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Biomedical subjects

M Novak

Publications and source records attributed to M Novak.

At least 37 records · Page 2Linked to original sources

Effects of cyclophosphamide and dexamethasone on mast cell populations in Hymenolepis microstoma-infected mice.

Antineoplastic cyclophosphamide (CY) significantly reduced the survival and the weight of Hymenolepis microstoma in mice. Corticosteroid dexamethasone (DEX), on the other hand, did not influence the worm survival and the worms in DEX-treated mice became significantly heavier. Both immunosuppressants abolished H. microstoma-induced bile duct hypertrophy and submucous enteritis and lowered the number of mast cells (MC) in these regions. CY appeared to be more effective in depleting the bile duct MC whereas DEX seemed to affect more the duodenal MC population.

Analysis of Variance

Carnitine supplementation in soy-based formula-fed infants.

Gradual increase of carnitine in plasma, tissues and urine after birth is a normal response of breast-fed infants and those receiving carnitine-containing formulas. Marked reduction of carnitine and acylcarnitines was noted in infants given diets not containing carnitine. These differences prompted the evaluation of the rationale for adding carnitine into soy-based formulas. In healthy term infants the lack of dietary carnitine did not induce deficiency symptoms but reduced the uptake of fatty acids for beta-oxidation. The cumulative effect of various metabolic disorders and carnitine deficient diets may culminate to carnitine deficiency.

Carnitine

Molecular analysis of neurofibrillary degeneration in Alzheimer's disease. An immunohistochemical study.

Antibodies directed against three regions of tau, ubiquitin, and B-amyloid were used in a histologic study of neurofibrillary degeneration in Alzheimer's disease to distinguish two populations of neurofibrillary tangles. Intracellular tangles were immunolabeled exclusively by two antibodies raised against antigens in the fuzzy coat of the paired helical filament (PHF). Extracellular tangles were distinguished by selective immunolabeling with a monoclonal antibody raised against antigens in the PHF core. This was associated with removal of the fuzzy coat and exposure of PHF-core epitopes. In the transition from intracellular to extracellular compartments in vivo, tangles appeared to undergo changes similar to protease digestion in vitro. The transition was associated with the appearance of amyloid immunoreactivity. These findings suggest that tangle degradation occurs in a series of distinct stages, including ubiquitination of some unknown molecule, a change in tau immunoreactivity, and partial proteolysis of tangle-bound tau in extracellular tangles.

Aged

H and 13C n.m.r. studies of serum from normal and Echinococcus multilocularis infected jirds.

The major components of the 13C and high field region of the 1H nuclear magnetic resonance (n.m.r.) spectra of normal and Echinococcus multilocularis infected jirds were identified and compared. Substantial depletion of the glucose and fatty acid chains from lower density lipoproteins was detected in sera from infected animals. In addition, this proliferating metacestode markedly changed the appearance of the spectral region recently assigned to N-acetyl protons of carbohydrate side chains of N-acetylated glycoproteins.

Animals

Application of a multidimensional caregiver burden inventory.

Multidimensional measures of caregiver burden give a sensitive reading of caregivers' feelings and a sophisticated picture of caregivers' responses to the demands of care. This paper reports on the development of a 24-item, five-subscale Caregiver Burden Inventory (CBI) and demonstrates its use as a diagnostic tool for professional caregivers. It concludes with a discussion of several ways that professional caregivers can use this multidimensional measure of caregiver burden.

Alzheimer Disease

Caregiver response to Alzheimer's disease.

Research on Alzheimer's Disease caregivers has tried to find a link between 1) the length of time a caregiver has been giving care; or 2) the physical condition of the patient and the experiences and needs of the caregiver. This study found no significant correlation between length of time a caregiver had given care to a particular patient and the caregiver's subjective feelings of caregiver burden. It found a significant, moderate correlation between caregiver burden and the patient's functional ability. It found that caregivers' subjective feelings and needs best predict their feelings of burden. This report concludes with suggestions on how to improve support for caregivers in light of these findings.

