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Biomedical subjects

M Novak

Publications and source records attributed to M Novak.

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

Replication of human cytomegalovirus in a rhabdomyosarcoma cell line depends on the state of differentiation of the cells.

The replication of human cytomegalovirus (HCMV) was investigated in a new human rhabdomyosarcoma cell line (KFR) with morphological and biochemical characteristics of fetal striated muscle precursors (rhabdomyoblasts). KFR cells exhibited the unique property for spontaneous morphological transformation from a poorly-differentiated state into well-differentiated (myotube-like) rhabdomyoblasts. The poorly-differentiated rhabdomyoblasts promoted both complete viral gene expression and the production of infectious virus. In contrast, in well-differentiated rhabdomyoblasts HCMV infection was abortive. The results showed that replication of HCMV in this human rhabdomyosarcoma cell line depended on the state of cellular differentiation.

Antigens, Viral↗
PubMed1994

The boneless neonate: a severe form of achondrogenesis type I.

We report a case of a severe form of achondrogenesis type I. Prenatal ultrasonography showed a micromelic fetus; bony structures could not be identified. Postnatal radiographs revealed some foci of ossification in the ossa ilia, the clavicles, the upper and the lower jaw and the base of the skull. The long bones, the vertebral column and the ribs were not visible. The diagnosis was established by histologic examination of the growth plates.

Achondroplasia↗
PubMed1994

Mucosal immunity and strategies for novel microbial vaccines.

Infectious diseases continue to be the leading cause of morbidity and mortality worldwide. Increased awareness of the fact that mucosal membranes are the most frequent portals of entry of pathogenic microorganisms has prompted studies aimed at the development of vaccination protocols and antigen delivery systems that would lead to an increased protection of mucosae. Although systemic and strictly local immunizations are of limited effectiveness in the induction of mucosal protection, ingestion or inhalation of antigens results in a generalized immune response manifested by the appearance of specific antibodies of the secretory immunoglobulin (Ig) isotype in external secretions due to the dissemination of IgA precursor cells from IgA-inductive lymphoid tissues. Furthermore, additional inductive sites strategically positioned at the opening of the respiratory and digestive tracts may also be suitable targets for induction of immune responses at desired effector sites. To prevent degradation and the increase of ingested antigens absorption, novel strategies including enclosure of antigens into biodegradable microspheres, liposomes or their expression in viral and bacterial vectors and plants are currently being considered. Forthcoming technological advances in antigen preparation and routes of delivery will undoubtedly have a profound impact on immunization practices in the future.

Animals↗
PubMed1994

Nursing assistant burnout and the cognitively impaired elderly.

This article employs the cognitive appraisal model to examine the experience of burnout in a random sample of nursing assistants (N = 245). The three subscales of Maslach's Burnout Inventory--Emotional Exhaustion, Personal Accomplishment, Depersonalization--serve as the dependent variables in this study. The study found that both stressor and appraisal variables influence feelings of burnout. The stressor variable, frequency of disturbing patient behaviors, best explained feelings of reduced Personal Accomplishment. The appraisal variable, reaction to patient behaviors, best explained Emotional Exhaustion and contributed to the explanation of reduced Personal Accomplishment. Age, minutes spent giving physical care, appraisal of work tasks, and reaction to patient behavior, explained Depersonalization. The study found support for the cognitive appraisal model in that appraisal played an important role in determining burnout. The article concludes with some suggestions for relief of nursing assistant burnout.

Adult↗
PubMed1993

Molecular characterization of the minimal protease resistant tau unit of the Alzheimer's disease paired helical filament.

