denominated cardiodilatin, CDD), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and the A-type, including its renal form, urodilatin, are emphasized in this review. Urodilatin is localized in the kidney, differentially processed, and secreted into the urine. The intrarenal synthesis and secretion is the basis for a paracrine system regulating water and sodium reabsorption at the level of the collecting duct. CDD/ANP-1-126, cleaved from a precursor of 126 amino acids in the heart to a 28-amino acid-containing circulating molecular form (CDD/ANP-99-126), and urodilatin (CDD/ANP-95-126) share similar biochemical features and biological functions, but urodilatin may be more involved in the regulation of body fluid volume and water-electrolyte excretion, while circulating CDD/ANP-99-126 is responsible for blood pressure regulation. The physiological and pharmacological properties of these peptides have great clinical impact, and as a consequence urodilatin is involved in drug development for the treatment of acute renal failure, cardiomyopathia, and acute asthma.

Amino Acid Sequence↗

Calcium-binding proteins in the retina of a calbindin-null mutant mouse.

Calcium-binding proteins are abundantly expressed in many neurons of mammalian retinae. Their physiological roles are, however, largely unknown. This is particularly true for calcium-modulating proteins ("calcium buffers") such as calbindin D28k. Here, we have studied retinae of wildtype (+/+) and calbindin-null mutant (-/-) mice by using immunocytochemical methods. Although calbindin immunoreactivity was completely absent in the calbindin (-/-) retinae, those cells that express the protein in wildtype retinae, such as horizontal cells, were still present and appeared normal. This was verified by immunostaining horizontal cells for various neurofilament proteins. In order to assess whether other calcium-binding proteins are upregulated in the mutant mouse and may thus compensate for the loss of calbindin, mouse retinae were also immunolabeled for parvalbumin, calretinin, and a calmodulin-like protein (CALP). In no instance could a change in the expression pattern of these proteins be detected by immunocytochemical methods. Thus, our results show that calbindin is not required for the maintenance of the light-microscopic structure of the differentiated retina and suggest roles for this protein in retinal function.

Animals↗

Urinary excretion of urodilatin in healthy children and children with renal disease.

Urodilatin (URO) is a natriuretic peptide isolated from human urine which is thought to be produced by distal tubular cells. We measured urinary URO excretion in 50 healthy children and 23 children with acute (ARF), chronic renal failure (CRF), or hereditary tubular disorders, using a specific radioimmunoassay. The mean URO excreted in these four groups was 56, 45, 94, and 121 fmol/min per 1.73 m2, respectively (differences between first three groups not significant). The variation in URO excretion was larger in patients with kidney disease than in controls. There were significant correlations between urinary URO and sodium excretion in controls and CRF, but not in ARF. URO excretion also correlated with urine flow rate in CRF. Although no correlation was found between URO excretion and creatinine clearance, urinary URO was increased in some patients with advanced CRF, which suggests stimulated tubular production to compensate for reduced sodium excretion. In view of the therapeutic potential of URO in renal insufficiency, further study of the renal handling of URO is warranted.

Acute Kidney Injury↗

Clinical research: assessing the future in a changing environment; summary report of conference sponsored by the American Medical Association Council on Scientific Affairs, Washington, DC, March 1996.

Concerns about funding of clinical research underlie all other problems identified at the Council on Scientific Affairs conference. Future National Institutes of Health (NIH) budgets are likely to be constant at best, and the general public expects cost containment to be an ongoing goal; this is exacerbated by the impending Medicare Trust Fund crisis. Meanwhile, traditional financial support of clinical research in academic medical centers (AMCs) through cross-subsidization is imperiled by competitive pressures largely caused by managed care. Although managed care organizations (MCOs) are potentially rich sources of funding and other resources, and some not-for-profit companies are conducting some research, for-profit MCOs have not demonstrated an understanding of the importance of clinical research. Young physicians are being discouraged from careers as clinical researchers and established investigators are "dropping out" because of demands for clinical productivity and competition for research grants, loss of patients/research subjects to managed care, perceived lack of status and compensation, and overall uncertainty about continued financial support. Efforts to assist current and potential clinical investigators are discussed in this report. Loss of patients, denial of reimbursement, and competition with MCOs and contract research organizations (CROs) have placed AMCs under unprecedented pressure. However, research centers located in AMCs have allowed investigators to conduct clinical research by providing a "protected environment." Furthermore, many AMCs are determined to continue conducting clinical research and are addressing related problems. Although the NIH will continue to be a major source of funding for clinical research, partnerships between various private and public entities provide important opportunities to maximize the productivity of all individuals and institutions involved. Potential partnerships include MCOs, AMCs, CROs, pharmaceutical companies and other industry, the Department of Defense, the Veterans Health Administration, practice-based physicians, and private foundations and patient support groups. "Partnerships in advocacy" for clinical research will be essential. Efforts to recruit for-profit MCOs to the clinical research endeavor identified in this report include (1) emphasizing issues of interest to them (eg, outcomes research); (2) stressing the significance of some research to the marketplace; (3) developing criteria to distinguish individual MCOs on the basis of their contribution to the public interest; (4) equating money spent on research with "R&D dollars" spent in nonmedical business enterprises; and (5) educating purchasers of health care (eg, corporate health plan directors) about clinical research. Conducting clinical research in all managed care settings requires leadership, the understanding and cooperation of physicians and support staff, wise use of limited resources (ie, funding only the best research projects), sound methodology, and above all, the perception that the research will ultimately improve patient care.