Aged

Surgical approach to upper basilar trunk aneurysms: a case report.

The authors report on a double aneurysm of the basilar artery (BA), located at the basilar artery bifurcation and upper basilar-artery trunk Between the posterior cerebral artery (PCA) and superior cerebellar artery (SCA). The clinical presentation, neuroradiological findings, surgical approach and operative technique are described and discussed.

Aneurysm

Characterisation of the first monoclonal antibody against the pronase resistant core of the Alzheimer PHF.

A monoclonal antibody, NOAL 6.423 has been produced which unequivocally identifies a protein which is a constituent of the pronase resistant core of the Alzheimer PHF. Although the site recognised by this antibody is contained somewhere within the highly conserved triple repeat region of the tau molecule, no experiments have succeeded so far in demonstrating NOAL 6.423 reactivity in any brain proteins other than those derived from PHFs. A site which can be recognised by NOAL 6.423 cannot be generated in preparations of normal porcine tau by simple proteolytic cleavage with pronase. Likewise reactivity with the PHF peptide recognised by NOAL 6.423 is not altered by alkaline phosphatase. The unusual properties of NOAL 6.423 are consistent with the possibility that its recognition site is not determined solely by the primary structure of the conserved region of the tau molecule.

Alzheimer Disease

[Root canal measurement].

We have analysed the filling length in 495 teeth, the length of which was measured with various methods routinously used in practice today. Significantly better fillings of root canals after pulpectomy were observed in the group, in which the length of canals was measured with odontometer, in comparison with the group, in which the lengths were measured with the tactile sense method (P less than 0.01), and with the group, in which the length was measured with preoperative radiogram only (P less than 0.05). The odontometric method resulted in statistically significant reduction of overfilled teeth in comparison with the x-ray measurement and with the radiogram made with the instrument in the root canal (P less than 0.01).

Dental Pulp Cavity

Effect of dialysate composition on the lipid response to L-carnitine supplementation.

Cumulative carnitine losses through dialysis membranes may worsen hyperlipidemia during long-term hemodialysis. However, carnitine supplementation has not shown a consistent beneficial response in hyperlipidemia. We have compared in a double-blind, cross-over study the effect of dialysate buffer composition (acetate or bicarbonate) on the serum lipid response to L-carnitine supplementation during hemodialysis. We studied nine patients (mean age, 19 years; range, 14 to 23) with hyperlipidemia undergoing maintenance hemodialysis. Plasma levels of carnitines and lipids, including total and HDL cholesterol (HDL-C) and triglycerides (TG), were measured at baseline and monthly intervals after receiving 2 grams of L-carnitine or placebo added to dialysis bath for three months. One month of carnitine supplementation in acetate hemodialysis significantly reduced plasma TG (230 +/- 95 to 136 +/- 20 mg/dl; P less than 0.05) and elevated HDL-C (50 +/- 12 to 71 +/- 26 mg/dl; P less than 0.05). However, this effect was no longer observed at the end of three months of supplementation. Bicarbonate hemodialysis had lower baseline TG values, but carnitine supplementation did not modify plasma lipids (TG:144 +/- 87 to 158 +/- 115 mg/dl; HDL-C:50 +/- 23 to 50 +/- 19 mg/dl). Both groups had a significant increase in plasma carnitine levels after carnitine supplementation. These results suggest that bicarbonate hemodialysis may add a protective effect in hyperlipidemia by reducing requirements of carnitine supplementation. On the other hand, carnitine supplementation should be considered in patients with hyperlipidemia undergoing acetate hemodialysis. The observed difference in response between acetate and bicarbonate hemodialysis may be due to enhanced formation of acetyl-CoA and fatty acid synthesis during acetate hemodialysis.

Acetates

Isolation of a fragment of tau derived from the core of the paired helical filament of Alzheimer disease.

