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Biomedical subjects

V Meininger

Publications and source records attributed to V Meininger.

At least 37 records · Page 2Linked to original sources
PubMed1991

Comparative anatomy and histology of the radial artery and the internal thoracic artery. Implication for coronary artery bypass.

Anatomical characteristics of the radial a. were compared to those of the internal thoracic a., considered as a gold standard in coronary surgery. The length, the diameter, the collateral distribution and the wall thickness of these two arteries were studied comparatively. In addition, a comparative histological analysis was carried out. Anatomical and histological characteristics of these two arteries have important implications for coronary artery bypass.

Angiography↗
PubMed1991

Quantitative analysis of monoclonal immunoglobulins in serum of patients with amyotrophic lateral sclerosis.

In a prospective study, we analysed the presence of monoclonal immunoglobulin (moIg) in the serum from 30 patients with amyotrophic lateral sclerosis (ALS) and 30 matched controls using a sensitive Western blot technique. The incidence of serum moIg was 60% in the ALS group and 13.3% in the control group. Most ALS sera contained 2 or 3 monoclonal components. They were IgG (72.7%) and IgM (27.3%). These results corroborate the concept of a probable association between ALS and serum moIg.

Adolescent↗
PubMed1991

[Role of percutaneous endoscopic gastrostomy in amyotrophic lateral sclerosis].

Percutaneous endoscopic gastrostomy (PEG) is an enteral nutritional assistance technique using a simple device compatible with conventional feeding and thus enabling the patient to be integrated into his or her social and familial surroundings. This inexpensive device is quickly and easily inserted under local anaesthesia. It causes little morbidity and virtually no mortality and has many advantages for patients with amyotrophic lateral sclerosis (ALS). We report the results of PEG in 28 ALS patients with bulbar involvement. Three of these patients developed minor complications during 6 consecutive months of PEG-assisted nutrition (2 had periostomial infection, 1 had mild haematemesis). There were no major complications, and mortality directly ascribable to PEG was nil. All patients put on weight or had their weight stabilized, and GEP was well accepted in all cases.

Adult↗
PubMed1990

Immunofluorescence study of the action of navelbine, vincristine and vinblastine on mitotic and axonal microtubules.

Among the various non-naturally-occurring Vinca alkaloid compounds, nor-anhydro-vinblastine (Navelbine, NVB) exhibits in preliminary clinical studies broader anti-tumor activity and lower neurotoxicity than vinblastine (VBL) and vincristine (VCR). The action of these 3 Vinca alkaloids on axonal and mitotic microtubules has been studied experimentally in a specific model, the tectal plate anlage of mouse embryos at the earliest stages of neuronal differentiation. Post-implantation embryos were cultured in toto in a medium containing increasing concentrations of drugs. Microtubules were stained using immunofluorescence with a tubulin-specific polyclonal antibody in semi-thin sections after embedding in high-molecular-weight polyethylene glycol. All drugs induced depolymerization of mitotic interpolar microtubules and cell metaphase block at the same concentration. Increasing the concentrations led to progressive depolymerization of kinetochore microtubules. However, NVB was the only drug to induce complete microtubule depolymerization. The activity of the 3 compounds on axonal microtubules was identical: depolymerization of a labile pool of microtubules. This was observed at higher concentrations with NVB than with the 2 other Vinca alkaloids. Our results show that, in this model, NVB is as active on mitotic microtubules as VCR and VBL, and less active on axonal microtubules. None of the 3 drugs modified microtubule length but all appeared to induce disruption of the labile microtubule pool without altering the stable pool.

Animals↗
PubMed1990

Embryotoxic effects of sodium arsenite and sodium arsenate on mouse embryos in culture.

Embryotoxic effects of two inorganic arsenic compounds, sodium arsenite (Asi) and sodium arsenate (Asa), on the development of mouse embryos during early organogenesis were studied using the whole embryo culture technique. Embryos with three to five somites exposed to 1-40 microM Asi or to 10-400 microM Asa were cultured for 48 hours and their development was compared with that of control embryos. Asi proved to be teratogenic between 3 and 4 microM and embryolethal at higher concentrations; Asa had similar activity but at concentrations ten times higher than for Asi. Both compounds produced a growth retardation and a similar pattern of defects. Growth retardation was indicated by a statistically significant reduction in crown-rump length, head length, and yolk sac diameter. Abnormal embryos were characterized by hypoplasia of the prosencephalon with open neural tube, hydropericardium, somite abnormalities, and failure of development of limb buds and sensory placodes. These results confirm that both Asa and Asi are embryotoxic compounds and that the Asi activity occurs at concentrations ten times lower than for Asa. Our results suggest that in humans both of these compounds may be involved in part of "unaccountable" early abortions and malformations claimed to be due to the toxicity of heavy metals.