American Medical Association↗

Combined trabeculectomy and phacoemulsification: a one-site vs a two-site approach.

PURPOSE: To compare the results of combined trabeculectomy and phacoemulsification surgery with intraocular lens implant by means of a one-site vs a two-site approach. METHODS: Glaucomatous patients with a coexisting cataract were randomly assigned to undergo either a one-site or two-site combined procedure. One-site surgery was performed with a limbus-based conjunctival flap and scleral tunnel at the 12-o'clock position. Two-site surgery was performed with a limbus-based conjunctival flap for the trabeculectomy in the superior nasal quadrant and a temporal clear cornea incision for phacoemulsification. Mitomycin C (0.4 mg/ml for 2 minutes) was applied to the scleral surface at the trabeculectomy site for both approaches. All patients received intraocular lens implants at the time of combined surgery. RESULTS: Thirty-three eyes of 33 patients were included in this study. Preoperative intraocular pressure and number of glaucoma medications were similar in the two groups. Corrected visual acuity improved similarly in both groups. Intraocular pressure decreased in both groups at last follow-up but was not significantly different (P = .129) between the one-site and two-site groups. At last follow-up, the one-site group required significantly more (P = .030) medications than did the two-site group. CONCLUSIONS: Combined trabeculectomy and phacoemulsification surgery in which one-site and two-site techniques were used yielded similar improvements in corrected visual acuity and intraocular pressure reduction. However, the one-site group required more medication to maintain intraocular pressure control than did the two-site group.

Aged↗

Sarcoplasmic reticulum Ca(2+)-ATPase overexpression by adenovirus mediated gene transfer and in transgenic mice.

The sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) is a major determinant of cardiac relaxation. It has been demonstrated that the steady state levels of the mRNA coding for this pump are reduced in human heart failure due to dilated cardiomyopathy. Although results regarding the protein level are controversial, most functional studies indicate decreased SERCA2a activity in heart failure. The extent to which a potential decrease in the calcium sequestering function of this protein could contribute to the contractile dysfunction in heart failure, and whether a reconstitution of SERCA2a could alleviate heart failure, are yet unknown. To further investigate these questions two methodological approaches were chosen. Adenovirus mediated gene transfer provides an approach to study functional consequences of SERCA2a overexpression in cardiac myocytes in vitro [1], and a transgenic mouse model allows the effects of cardiac overexpression of SERCA2a to be examined in vivo [2].

Adenoviridae↗

The effect of the specific phosphodiesterase-IV-inhibitor rolipram on the ureteral peristalsis of the rabbit in vitro and in vivo.

PURPOSE: Cyclic nucleotide phosphodiesterases (PDE's) are intracellular key enzymes in the regulation of the tone in smooth muscle cells. There are 5 different isoenzyme families that show a specific organ and species distribution pattern. The aim of our study was to examine possible selective ureteral relaxation by the specific PDE-IV-inhibitor rolipram in the rabbit. MATERIALS AND METHODS: For in vitro studies ureters were taken from 12 patients who underwent radical nephrectomy and from 4 rabbits which were sacrificed. For the in vivo study 23 rabbits received intravenous administration of papaverine (300 microg./kg. b.w., n = 2), scopolamine (667 microg./kg. b.w., n = 2), theophylline (5 mg./kg. b.w., n = 2) and rolipram (5 and 20 microg./kg. b.w., n = 9 and n = 8). Ureteral dynamic parameters (frequency, amplitude, tonus) and systemic blood pressure were continuously monitored 40 minutes before and at least 60 minutes after injection of the drugs. RESULTS: Scopolamine had no effect on ureteral peristalsis, but significant effects on systemic blood pressure were observed. Papaverine and theophylline showed short-lasting ureteral relaxations, but were accompanied by severe circulatory side effects. Rolipram showed pronounced ureteral relaxation with minimal circulatory effects. CONCLUSION: Our results show that intravenous administration of the specific PDE-IV-inhibitor rolipram relaxes the rabbit ureter without significant circulatory side effects. Because human and rabbit ureter show similar relaxation results in vitro, this pharmacological approach seems promising for the treatment of ureteral colic and the facilitation of urinary stone passage in humans.

Animals↗

Nodal CT density and total tumor volume as prognostic factors after radiation therapy of stage III/IV head and neck cancer.

