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Biomedical subjects

M Novak

Publications and source records attributed to M Novak.

At least 91 records · Page 5Linked to original sources
PubMed1992

A comparison of the impact of institutionalization on spouse and nonspouse caregivers.

We report on a study of 106 spouse and nonspouse primary caregivers of cognitively impaired older people. Half of these caregivers cared for someone in a community setting, half cared for someone in an institution (a nursing home or hospital). The study used the multidimensional Caregiver Burden Inventory (CBI) to measure the burden that these caregivers felt. A 2 x 2 multivariate analysis of variance found an effect of the interaction of relationship and living arrangement on two CBI subscales: Time Dependence Burden and Developmental Burden. Spouses showed a significantly greater difference in Time Dependence Burden scores than did nonspouses in both living arrangement groups, and nonspouses showed a significantly greater difference in Developmental Burden than did spouses in both groups. We conclude with a discussion of how programs can help different types of caregivers cope with feelings of burden.

Analysis of Variance↗
PubMed1991

One-step method for establishing 8-azaguanine-resistant hybridomas suitable for the preparation of triomas.

A simple and rapid one-step method for establishing azaguanine resistant (Agr) hybridomas, which can be used as a fusion partner for the construction of triomas (hybridoma x splenocyte), has been developed. The method relies on cloning the hybridoma cells in soft agar supplemented with 20 micrograms/ml 8-azaguanine. The drug-resistant subclones were isolated after 3-5 days, in comparison with 4-5 weeks reported for the conventional adaptation method. The high frequency (about 10(-3) of Agr-mutants achieved by the cloning method was demonstrated with five different hybridoma clones. One of the derived Agr-hybridomas was fused with mouse immune spleen cells in order to demonstrate its suitability for the generation of triomas secreting bispecific monoclonal antibodies.

Animals↗
PubMed1991

Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51.

The microtubule-associated protein tau that is incorporated into paired helical filaments (PHFs) undergoes some form of aberrant posttranslational processing in Alzheimer disease. Difficulties in deciding which changes are critical for PHF formation stem in part from the lack of immunochemical markers specific for PHF tau. The only monoclonal antibody (mAb) that is known to react with PHF tau but not with the predominant normal adult tau species is mAb 423. Another mAb (7.51, described in this paper) recognizes a segment of tau that is included in the minimal recognition unit required by mAb 423. Unlike 423, which is PHF tau-specific, mAb 7.51 recognizes all PHF core-derived tau as well as native soluble tau and recombinant tau expressed in bacteria and so serves as a generic tau marker. Both epitopes are in the 12-kDa fragment released from the Pronase-resistant core of the PHF (which encompasses the tandem repeat region). The mAb 7.51 epitope requires segments located in the last two repeats, which are common to all tau isoforms. The mAb 423 epitope requires sequences located near both the N and the C terminus of the 12-kDa fragment common to three- and four-repeat tau isoforms. Fragments denatured by concentrated formic acid and SDS regain 423 reactivity when denaturing agents are removed. Since the primary amino acid sequences of PHF tau and normal tau are identical in the repeat region, we conclude that 423 reactivity also requires a modification(s) occurring within an approximately 90-residue segment that are not present in tau proteins so far described in the human brain.

Alzheimer Disease↗
PubMed1991

Measurement of distinct immunochemical presentations of tau protein in Alzheimer disease.

The tau protein is a microtubule-associated protein that is normally located in nerve axons. In Alzheimer disease, it is a constituent of paired helical filaments (PHFs), which are the principal fibrous component of the characteristic neurofibrillary tangles. The tau protein, therefore, is abnormally sequestered in an insoluble form in PHFs in the cell body and dendrites in Alzheimer disease. We have used two monoclonal antibodies (mAbs) to selectively measure the levels of normal, soluble tau protein and of PHF-associated tau protein in the brain. mAb 423 binds to PHFs and recognizes a 12-kDa fragment of tau protein released by formic acid treatment of PHFs, but it does not recognize normal tau protein. In contrast, mAb 7.51 recognizes normal tau protein as well as the PHF core-derived tau fragment, but its epitope is concealed in the PHF-bound form. The differential binding properties for these two mAbs have enabled us in this study to quantify insoluble PHF-associated tau protein in the somatodendritic compartment as well as normal soluble tau protein in its predominantly axonal location. Our findings demonstrate that a distinct immunochemical presentation of tau protein recognized by mAb 423, a PHF-specific marker, can be used to quantify neurofibrillary pathology in Alzheimer disease independently of the presence of normal tau proteins.

