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Biomedical subjects

M Meier

Publications and source records attributed to M Meier.

At least 19 recordsLinked to original sources

A continuing signal maintains NGF receptor expression in hypoglossal motor neurons after crush injury.

Inhibition of axonal transport by vincristine applied to hypoglossal nerves 7 days after crush injury turns off the usual injured-induced expression of low affinity nerve growth factor receptor (p75NGFr). Vincristine applied proximal but not distal to the crush prevents p75NGFr induction. These results indicate that a continuing signal is axonally transported from the crush site that induces and maintains p75NGFr expression by injured motor neurons.

Animals

Changes in nerve growth factor receptor-like immunoreactivity in the spinal cord after ventral funiculus lesion in adult cats.

Spinal motoneurons have a capability to regenerate CNS-type axons after intramedullary lesions in the adult cat. Regrowing axons have been traced through CNS-type scar tissue in the ventral funiculus of the spinal cord and into adjacent ventral root fascicles. This scar tissue, which appears to support and sustain regenerating axons, has been shown to have a persistent defect in the blood-brain barrier. It has been suggested that the blood-brain barrier may play a vital role in CNS regeneration by regulating the access of blood-borne trophic factors to the lesion area. In the present study, the binding of antibodies to the human nerve growth factor receptor in the cat spinal cord was examined with immunohistochemical methods 2 days to 8 weeks after a ventral funiculus lesion. The results show that, while no neurons in the ventral horn of the control material contained nerve growth factor receptor-like immunoreactivity as revealed by fluorescence microscopy, affected motoneurons expressed nerve growth factor receptor after ventral funiculus lesion. Nerve growth factor receptor-like immunoreactivity associated to both capillaries and interstitium was present in the scar tissue. Electron microscopic examination of sections labelled with the immunogold-silver method showed that perivascular nerve growth factor receptor-like immunoreactivity was located exclusively to non-pericytic perivascular cells. These cells were abundant in the expanded capillary perivascular spaces adjacent to the traumatic lesion. Similar cells, with or without relation to blood vessels, were observed in the scar tissue and in the pia mater. In a separate set of specimens it was observed that a ventral funiculus lesion combined with ventral root avulsion, which removes denervated PNS tissue, resulted in an expression of nerve growth factor receptor-like immunoreactivity which was similar to the one observed after ventral funiculus lesion only. The results of the present study show that affected motoneurons and cells in the scar tissue express nerve growth factor receptor after ventral funiculus lesion which implies that neurotrophic factors related to nerve growth factor may be of importance for the regenerative response.

Animals

Hypoglycemic effects of a beta-agonist, Ro 16-8714, in streptozotocin-diabetic rats: decreased hepatic glucose production and increased glucose utilization in oxidative muscles.

Streptozotocin (STZ)-induced diabetic rats are glycosuric, hyperglycemic, hyperketonemic, overproduce glucose, and have a decreased glucose utilization in oxidative muscles. Treatment with a beta-agonist, Ro 16-8714, decreases the glycosuria, hyperglycemia, hyperketonemia, and hepatic glucose production. Tissue glucose utilization was unchanged, except in oxidative muscles, where it was increased.

2-Hydroxyphenethylamine

Renal artery aneurysm: surgical indications and results.