The Alzheimer's disease paired helical filament (PHF), after digestion with Pronase, retains its characteristic morphological features. We term this the protease resistant core PHF. A 12 kDa tau fragment can be released from the core as an essentially pure preparation. Sequence analysis of this fragment revealed six distinct N-termini beginning in the repeat region of tau. The precise C-terminus is unknown, but the fragment is approximately 100 residues long. A monoclonal antibody, mAb 423, which recognizes the core PHF and the 12 kDa tau fragment, does not recognize normal full-length tau. We describe cDNA synthesis and expression of candidate 12 kDa tau analogues which permit the mapping of the mAb 423 epitope. mAb 423 recognizes all and only those analogues which terminate at Glu391, which lies beyond the homology repeat region. Addition or removal of a single residue at the C-terminus abolishes immunoreactivity. Therefore, mAb 423, together with knowledge of the N-terminus, can be used to measure the precise extent of 12 kDa PHF core tau fragment which we term the minimal protease resistant tau unit of the core PHF. This unit is 93-95 residues long, which is equivalent to three repeats, but is 14-16 residues out of phase with respect to the maximum homology organization of the repeat region. mAb 423 labels isolated PHFs prior to Pronase digestion and intracellular granular and neurofibrillary degeneration in Alzheimer's disease tissues. The constraints which determine endogenous truncation at Glu391 appear to be characteristic of an assembled configuration of tau, either within the PHF or its precursor.

Alzheimer Disease↗
PubMed1993

1H NMR study of metabolic alterations in the small intestine of rats infected with Hymenolepis diminuta.

1H NMR spectra of the duodenum, jejunum and ileum tissues of the small intestine of a rat showed metabolic gradients. 2. The concentrations of metabolites in these gut regions were altered by the presence of the tapeworm Hymenolepis diminuta. 3. In the infected duodenum there was significantly less glycogen, glucose and phosphocreatine/creatine, but significantly more lactate than in the corresponding controls. 4. Infected jejunum contained significantly less betaine but significantly more succinate, alanine and lactate. 5. Infected ileum had significantly less glycogen and taurine but significantly more alanine and lactate.

Animals↗
PubMed1993

Proton nuclear magnetic resonance analysis of liver metabolites from mice infected with Mesocestoides vogae.

Proton NMR spectra of liver extracts from mice infected with Mesocestoides vogae for 24 or 133 days showed differences in the concentrations of liver metabolites when compared to those of normal liver. Moderately infected livers (24 d.p.i.) had significantly less glucose and significantly more glycine, cholines, alanine and lactate than uninfected controls. Similar changes in the concentrations of these metabolites were also found in mice with heavily infected livers (133 d.p.i.), and, in addition, there was significantly more succinate in this group than in the other 2 groups. Furthermore, the heavily infected livers contained more taurine and less acetate than the controls. Tetrathyridia extracts were rich in glycogen and contained high levels of betaine.

Animals↗
PubMed1993

Phosphorus metabolites of liver from mice infected with Hymenolepis microstoma.

31P NMR in vivo spectra of mouse livers infected with Hymenolepis microstoma for 130 or 265 days showed modifications in phosphorus-containing metabolite ratios when compared to those of normal liver. After 130 days of infection the metabolite ratio of inorganic phosphate (Pi)/beta ATP significantly increased whereas that of phosphocreatine (PCr)/beta ATP significantly decreased. In older, 265 day infections, the increase in Pi/beta ATP and decrease in PCr/beta ATP persisted. Changes in the group infected for 130 days were accompanied by lowered pH. Analysis of liver extracts from mice with 130-day-old. H. microstoma revealed significantly lower concentrations of Pi, ATP and ADP compounds. In those from mice infected for 265 days the concentration of Pi remained low whereas concentrations of ATP and ADP increased to levels in between those of controls and the 130-day-old infection. In addition, levels of phosphorylethanolamine (PE) and of an unknown metabolite significantly increased in this latter group. Worm extracts contained high levels of glycerophosphorylcholine (GPC), Pi, fructose 1,6-diphosphate (FDP), PE, diphosphodiesters (DPDE), phosphorylcholine (PC) and glycerolphosphorylethanolamine (GPE) in order of declining concentrations, respectively.

Adenosine Triphosphate↗
PubMed1993

Murine model for evaluation of protective immunity to influenza virus.

We have characterized a murine model as an inexpensive, readily available and sensitive animal model for the evaluation of protective immune responses induced by various routes of administration of influenza A vaccine preparations. Using a non-mouse-adapted human influenza virus to infect unanaesthetized animals intranasally, we established that the optimum dose for infection of Balb/c mice was 10(4) plaque forming units of virus and that the optimum sampling time for measurement of virus yields in the organs of the respiratory tract was 72 h after challenge. We found that the infection was initiated in the nose and progressed by descending into the trachea and lungs over a period of days. Evaluation of protection against infection clearly showed that the tissues of the mouse respiratory tract were completely protected after administration of whole killed virus intranasally and partly protected when virus was administered subcutaneously. The protection correlated with the level of virus-specific IgA antibodies in saliva.