A substantially enriched preparation of Alzheimer paired helical filaments (PHFs) has been used as a starting point for biochemical studies. Pronase treatment, which strips off adhering proteins, leaves a resistant core that is structurally intact. This has been used to raise a monoclonal antibody that decorates the filament core. The antibody has been used to follow the extraction of two peptide fragments (9.5 and 12 kDa) by immunoblotting. The link between the PHF as a morphological entity and these peptides has been established independently by photoaffinity labeling with a chemical ligand to the PHF core. Sequence analysis of these peptides was used to design oligonucleotide probes for cloning a cognate cDNA, which leads to its identification as human microtubule-associated tau protein. The sequencing of the 9.5- and 12-kDa peptides shows they are derived from a conserved region of tau containing three repeating segments. Since these fragments have been copurified with the Pronase-resistant core and are only released by subsequent steps, the corresponding part of the tau molecule must be tightly bound in the PHF core.

Alzheimer Disease

Structural characterization of the core of the paired helical filament of Alzheimer disease.

The paired helical filament, the principal constituent of the neurofibrillary tangles characteristic of Alzheimer disease, is shown to consist of two structurally distinct parts. An external fuzzy region can be removed by Pronase treatment to leave a Pronase-resistant morphologically recognizable core. Scanning transmission electron microscopy gives an estimate for the mass per unit length as 79 kDa.nm-1 before Pronase treatment and 65 kDa.nm-1 after treatment. The fuzzy region carries all the epitopes recognized by two different antisera against microtubule-associated protein tau. By contrast, a monoclonal antibody (mAb) we have raised to paired helical filament cores (mAb 423) decorates Pronase-treated filaments much more strongly than it does untreated ones. We have shown in previous papers that the epitope recognized by mAb 423 is carried by a central 9.5-kDa fragment of tau protein, which therefore forms part of the Pronase-resistant core structure. The remainder of the tau protein incorporated into the filaments must contribute part, if not all, of the fuzzy region. The mass per unit length measurements imply that the three-domain structural subunit of the core that we visualized previously by image reconstruction has a molecular mass of approximately equal to 100 kDa.

Alzheimer Disease

Low-dose cyclosporine maintenance therapy after immunosuppressive induction in a rat cardiac transplant model.

An immuno-reduction-suppression protocol using spleen cell infusion followed by cyclophosphamide (CP) or azathioprine (AZ) to reduce the immunocompetent cells and maintenance suppression with low-dose cyclosporine (CsA) was highly effective in a rat cardiac transplant model. Following one or two spleen cell infusions, AZ or CP treatment was given before transplantation. After transplantation the animals were maintained with low-dose CsA. Among those treated with AZ, five of eight survived greater than 100 days, and among those treated with CP, six of eight survived greater than 100. These two protocols were far superior to 28 other permutations of treatment consisting of 164 transplants, such as infusions plus AZ without CsA and infusions without AZ but with CsA. We conclude that CsA can most effectively be used in low dose as a maintenance drug and that immunoreduction therapy is optimized by prestimulation and expansion of reactive cells. Another important feature of this proposal is that the immunoreductive risk phase, performed before transplantation, can be separated from the operative risk period. This avoids the conventional superimposition of the two risks.

Animals

An evaluation of implanted male Onchocerca gibsoni in mice as a screen for macrofilaricides against Onchocerca volvulus.

An in vivo drug screen for identifying new compounds with activity against Onchocerca macrofilariae was developed using male Onchocerca gibsoni implanted subcutaneously in outbred mice. There were several similarities (Mel W, CGP 20376, CGP 6140, levamisole) and two differences (suramin, furapyrimidone) between levels of drug efficacy in this model and activity against natural infections of O. gibsoni and O. volvulus. There was considerable variation in the mouse reaction. This mouse model is a potentially useful primary screen for macrofilaricidal drugs against Onchocerca.

Animals