Animals↗
PubMed1990

In situ response to vinka alkaloids by microtubules in cultured post-implanted mouse embryos.

The response of microtubules to treatment with vinca alkaloids was investigated in vivo and in situ in the embryonic nervous system of mice. For this purpose we used rotatory cultures of post-implanted embryos in a serum medium containing the alkaloid combined with immunofluorescence using a tubulin-specific polyclonal antibody on high molecular weight polyethylene glycol embedded semithin sections. In mitotic cells, kinetochore microtubules were seen to be more resistant to the action of vinca alkaloids than interpolar microtubules. Increasing drug concentrations induced an increasing rate of mitosis together with an increasing rate of disassembly of the cytoplasmic microtubule complex, suggesting a probable relation between these events. In bipolar neuroepithelial cells at interphase, a small pool of microtubules was resistant to the vinca alkaloids. These microtubules were located near the centriolar apparatus associated with the primary cilium; they were short, curly and bent. Disruption of the cytoplasmic microtubule complex did not alter the shape of the bipolar neuroepithelial cells. In the axonal profiles, a drug-stable pool of microtubules were not disrupted by the alkaloids and were also short. They seem to act as microtubule organizing centres. These observations suggest vinca alkaloids seem to act in vivo much more by inducing, at a given concentration, the disruption of a particular group of microtubules without altering the others. The fact that these drugs affect the number, but not the length, of the microtubules raises the hypothesis that these drugs act on microtubules by a mechanism similar to that described as "dynamic instability".

Animals↗
PubMed1989

Dynamics of the junction between the medulla and the cervical spinal cord: an in vivo study in the sagittal plane by magnetic resonance imaging.

Sagittal sections of the brain-stem made by MRI reveal differences in the angle formed by the medulla and the cord. In order to study the normal mobility of this region of the CNS during flexion and extension of the head, sagittal MRI studies were made in the sagittal plane in 18 young volunteers. The volunteers were in dorsal decubitus with the cervical spine first flexed and then extended, with the movement localized to the cranio-cervical junction as far as possible. T1-weighted sequences were used, with body coils in 16 cases and surface coils in two. Measurements were related to global cranio-cervical range of movement, movement at the cranio-cervical junction and spino-medullary movement. Variations in the depth of the free space in front of the medulla, pons and spinal cord during movement were also noted. We also checked for downward shift of the lower part of the 4th ventricle and modification of the shape of the ventricle during flexion-extension. The global range of cranio-cervical movement was between 31 and 100 degrees (average 63 degrees). The range between the cranium and C1C2 was 4 to 39 degrees (average 19 degrees) and the spino-medullary range was from 1 to 32 degrees (average 14 degrees). During flexion, the free space narrowed in front of the pons 11 times, in front of the medulla 14 times and in front of the cervical cord 11 times. There was a downward shift of the lower part of the 4th ventricle during flexion in 4 cases but no change in shape was noted. Though this study is open to criticism from several aspects, it may be concluded that variations of the spino-medullary angle in the sagittal plane during flexion-extension do occur, that they are closely correlated with movements at the cranio-cervical junction, moves forward during flexion.

Adult↗
PubMed1989

Characteristics of microtubules at the different stages of neuronal differentiation and maturation.

The developing nervous system has proved to be a very powerful tool to analyze how MT are involved in basic biological processes such as cell proliferation, cell migration, cell shaping, and transport. A better knowledge of the basic events occurring during neurogenesis also affords us the possibility of establishing the basis of experiments and trying to solve unanswered and important questions. Despite the considerable value of cell culture, we need to use more discrete regions of the developing brain in situ in order to analyze the MT and their modifications into cells developing their "natural" environment. One major problem remains the question of the mode of assembly and disassembly, that is, the behavior of MT in living cells. Dynamic instability and/or treadmilling are accurate interpretations of the dynamics of MT at least in vitro or in cell culture, but we do need more information on what happens in situ and in vitro. One of the main tasks of cell biologists is to devise satisfactory tests to approach this fundamental question. In this view, pharmacological manipulation of embryos treated in whole-embryo culture systems might be a possible way. Microtubules are ubiquitous cell components. However, the extensive heterogeneity of MAP and tubulin in the CNS confers on the neurons a wide range of capabilities of assembly of these proteins and suggests that the neuron has a unique potential of a relation between MT composition and cell function. We have seen that each major event during neurogenesis is related to a specific series of modifications of the MT components. It remains to be determined if there is a causal or just a correlative relationship between the appearance of specific isotypes and the occurrence of specific events and/or functions. We have also to determine the exact spatial and temporal relations among the different isotypes of MT proteins, tubulin, and MAP. Is there a close correspondence between a tubulin and a MAP isotype? Can the appearance of one isotype of tubulin influence the appearance and the assembly of a specific MAP, or vice versa? Recent results obtained with the Tyr- and Glu-MT shed light on these questions and suggest a whole series of possibilities for cells to modulate the structure, behavior, and function of MT in specific domains of the neuron or in specific regions of the brain, by only a minute modification of the molecule of tubulin. Microtubule protein heterogeneity raises also a number of questions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1989