Alzheimer Disease↗
PubMed1991

Identification of 3- and 4-repeat tau isoforms within the PHF in Alzheimer's disease.

The microtubule associated protein tau is incorporated into the pronase resistant core of the paired helical filament (PHF) in such a way that the repeat region is protected from proteases, but can be released as a major 12 kDa species from the PHF core by formic acid treatment and by boiling in SDS. This fragment retains the ability to aggregate in the presence of SDS. Detailed sequence analysis of the 12 kDa species shows that it consists of a mixture of peptides derived from the repeat region of 3- and 4-repeat tau isoforms comigrating as a single electrophoretic band. However, the 4-repeat isoforms released from the core lack either the first or the last repeat. The pronase-protected region of tau within the PHF core is therefore restricted to three repeats, regardless of isoform. The alignment of cleavage sites at homologous positions within tandem repeats after protease treatment indicates that the tau-core association is precisely constrained by the tandem repeat structure of the tau molecule.

Alzheimer Disease↗
PubMed1991

Mesocestoides corti: a GC/MS study of the effects of oxaloacetate and iodoacetate on the isotope ratios in succinate and lactate excreted in the presence of NaH13CO3.

The current study was undertaken to gain further insight into the carbohydrate metabolism of the proliferating larvae of Mesocestoides corti by studying the effect of the metabolic inhibitors oxaloacetate and iodoacetate on the incorporation of label from NaH13CO3 into the excretory products lactate and succinate. These products were converted to their methyl derivatives and analyzed by gas chromatography/mass spectrometry (GC/MS) to determine the isotope ratios. The percentage of [1-13C]lactate, [1-13C]succinate, and [1,4-13C2]succinate decreased in the presence of oxaloacetate; iodoacetate did not significantly influence the relative amount of the former, but markedly increased percentages of the latter two. The data provide information on the relative rates of the pathways and steps within them and the influence of the inhibitors on these pathways.

Animals↗
PubMed1991

A nuclear magnetic resonance study of the glucose metabolism of Hymenolepis diminuta exposed to histamine and serotonin in vitro.

The direct effects of the inflammatory mediators, histamine (HI) and serotonin (SE), on the glucose metabolism of Hymenolepis diminuta in vitro were studied by analyzing the excretory products from culture media, containing D-1-13C-glucose and various concentrations of HI and/or SE, by 1H-nuclear magnetic resonance (n.m.r.) spectroscopy. The results revealed that HI markedly accelerated the glycolysis process by increasing the amount of lactate production. The increased glycolytic activity was reflected in a concentration-dependent increase in glucose uptake. Excretion of acetate was also stimulated by HI. A low concentration of SE significantly increased succinate, acetate and lactate excretions, whereas a high concentration had little effect on lactate production and significantly decreased succinate and acetate excretions. A combination of HI and SE treatment at a low concentration had no significant effect, but at a high concentration showed an additive effect, with an increase in lactate production, a decrease in succinate production and an increase in glucose uptake. Thus this work confirms that HI and SE directly influence, albeit differently, energy metabolism of the tapeworm H. diminuta.

Animals↗
PubMed1991

Mapping of two immunodominant structures on human interferon alpha 2c and their role in binding to cells.