The clinical course of 23 patients with 28 renal artery aneurysms (RAAs) is reported. The RAAs were recorded over a period of 10 years. Thirty-five per cent of the RAAs (eight of 23 patients) were detected during the investigation of hypertension, whereas 26% (six of 23 patients) were discovered incidentally while imaging atherosclerotic arterial disease in the aorto-iliac region by angiography. Twenty-two aneurysms were treated surgically and primary nephrectomy was necessary in one case. The surgical technique used was excision of the aneurysm with bypass grafting in 13 cases (seven Dacron, five vein, one arterial bypass), a running suture following aneurysm excision in four cases and an end-to-end anastomosis in two cases. The results (for a period of 1-10 years) were excellent in all but three cases: two early graft occlusions (vein interposition) and one late occlusion (Dacron bypass) in the course of a re-operation which had become necessary because of a ruptured aneurysm of the gastro-epiploic artery after 3 months. Three of 23 patients were treated by embolisation of four intraparenchymal aneurysms. The follow-up of a non-treated saccular aneurysm showed a total thrombosis of the aneurysm within 4 years and fixed renal hypertension developed later in this patient. We suggest surgical repair of an RAA regardless of its size and the clinical symptoms, in order to prevent microembolism into the renal parenchyma and to avoid the development of fixed renal hypertension. Intrarenal aneurysms can be treated by embolisation to stop severe haematuria thus preserving the kidney.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Involvement of the renin-angiotensin system in ischemic damage and reperfusion arrhythmias in the isolated perfused rat heart.

We have investigated the contribution of the renin-angiotensin system to the damage caused by 40-min global ischemia in the isolated rat heart. A converting enzyme inhibitor, enalaprilat (70 nM), an angiotensin II receptor antagonist, compound 89 (2 microM), and an inhibitor of rat renin, CGP 44099A (20 nM), given before ischemia reduced the median duration of ventricular fibrillation on reperfusion to a similar extent (5.53, 5.72, and 5.14 min, respectively, compared to 13.98 min in the control group) but had no effect on creatine phosphokinase release (22.2 +/- 2.6, 22.1 +/- 6.8, and 24.1 +/- 3.6, IU/30 min, respectively, compared to 19.9 +/- 1.9 IU/30 min) or recovery or left ventricular developed pressure (67 +/- 6, 73 +/- 7 and 71 +/- 6%, respectively, compared to 66 +/- 3% after 30 min reperfusion). The increase in coronary resistance and left ventricular diastolic pressure on reperfusion was not affected by any of the agents. All three agents also tended to reduce the duration of ventricular fibrillation when given only on reperfusion. We conclude that angiotensinogen is present in the rat heart and it is converted to angiotensin I by a renin or a renin-like aspartic proteinase. The angiotensin I is converted to angiotensin II by converting enzyme. The angiotensin II formed is an important mediator of postreperfusion ventricular fibrillation in the isolated rat heart but does not contribute to the reduction in mechanical function produced by global ischemia in this preparation.

Animals

Follicular mucinosis associated with mycosis fungoides.

We report a patient who developed erythematous indurated plaques with alopecia on the face and multiple well-demarcated infiltrated scaling lesions on the trunk and extremities. Skin biopsy showed a mucinous degeneration of the follicular outer root sheaths and sebaceous glands consistent with the diagnosis of follicular mucinosis. A histologic examination of a specimen from the left forearm showed microscopic changes of mycosis fungoides. The present case confirms the need of multiple skin biopsies in the evaluation of patients with follicular mucinosis.

Aged

[Determination of beta-N-acetylglucosaminidase and albumin in urine: comparison of methods and effect of gel filtration in human and rat urine].

A new kinetic method for determination of beta-N-acetylglucosaminidase (beta-NAG, EC 3.2.1.30) in human and rat urine with chlorophenol red-NAG as substrate is compared to two other methods with 4-nitrophenyl-NAG and 3-cresol-sulfonphthaleinyl-NAG respectively as substrates. The impact of gel filtration of urinary specimens on the determination of beta-NAG-activity and of low albumin concentrations in urine is described.

Acetylglucosaminidase

Cloning of a gene that encodes a new member of the human cytotoxic cell protease family.

A family of unusual serine proteases that are believed to be involved in the effector mechanism of cell-mediated cytotoxicity have previously been described in the mouse. However, in the human only one gene encoding a member has been isolated. By use of a mixture of murine cDNAs as probes, a second human gene has now been isolated. The primary structures of the gene and the predicted protein are very similar to those of the mouse. In addition, in keeping with the postulated involvement in cytolysis, transcripts were detected only in cytotoxic cells. The organization of the coding and noncoding regions of the gene, the clustering of family members, and the chromosomal location, close to the alpha chain of the T cell antigen receptor, are all conserved between human and mouse.

