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Biomedical subjects

M Novak

Publications and source records attributed to M Novak.

At least 109 records · Page 6Linked to original sources

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↗

Studies of high-dose megestrol acetate: potential applications in cachexia.

Cachexia can be a severe problem in the management of patients with cancer and other illnesses because it produces an ever-increasing spiral of anorexia, undernutrition, loss of tissue mass, muscle wasting, and increased susceptibility to infection and treatment toxicity. Megestrol acetate has been observed to produce weight gain in patients with hormone-sensitive tumors and has recently been noted to produce a similar degree of weight gain in those with hormone insensitive tumors. A review of our experience in a phase I-II study of escalating doses of megestrol acetate for advanced breast cancer revealed that weight gain occurred in more than 80% of all treated patients and in 90% of those patients who received treatment for 6 or more weeks. The median maximum weight gain was 5.5 kg, with a range of -5.6 to 44 kg. Subjective improvement in appetite occurred in most patients. These data provided the impetus for a series of further studies of the role of megestrol acetate in the control of cachexia, including a randomized study in cancer cachexia, AIDS cachexia, and anorexia nervosa. In addition, a number of laboratory trials seeking the mechanism of action have been initiated, as well as whole-animal studies to define the compartment of increased weight. Our data and the preliminary observation of weight gain in patients with hormone insensitive tumors suggest that megestrol acetate has a potential role in producing a possibly dose-related subjective improvement and an increase in appetite and weight. Further research is necessary to understand the mechanism of appetite stimulation and anabolic effect.

Body Weight↗

Mast cell responses to Hymenolepis microstoma infection in mice.

Murine mast cells (MC) responded strongly to Hymenolepis microstoma infection. Starting day 7 postinfection (PI) and continuing until the end of the experiment (35 days PI), significantly larger numbers of MC were present in both the duodenum and bile duct of infected mice than in uninfected controls. In animals challenged with 5 cysticercoids 2 wk after primary infection, the MC response in the duodenum, but not in the bile duct, was of even greater degree than in naive hosts. The majority of MC in the duodenum of infected and challenged mice were intraepithelial mucosal MC, whereas in the bile duct the majority were connective tissue MC. Hypertrophy of the duodenal submucosa and of the bile duct wall was noticeable in all infected and challenged hosts. Worms in primary infections were not affected by the host response, but none of the worms in the challenge dose became established. It is postulated that the type of MC involved in specific immune response of the host is the intraepithelial MC, whereas the cell type participating in general inflammatory events is the connective tissue MC.

Animals↗