Administration, Intranasal↗
PubMed1993

Oral immunization with influenza virus in biodegradable microspheres.

Polymeric microspheres were evaluated as an oral antigen delivery system for immunization with influenza virus. The immune responses obtained were compared after either oral or systemic immunization of BALB/c mice using purified, formalin-inactivated influenza virus type A/H3N2, either encapsulated in biodegradable and biocompatible microspheres or free in solution. The immunogenicity of formalin-treated influenza vaccine was preserved during the microencapsulation process, and the microencapsulated antigen induced protective immune responses after systemic immunization that were equal to or higher than those induced by conventional vaccine. When administered orally to primed animals, microencapsulated antigen induced levels of anti-influenza antibodies in saliva that were higher than and in serum that were comparable to those obtained by systemic immunization. Furthermore, oral booster immunization provided virtually complete protection of animals challenged with live virus.

Administration, Oral↗
PubMed1993

Microencapsulated human parainfluenza virus induces a protective immune response.

Human parainfluenza type 3 (PI3) virus was incorporated into microspheres composed of a biocompatible and biodegradable DL-lactide and glycolide copolymer. Sera from mice immunized with these microspheres showed an antibody response to the viral glycoproteins and neutralized virus infectivity. The microspheres were also evaluated by intraperitoneal, oral, or intranasal administration to determine their protective efficacy in the hamster. After challenge infection of the intraperitoneally immunized hamsters with live PI3 virus, a significant reduction of virus titers in the respiratory tract was observed, demonstrating the protective efficacy of the microencapsulated viral antigens.

Administration, Intranasal↗
PubMed1992

Molecular characterization and measurement of Alzheimer's disease pathology: implications for genetic and environmental aetiology.

The neuropathological changes seen in Alzheimer's disease represent an interaction between the ageing process in which normal intellectual function is retained, and changes which are specifically associated with severe cognitive deterioration. Molecular analysis of these changes has tended to emphasize the distinction between neurofibrillary pathology, which is intracellular and highly correlated with cognitive deterioration, and the changes associated with the deposition of extracellular amyloid, which appears to be widespread in normal ageing. Extracellular amyloid deposits consist of fibrils composed of a short 42 amino acid peptide (beta/A4) derived by abnormal proteolysis from a much larger precursor molecule (APP). The recent demonstration of a mutation associated with APP in rare cases with familial dementia, neurofibrillary pathology in the hippocampus and atypical cortical Lewy body pathology raises the possibility that abnormal processing of APP could be linked directly with neurofibrillary pathology. Neurofibrillary tangles and neuritic plaques are sites of dense accumulation of pathological paired helical filaments (PHFs) which are composed in part of an antigenically modified form of the microtubule-associated protein tau. The average brain tissue content of PHFs measured biochemically does not increase in the course of normal ageing but increases 10-fold relative to age-matched controls in patients with Alzheimer's disease. There is also a substantial (three-fold) disease-related decline in normal soluble tau protein relative to age-matched controls. This intracellular redistribution of a protein essential for microtubule stability in cortico-cortical association circuits may play an important part in the molecular pathogenesis of dementia in Alzheimer's disease. The role of abnormal proteolysis of APP in this process remains to be elucidated. Immunohistochemical studies on renal dialysis cases have failed to detect evidence of neurofibrillary pathology related to aluminium accumulation in brain tissue. Nevertheless it needs to be seen whether more sensitive biochemical assays of neurofibrillary pathology can demonstrate evidence of an association with aluminium.

Alzheimer Disease↗
PubMed1992

Metabolites of alveolar Echinococcus as determined by [31P]- and [1H]-nuclear magnetic resonance spectroscopy.