Amino Acid Sequence

Teratogenic effect of the cholesterol synthesis inhibitor AY 9944 on rat embryos in vitro.

AY 9944 [trans-1,4-bis(2-chlorobenzylaminomethyl) cyclohexane dihydrochloride] is an amphiphilic cationic molecule. This chemical is an established inhibitor of cholesterol synthesis and is teratogenic in rats. The mechanisms of this teratogenicity remain to be clarified. This study used cultured rat whole embryos to ascertain whether AY 9944 had a direct effect on embryos, or whether its action was indirect, via the maternal cholesterol metabolism. Four experimental conditions were investigated: (A) controls; (B) 10 day untreated embryos were cultured in serum of treated rats; (C) 10 day untreated embryos were cultured in serum containing added AY 9944 (0-1,000 micrograms/ml); and (D) 10 day embryos from females treated on day 4 of gestation were cultured in normal serum. In group B there was no growth retardation; some slight nonspecific abnormalities were not significant. In group C, direct addition of AY 9944 to culture medium retarded growth and differentiation in a dose-dependent manner. No malformation was observed, but histological examinations showed numerous areas of cell necrosis, especially in the CNS. In group D, not only was growth retardation observed, but also characteristic malformations of AY 9944 teratogenesis, including pituitary agenesis. These results show that AY 9944 teratogenicity is initiated prior to day 10.

Abnormalities, Drug-Induced

Hepatic encephalopathy influences high-affinity uptake of transmitter glutamate and aspartate into the hippocampal formation.

The present work was carried out to study the influence of ammonia and factors from sera and cerebrospinal fluid (CSF) from patients with different degrees of chronic liver diseases on [3H]D-aspartate (Asp) and [3H]L-glutamate (Glu) high-affinity uptake into the rat hippocampal formation. For comparison, high-affinity uptake of Glu and Asp was determined in human hippocampal brain tissue obtained at autopsy from cirrhotic patients dying in hepatic coma and from control brains free from neurological, psychiatric, or hepatic diseases. Sera and CSF from patients with chronic liver failure and hepatic encephalopathy (HE) were seen to reduce dramatically Glu and Asp uptake into rat hippocampal dendritic layers. A close inverse relationship was found to exist between the level of ammonia in the sera and the inhibition of uptake, both phenomena correlating highly with the extent of liver failure. The present findings, obtained after dilution of sera from patients with HE while maintaining initial ammonium levels, elucidate, however, that ammonia alone cannot account for the reduction in Glu/Asp uptake capacity. The inhibition of Asp uptake into human hippocampal formation of patients dying in hepatic coma was even more pronounced when compared to that found in rat hippocampus incubated in sera and CSF from patients. Glu/Asp uptake into brain tissue is supposed to be an important factor in the pathogenesis of HE accompanying liver dysfunctions.

Adult

Mercury and copper release from amalgams in different soft drinks.

Release of mercury and copper over time from three different non-gamma-2 amalgams in a polished and unpolished state was tested in water and two soft drinks. The measuring methodology was geared to warrant minimum Hg losses due to evaporation and adsorption. Initial (24 h) values for Hg and Cu were relatively high in water, but were much lower in the soft drinks. The 24-104-hour values were much lower than the initial readings for all amalgams and all environments. Polishing reduced leaching--significantly, however, only in water and for only two of the three amalgams. The lower values in the soft drinks and over time could be due to passivation of the amalgam. Passivation appears to be time-dependent and chemically influenced by the environment.

Carbonated Beverages

Chromosome localization of two human serine protease genes to region 14q11.2----q12 by in situ hybridization.

