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Biomedical subjects

M Holzer

Publications and source records attributed to M Holzer.

At least 73 records · Page 4Linked to original sources
PubMed1994

In vivo phosphorylation in the rat basal nucleus induces PHF-like and APP immunoreactivity.

In vivo phosphorylation was stimulated in the rat basal nucleus by stereotaxic injection of the phosphatase inhibitor okadaic acid (OA). Hyperphosphorylation of neurofilaments and of the microtubule-associated proteins tau and MAP2 was associated with their redistribution from the axonal compartment into the cell bodies of large projection neurones where they appeared as paired helical filament (PHF)-like immunoreactivity. Astrocytes showed a dramatic increase in APP immunoreactivity and changed their appearance to a stellate shape with long processes. The results demonstrate that abnormal tau phosphorylation and changes in the expression and/or metabolism of APP can be induced in vivo by altering protein phosphorylation. The present experimental paradigm might, therefore, provide a useful tool to model early steps of the pathomechanism of Alzheimer's disease.

Alzheimer Disease↗
PubMed1994

Abnormally phosphorylated tau protein in Alzheimer's disease: heterogeneity of individual regional distribution and relationship to clinical severity.

The distribution of abnormally phosphorylated tau proteins was investigated in a number of cortical areas and in the basal nucleus of Meynert of 12 patients with Alzheimer's disease. Quantification was performed with a sensitive sandwich enzyme-linked immunosorbent assay employing the monoclonal antibody B5-2, which immunoreacts with neurofibrillary tangles, dystrophic neurites surrounding amyloid cores of plaques and neuropil threads. On western blots, the monoclonal antibody B5-2 specifically labels the abnormally phosphorylated paired helical filament-tau species in a phosphorylation-dependent manner but is not cross-reactive to normal tau proteins. The preferential involvement of cytoarchitecturally defined cortical areas showed marked individual differences in Alzheimer's disease, and no unique distribution pattern of abnormally phosphorylated tau proteins could be established. While regional heterogeneities along the rostrocaudal extension of the brain declined with the progression of the disease, lateral differences which were largely non-directional appeared to be more stable over time. The mean content of abnormally phosphorylated tau proteins of individual cases was significantly related to the severity of the disease. On a regional scale, this correlation was highest for the basal nucleus. The formation of abnormally phosphorylated tau was associated with a loss of normal soluble tau proteins. Those cortical areas which in normal brain showed the highest amount of normal soluble tau proteins appeared to be particularly prone to deposition of abnormally phosphorylated tau proteins. The present results indicate that the formation of abnormally phosphorylated tau proteins can be initiated in the neuropil at more than one brain area. The spreading of the pathology appears to involve both intracortical and subcortical pathways but largely spares interhemispheric pathways. It is hypothesized that regional differences in the compartmentation and metabolism of tau proteins might reflect the molecular basis for the regionally different vulnerability in Alzheimer's disease.

Adult↗
PubMed1992

Renal haemodynamics and organ damage in young hypertensive patients with different plasma renin activities after ACE inhibition.

We describe our observations concerning differences in two groups of young hypertensive patients according to their renin activities after ACE inhibition. Seventeen of these patients (age 26 +/- 7 years), so far untreated, were investigated prospectively for hormone levels (renin, aldosterone, vasopressin), microalbuminuria, renal haemodynamics (inulin and PAH clearance) and signs of organ damage (echocardiography, fundoscopy). Secondary forms of hypertension were excluded by routine methods, including angiography. We differentiated two groups of young hypertensive patients. Group 1 (n = 9) had a false positive captopril test with elevated renin activities after ACE inhibition with captopril (8.4 +/- 5 ng/ml per hour) compared to group 2 (renin activity: 2.2 +/- 1.3 ng/ml per hour) or an increase of greater than 400% of renin activity after ACE inhibition. Baseline renin activities and sodium excretion did not differ between the groups. Group 1 also showed significantly greater GFR, FF, and microalbuminuria, as well as signs of organ damage, with left ventricular hypertrophy and hypertensive changes in fundoscopy. There were no differences between the groups concerning mean arterial blood pressure and duration of hypertension. In conclusion, we were able to demonstrate that patients with highly stimulated renin activities showed signs of visceral organ damage and renal hyperfiltration compared to the normal renin activity group after ACE inhibition. Investigations of the renin-angiotensin-aldosterone system with ACE inhibitors might constitute a helpful indicator of renal changes and organ damages in young hypertensive patients.

Adult↗
PubMed1991

Glutethimide treatment of disabling action tremor in patients with multiple sclerosis and traumatic brain injury.

Glutethimide has been used to control essential tremor. Its efficacy in the treatment of disabling cerebellar and rubral tremor was assessed in an open study of six patients with multiple sclerosis and two patients with traumatic brain injury. Functional and quantitative tremor severity was assessed before treatment and 7 to 14 days after a stable dose was achieved. Six of eight patients exhibited visible functional benefit from treatment with glutethimide; abstract testing results correlated well with functional status in most cases. Four patients chose to continue to receive medication. Controlled trials of glutethimide to compare its efficacy with that of other medications used in the treatment of action tremor are indicated.

Brain Injuries↗
PubMed1991

Hyperthermia stimulates plasminogen activator inhibitor type 1 expression in human umbilical vein endothelial cells in vitro.

The effect of exposure to hyperthermia on the fibrinolytic potential of human umbilical vein endothelial cells (HUVEC) in culture was studied. HUVEC responded to exposure to 42 degrees C with a time-dependent increase in plasminogen activator inhibitor type 1 (PAI-1) activity and antigen accompanied by a four- to fivefold increase in PAI-1 specific m-RNA and a decrease in tissue-type plasminogen activator (t-PA) antigen. The effect of 8 hours exposure to hyperthermia on PAI-1 activity and antigen could not be reversed by reexposure of the cells to 37 degrees C for 24 hours as evidenced by continuously increased amounts of PAI-1 released into the conditioned media. t-PA release, however, decreased during the 24-hour period at 37 degrees C after exposure to hyperthermia. No difference in PAI-1 antigen present in the extracellular matrix of heat treated HUVEC as compared to HUVEC kept at 37 degrees C could be found. Our data supports the idea that hyperthermia is one stress factor that influences the fibrinolytic potential of endothelial cells.

Blotting, Northern↗
PubMed1990

[Selection of HLA compatible thrombocyte donors using electronic data processing with a newly developed score].

We developed a program for personal computers which selects platelet donors for a given patient according to the following criteria: 1. Anti-CMV-status, 2. ABO-compatibility of various degrees, and 3. HLA-incompatibility. For evaluation of HLA-incompatibility, we created a score which presently provides the following classification: 0 = identical antigen, 5 = same supertypic antigen or blank in the donor, 50 = very frequently cross-reactive antigen, 75 = frequently cross-reactive antigen, very rare antigen or antigen poorly expressed on platelets in the donor, 100 = mismatch.

Blood Donors↗