[31P]-Nuclear magnetic resonance (NMR) in vivo spectra of Echinococcus multilocularis cysts growing subcutaneously in Meriones unguiculatus showed prominent signals due to phosphomonoesters (PME), phosphodiesters (PDE), inorganic phosphate (Pi) and the alpha, beta and gamma phosphate groups of adenosine triphosphate (ATP). The internal pH of the parasite cysts was 6.7-6.8. The 31P spectra of extracts of these subcutaneous cysts showed peaks identified as glucose-6-phosphate (Glu-6-P), glycerol-3-phosphate (Gly-3-P), phosphorylethanolamine (PE), adenosine-5'-monophosphate (5'-AMP), nicotinamide adenine dinucleotide phosphate (NADP), phosphorylcholine (PC), Pi, glycerolphosphorylethanolamine (GPE), glycerolphosphorylcholine (GPC), phosphoenolpyruvate (PEP), adenosine diphosphate (ADP), ATP and diphosphodiesters (DPDE). These metabolites were also detected at comparable concentrations in the extracts of intraperitoneally grown cysts. In addition, significantly more phosphocreatine (PCr), probably of host origin, was detected in the subcutaneous cysts than in the intraperitoneal cysts. [1H]-NMR spectra of cyst extracts revealed that parasites grown in the abdominal cavity contained significantly less glucose but significantly more succinate, acetate, alanine and beta-hydroxybutyrate. Glycogen, creatine, glycine, taurine, betaine, cholines and lactate were present at similar concentrations in cyst material from both locations.

Adenosine Triphosphate↗
PubMed1992

Conformation-dependent accessibility of the linear epitopes located on the rabies virus glycoprotein.

Seven monoclonal antibodies (MAbs) were derived from mice immunized with the rabies virus glycoprotein of the Pitman-Moore (PM) strain. These antibodies recognized at least five partially overlapping sites located in one immunodominant region. A panel of MAbs was then used to characterize antigenic relationship between PM strain and SAD-Vnukovo strain of these rabies viruses. In immunoblot, all tested antibodies bound to the glycoprotein of both rabies strains, indicating shared antigenic determinants located on the corresponding immunodominant regions. The pattern of reactivity in immunoblot suggested the specificity of antibodies against linear epitopes. However, the supposed close antigenic relation between PM and SAD-Vnukovo strains (evidenced by immunoblot) was not fully confirmed by immunoenzymatic assay. Data provided by ELISA demonstrated two distinct patterns of MAbs reactivity with both antigens. Four antibodies showed specificity for PM strain glycoprotein only, while three MAbs bound with both PM and SAD-Vnukovo strain antigens. We supposed the strain-specific conformation of the native glycoprotein to be responsible for selective access of single MAbs to the respective common linear epitopes.

Animals↗
PubMed1992

The role of support in alleviating stress among nursing assistants.

This paper provides a direct test of the buffering hypothesis that the negative effects of stressors (measured as burden, burnout, and perceived job pressure) on nursing assistants working in long-term care institutions are moderated by social support (at work and external to work). The buffering hypothesis was not confirmed, though some support for a main effects view was found. Social support at work, specifically training to work with residents with cognitive impairment, and support from family and friends can assist nursing assistants in dealing with burnout and perceived job pressure. However, major steps in alleviating burden, burnout, and perceived job pressure must be to decrease or change the workload and provide rewards on the job.

Adult↗
PubMed1992

The effects of mate removal on pregnancy success in prairie voles (Microtus ochrogaster) and meadow voles (Microtus pennsylvanicus).

The effects of removing the stud male have not been controlled in many studies relating pregnancy block to the presence of an unfamiliar male. We examined the effects of removing the male on pregnancy success in prairie voles and meadow voles, two species that differ in degree of paternal investment. Whereas prairie vole males provide extensive care to offspring and accelerate pup development, meadow vole males display little or no care and delay development of pups. We predicted that removal of the stud male would decrease pregnancy success in prairie voles and either have no effect or increase success in meadow voles. In experiment 1, females were in male-induced estrus, and their mates were either left with them or were removed 4 h, 1 day, 2 days, or 8 days after mating. In experiment 2, females were in postpartum estrus, and their mates were either left with them or were removed 1 day, 2 days, or 8 days after birth of their first litter. Removal of the male soon after mating in postpartum estrus decreased pregnancy success in prairie voles and increased success in meadow voles. Thus, although removal of the stud male influenced litter production, the direction of the effect varied with species.

Animals↗