Structure-function studies of human recombinant interferon (IFN) alpha 2c were performed using a panel of specific monoclonal antibodies in the binding and neutralizing assays. Two immunodominant structures, designated sites I and II, were detected and localized within two conserved hydrophilic regions of IFN-alpha molecule. Using the NK2 antibody as a marker, site I was mapped into a carboxy-terminal domain around residues 112-148. This site was shown to be, most probably, responsible for inducing the antiviral and antiproliferative activities of the receptor-bound IFN-alpha 2c in the cell. Site II that mapped into the amino-terminal domain of IFN-alpha 2c was, at least partially, formed by the amino acid residues 36-41. This region was shown to be most probably involved in the binding of IFN to its cellular receptor. These findings fit with Sternberg and Cohen's model (Int. J. Biol. Macromol. 4, 137-144, 1982) for the tertiary structure of human IFN-alpha.

Animals↗
PubMed1991

A progressive deposition of paired helical filaments (PHF) in the brain characterizes the evolution of dementia in Alzheimer's disease. An immunocytochemical study with a monoclonal antibody against the PHF core.

Using the monoclonal antibody (mAb) 6.423 which recognizes epitopes of the pronase-resistant core of paired helical filaments (PHF), we studied postmortem frontal cortex from Alzheimer's disease (AD) patients with short (Group II) and long (Group III) histories of clinical dementia. Four cases with clinically unconfirmed dementia and a postmortem diagnosis of AD (Group I) were also studied. In Group I, the 6,423 mAb was negative whereas in Group II, the antibody recognized primarily neurofibrillary tangles (NFT). In contrast, brains in Group III contained a dense network of 6,423-immunoreactive (IR) thread-like structures ("ghost" neurites) and plaque-like structures with granular appearance, in addition to NFT. The number of 6,423-IR structures appeared to be related to the duration of clinical dementia and the age of onset. Furthermore, "ghost" neurites were more abundant in young AD cases. The possible significance of the 6,423-IR pattern in the pathogenesis of AD is discussed.

Adult↗
PubMed1991

Lyme disease: the picture in Iowa.

Lyme disease in Iowa increased sharply in 1989 and 1990, creating concern in Iowans who spend considerable time out-of-doors. The authors review the history of Lyme disease and its symptoms and present an update on the status of Lyme disease and its tick vector in Iowa.

Animals↗
PubMed1991

Sequestration of tau by granulovacuolar degeneration in Alzheimer's disease.

Antibodies directed against three regions of tau have been used in a histologic study of granulovacuolar degeneration (GVD) in Alzheimer's disease (AD). Granulovascular degeneration complexes, consisting of a dense granule in a less-dense vacuole, were found in hippocampal pyramidal neurons in all patients studied. Anti-tau antibodies directed against the N-and C-termini, and the repeat region of tau, were found to immunolabel the granule of the GVD complex. Intracellular neurofibrillary tangles also were labeled by these antibodies. In particular, MAb6.423, which recognizes tau protein sequestered in paired helical filaments (PHF) in AD, but not the normal tau proteins so far described in human brain, labeled GVD granules. Contrarily, a generic tau marker (MAb7.51), which immunolabels all known isoforms of isolated and expressed tau protein, including PHF-tau, did not label the GVD granule. These findings demonstrate that the entire tau molecule is sequestered within the GVD granule, and that the tau protein found in GVD complexes is antigenically related to that found in PHFs. There is, however, a difference in the way in which the repeat region of tau is incorporated into the two structures, making the MAb7.51 epitope unavailable in the GVD complex. These findings suggest that the formation of GVD complexes in hippocampal pyramidal neurons vulnerable to neurofibrillary degeneration may represent an alternative pathway for dealing with an aberrant molecular complex, which contributes to the formation of GVD granules and neurofibrillary tangles in AD.

Adult↗
PubMed1991

Echinococcus multilocularis--a model for imaging research.

Magnetic resonance images of transverse, sagittal, and coronal sections of Meriones unguiculatus abdomens experimentally infected with Echinococcus multilocularis revealed alveolar cyst masses that were especially prominent in the late phase of infection.

Animals↗
PubMed1990

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↗
PubMed1990

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↗
PubMed1990

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↗