Two human serine protease genes have been cloned. One corresponds to CTLA1, the human equivalent of the mouse cytotoxic cell protease gene Ctla-1, and the other is novel. Both genes were localized to 14q11.2----q12 by in situ hybridization. This result confirms the assignment of human CTLA1 to 14q11.2----q12 and provides new mapping data for another human serine protease gene located in the same chromosome region.

Chromosome Mapping

Transcriptional regulation of two cytotoxic T lymphocyte-specific serine protease genes.

The expression of two serine proteases is induced by antigenic stimulation in cytotoxic T lymphocytes. Using nuclear run-on analysis the increase in steady state mRNA level has been shown to correspond to transcriptional activation. However, the two genes appear to be sequentially rather than coordinately induced. Both genes were shown to be more sensitive to DNase I digestion than a beta-globin gene in cytotoxic T cells. In addition, for the cytotoxic cell protease 1 gene the 5' region of the gene was more sensitive than the 3' end. Two DNaseI hypersensitive sites were seen in the 5' flanking sequences of both genes. The DNA sequences of the upstream regions of both genes were determined and compared. Although the two flanking sequences are overall quite dissimilar, there are short regions which are shared between the two CTL-protease genes. A number of these have been implicated in regulating the expression of other T cell genes.

Animals

Human placental microvilli as a source of antigen for the preparation of a polyclonal antibody directed against the LDL receptor.

Polyclonal antibodies were prepared by immunization of rabbits with partially purified LDL receptor obtained from human placental microvilli. The antiserum reacted with membranes from human placental microvilli and human fibroblasts, as assessed by immunobinding studies. It also reacted with purified LDL receptors of both origins. The antiserum markedly inhibited 125I-labeled LDL binding to cultured human fibroblasts.

Antibody Formation

The impact of splenectomy on antibody response in the porcine model.

Some controversy exists regarding the antibody response after splenectomy and spleen preserving operations. In a porcine model the specific IgG antibody response to tetanus toxoid and type 6B pneumococcal polysaccharide was studied in 10 animals with splenectomy, 11 animals with splenic resection, 10 animals with splenic autotransplantation and 10 sham operated control animals. The operative groups were divided in two subgroups, receiving either the immuno adjuvant MTP-PE or the vehicle alone. Specific antibodies were determined by ELISA. Immunization with tetanus toxoid led to slightly lower peak IgG levels in splenectomized animals, but this was statistically not significant as compared to controls. In addition, the distribution of responders (78%) was not influenced by type of operation. Type 6B-pneumococcal polysaccharide proved to be a weak immunogen (19% responders). Splenectomy or spleen preserving surgery had no impact on the proportion of responders and peak IgG antibody titers of responders to this antigen. Additional administration of MTP-PE did not significantly increase the proportion of responders and had no impact on peak IgG antibody levels to tetanus toxoid and type 6B pneumococcal polysaccharide. These results show in contrast to previous studies in man, that under controlled conditions in the porcine model serum antibody responses to T-cell dependent and T-cell independent antigens are only slightly decreased by splenectomy. In addition, no effects of spleen preserving operations on antibody response are observed, and there is no change after concomitant administration of a muramyl peptide.

Acetylmuramyl-Alanyl-Isoglutamine

Apoprotein AII in acute pancreatitis: intriguing improvement in the prediction of fatal outcome.

In spite of significant advances in the past decade, assessing of severe prognosis in acute pancreatitis remains an improvable problem. Actually the standardized means are clinical, multiple laboratory and peritoneal lavage. In a series of 20 subsequent cases of acute pancreatitis with a lethality of 30%, apolipoprotein AII has proven to be a predictor of fatal outcome with a sensitivity in the range of all other methods together. Competitive replacement of Apo AII by serum amyloid like substance A as an indicator for the amount of necrosis would explain this relation. Whether this suggestion can be confirmed by ongoing work or not, apolipoprotein AII merits attention in this context.

Acute Disease