[Management of amyotrophic lateral sclerosis].

There is no specific treatment for patients with amyotrophic lateral sclerosis. Nevertheless several associations of patients have been created to stimulate the research to find the causes and treatments of the disease and to help the patients. In spite of the absence of a specific treatment, new symptomatic therapeutic resources have been recently introduced in order to modify the management and in some cases to improve the condition of patients with ALS. Among these resources, it is worth outlining those which are devoted to the medulla trouble such as the permanent gastric tubes. The respiratory insufficiency is an early phenomenon and is considered the main prognostic factor. Its management should become soon one of the main therapeutic targets. In some countries the indications of devices for respiratory assistance at home are not rare. It is not impossible that in a near future we shall propose such devices to our patients. Beside these therapeutic resources which are difficult to manage, there are numerous drugs used to improve spasticity, cramps or drooling. Physiotherapy and speech therapy are of great importance. The management of such patients needs the cooperation of all the medical and paramedical members and the family whose role is essential.

Amyotrophic Lateral Sclerosis↗
PubMed1989

Biochemical effects of Navelbine on tubulin and associated proteins.

Navelbine (NVB) or 5' nor-anhydro-vinblastine was shown to present a broader antitumor activity and to induce fewer side effects than vinblastine (VBL) or vincristine (VCR). The possible mechanisms of these differences were analyzed with in vitro methods. At substoichiometric concentrations, the three drugs inhibit microtubule assembly. NVB, in comparison with VCR and VBL, is shown to have a lower inhibitory effect. At stoichiometric concentrations, the three drugs are able to induce tubulin aggregation into spirals and paracrystals. This process involves a microtubule-associated protein (MAPs) family referred to as Tau and is inhibited by another MAPs family referred to as MAP2. However, dramatic quantitative and qualitative differences are observed between NVB and VLB or VCR in TAU-induced aggregation of tubulin. The rate and extent of NVB-induced tubulin aggregation is much lower. With NVB, only certain TAU isoforms are able to induce paracrystals, while all TAU isoforms may contribute to VCR-induced or VBL-induced paracrystals. The TAU isoforms that are not able to induce crystallization with NVB, at least in a certain range of concentrations, are probably involved in mitotic microtubules--the hypothetical antitumoral target of vinca alkaloids (VAS). The present work shows for the first time that an anticancer drug is able to discriminate between the various types of microtubules. A next step will be to investigate whether this property is limited to a modulating effect of the various TAU isoforms on the affinity of VAS for tubulin. These biochemical investigations will be extended to tubulins extracted from tumor cell lines in order to further discriminate NVB from the other VAS.

Animals↗
PubMed1989

In situ analysis of the action of Navelbine on various types of microtubules using immunofluorescence.

Preliminary clinical studies demonstrated that 5' nor-anhydro-vinblastine, Navelbine (NVB) has a broader antitumor activity and fewer neurotoxic effects than vinblastine or vincristine. The tectal plate anlage of mouse embryos at the earliest stages of neuronal differentiation were used to analyze and compare the effect of NVB, vincristine and vinblastine on axonal and mitotic microtubules after culture of post-implantation embryos in a medium containing the agent. All drugs are active on mitotic microtubules at the same concentration (0.1 mumol/L), inducing a depolymerization of microtubules and a blockade of cells at metaphase. At higher concentrations. NVB is the only one of the three drugs that induces a blockade of the cells at prophase. A depolymerization of axonal microtubules occurs at higher concentrations with NVB than with the two other vinca alkaloids. These results demonstrate that NVB is as active on mitotic microtubules and less active on axonal microtubules than vincristine and vinblastine. These findings can be related to the potent antitumor effect of the drug with minor neurotoxicity.

Animals↗
PubMed1988

Biochemical basis of microtubule cold stability in the peripheral and central nervous systems.