PURPOSE: To determine whether the immunohistochemical expression of proliferation-associated antigens (proliferating cell nuclear antigen, MIB1) and the nuclear p53 reactivity in addition to total tumor volume, nodal CT density and T and N category are predictive for overall survival and locoregional tumor control in patients with squamous cell carcinoma of the head and neck region. MATERIALS AND METHODS: Between October 1989 and September 1993, 87 patients with biopsy proven head and neck cancer were randomly allocated to receive radiation alone or simultaneous radiation and chemotherapy as part of a multicenter trial with a total of 298 randomized patients. There were only inoperable lesions in UICC (1992) stage III (8%) and IV (92%). Radiotherapy was delivered with 180 cGy twice daily up to a total dose of 7020 cGy in 51 days. Three cycles of 2340 cGy each were separated by a rest period of 11 days. Chemotherapy consisted of cis-DDP, 5-fluorouracil and leucovorin and was repeated on days 22 and 44. Routinely-processed paraffin-embedded sections were stained using monoclonal antibodies for detection of proliferation-associated antigens (MIB1 and PCNA) and p53 oncoprotein to determine the labeling index (LI). In addition, the total tumor volume and the percentage of necrosis were measured using CT data. The median follow-up was 3.9 years (range 1.9-5.0 years). RESULTS: The overall survival and locoregional control for all 87 patients were 34 and 39% at 3 years, respectively. The addition of chemotherapy resulted in a better overall survival (27 versus 47%, P = 0.03) but did not influence locoregional control (31 versus 47%, P = 0.08). In univariate analysis, nodal CT density (P < 0.0001), total tumor volume (P < 0.0001), age (P = 0.001) and the MIB1-LI (P = 0.04) had a significant impact on overall survival. However, in the final Cox model only the nodal CT density (P = 0.0003) and age (P = 0.05) were independent prognostic factors for survival and only the nodal CT density (P = 0.0006) was an independent prognostic factor for locoregional control. The expression of the p53 oncoprotein was not found to have a clear predictive value. CONCLUSION: Nodal CT density, total tumor volume and age will remain the relevant prognostic factors in stage III/IV head and neck cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Working memory constraints on syntactic ambiguity resolution as revealed by electrical brain responses.

Parsing strategies in temporarily ambiguous sentences were investigated in readers with different sentence memory capacities using event-related brain potentials (ERPs). Readers with a high memory span as well as readers with a low memory span were required to read subject and object relative sentences which were either ambiguous until the last word (late disambiguation) or were disambiguated by case marking either the clause initial pronoun (immediate disambiguation) or the noun phrase following it (early disambiguation). ERPs registered during sentence reading elicited the following effects: In the late disambiguation condition, high span readers, but not low span readers, displayed a more positive going wave at the disambiguating number marked auxiliary for the object relative sentences than for the subject relative sentences. This positivity is taken to reflect processes of revision that become necessary at the disambiguating element if the initial structure considered is a subject relative clause. When case marking was available in the clause initial at the relative pronoun, both high and low span readers showed a positivity at the disambiguating element for the object relative sentences, suggesting the immediate use of case marking information for revision. When case marking was available in the noun phrase following an ambiguous pronoun both groups showed no clear effect of revision at the disambiguating element, but only at the sentence final number marked auxiliary. This non-immediate use of the case marking information seems to be due to an inherent ambiguity in the German case marking system which interacts with the disambiguating element's position in the sentence. The combined data indicate that morphological information can be used immediately by high and low span readers to resolve syntactic ambiguity during sentence processing whenever the information given is clearly unambiguous. In addition they suggest that possible processing differences in ambiguity resolution between high and low span readers may only appear when the ambiguous regions are long.

Adult↗

Calbindin-D28k fails to protect hippocampal neurons against ischemia in spite of its cytoplasmic calcium buffering properties: evidence from calbindin-D28k knockout mice.

Cytoplasmic calcium-binding proteins are thought to shield neurons against damage induced by excessive Ca2+ elevations. Yet, in theory, a mobile cellular Ca2+ buffer could just as well promote neuronal injury by facilitating the rapid dispersion of Ca2+ throughout the cytoplasm. In sharp contrast to controls, in mice lacking the gene for calbindin-D28k, synaptic responses of hippocampal CA1 pyramidal neurons which are normally extremely vulnerable to ischemia, recovered significantly faster and more completely after a transient oxygen-glucose deprivation in vitro, and sustained less cellular damage following a 12 min carotid artery occlusion in vivo. Other cellular and synaptic properties such as the altered adaptation of action potential firing, and altered paired-pulse and frequency potentiation at affected synapses in calbindin-D28k-deficient mice were consistent with a missing intraneuronal Ca2+ buffer. Our findings provide direct experimental evidence against a neuroprotective role for calbindin-D28k.

Animals↗