Cold-stable, cold-labile and unpolymerized tubulins extracted from thalamic nuclei (soma-enriched fraction) and various nerves (both central and peripheral: axon-enriched fractions) appear different when analyzed by high-resolution isoelectric focusing. Cold-labile tubulin appears identical to unpolymerized tubulin. The axonal fractions contain fewer tubulin isotypes than the soma-enriched fraction; the peripheral axonal fraction has fewer isotypes than the central fraction. Cold-stable tubulin exhibits a specific pattern characterized by the abundance of two isotypes of alpha-tubulin, 7 and 8, and one beta-tubulin, isotype 9, with slightly different patterns of the axon-enriched fractions from the central and peripheral nervous systems. Our results suggest that the cold stability of microtubules is based on biochemical properties of tubulin, and confirm the domain specificity of the heterogeneity of tubulin.

Animals↗
PubMed1988

Modifications of tubulin heterogeneity during axonal growth in the embryonic nervous system.

Tectal plates of mouse embryos were used to analyze the heterogeneity of tubulin with high resolution isoelectric focusing, at time of appearance of the young neurons and axons. In the cold-labile pool of tubulin, isotypes 6 and 7 appear, and isotypes 1, 3, 11, 13 increase their relative quantities. The increase of the prominence of the alpha-group with regard to the beta-group in the cold-stable pool of tubulin raises the question as to the exact role of tubulin in the cold stability. A role of other specific microtubule components also appears probable.

Animals↗
PubMed1988

Spatial organization of microtubules in various types of cells in the embryonic tectal plate of mouse using immunofluorescence after PEG embedding.

The spatial organization of microtubules in mitotic as well as in interphase cells and in axons has been investigated in situ in the embryonic nervous system of mice using high molecular weight polyethylene glycol-embedded semithin sections and immunofluorescence with a tubulin-specific polyclonal antibody. In situ, the overall process of mitosis appears nearly identical to that described in cell culture. All types of mitotic microtubules (kinetochore, interpolar and asterial) can be visualized at the different stages. The slight differences from observations in cell culture are explained by differences in cell interactions. In bipolar neuroepithelial cells, interphasic microtubules appear in the form of a framework surrounding the nucleus during its to-and-fro movements and which follows the modifications in shape of the cell processes. These microtubules seem to play an active role in the mechanism, indicating the modifications in length of the apical process. In the differentiating young neuron, tubulin increases in amount to be involved in the elongation of axonal microtubules. This increase seems to be independent of the presence of axons in the environment. Axonal microtubules are independent of a microtubule-organizing center localized in the perikaryon.

Animals↗
PubMed1988

Modifications of microtubule proteins in ALS nerve precede detectable histologic and ultrastructural changes.

Fast axonal transport is altered in nerves from amyotrophic lateral sclerosis (ALS) patients. Microtubules are involved in axonal transport. We analyzed the possibility of an involvement of microtubule modifications underlying the alterations in transport using biochemical and morphologic analysis of intercostal nerves from ALS and control patients. In intercostal nerves displaying no morphologic signs of acute neuronal degeneration, two-dimensional gels showed modifications of the group of beta tubulins and abnormal spots of proteins, some appearing to be closely related to tau proteins. These results suggest that microtubule proteins are modified in ALS before ultrastructural axonal degeneration, but the significance of these abnormalities remains hypothetical.

Adult↗
PubMed1988

[Biochemical and immunocytochemical study of the axonal domain of mature and immature microtubules].

The axonal domain of microtubules was analyzed using biochemistry and immunocytochemistry. High resolution isofocusing was used to study the cold-labile and cold-stable fractions of various samples: thalamus, optic nerve, sciatic nerve, brachial plexus and trigeminal nerve. The cold-labile fraction from the thalamus, i.e. from a central nervous system cell population contains 20 well-resolved isotypes as the axonal fraction from the central nervous system. The cold-stable fraction from the peripheral nervous system contains only 18 isotypes. All the cold-stable fractions are characterized by an important relative quantity of isotypes 7-9, with specific patterns tissue dependent. The cold-labile fractions are specific in both the central and peripheral nervous system. Immunocytochemistry using anti-tubulin and anti-MAP2 specific antibodies was used in PEG semi-thin sections of the embryonic tectal plate at stage E10. In the axonal profiles, cold-stable fragments of microtubules were observed. The perikaryon of the young neurons, both migrating and post-migratory, contains MAP2 as the cold-labile fractions of microtubules of the axonal process. These results suggest that; tubulin is involved in the cold-stability of the axonal domain, but this role seems tissue dependent; MAP2 is a marker of neuronal differentiation; in the growing axonal process, cold-stable fragments are present and the cold-labile pool of microtubules contain a transiently expressed protein, MAP2.

Animals↗