Search PubMed⌕ Search

Biomedical subjects

J Stoll

Publications and source records attributed to J Stoll.

At least 19 recordsLinked to original sources

Insulin-like growth factor 1 receptor mRNA expression and autophosphorylation in human myometrium and leiomyoma.

Uterine leiomyomas are the most common tumors of the genital tract. Growth factors seem to be implicated in the development of leiomyoma. The aim of this study was to determine insulin-like growth factor 1 receptor (IGF-1-R) mRNA levels and IGF-1-R tyrosine kinase activity in normal myometrium and leiomyoma. Plasma membranes of myometrium and leiomyoma of 14 women subjected to hysterectomy were prepared, and samples were incubated in the absence or presence of recombinant human IGF-1 to assess the tyrosine kinase activity (Western blot). Reverse-transcriptase polymerase chain reaction with specific primers for IGF-1-R was used to determine IGF-1-R mRNA levels. IGF-1-R mRNA levels in myometrium (0.8216 +/- 0.096) and in leiomyoma (0.7905 +/- 0.136) were not statistically significantly different (p = 0.648). The degree of IGF-1-R autophosphorylation stimulated by recombinant IGF-1 was not different in myometrium (1.020 +/- 0.120) and leiomyoma (1.620 +/- 0.656) either (p = 0.075). There was no difference in IGF-1-R expression and IGF-1-R autophosphorylation between normal myometrium and leiomyoma.

Female↗

Prediction of daily milk, fat, and protein production by a random regression test-day model.

Test-day genetic evaluation models have many advantages compared with those based on 305-d lactations; however, the possible use of test-day model (TDM) results for herd management purposes has not been emphasized. The aim of this paper was to study the ability of a TDM to predict production for the next test day and for the entire lactation. Predictions of future production and detection of outliers are important factors for herd management (e.g., detection of health and management problems and compliance with quota). Because it is not possible to predict the herd-test-day (HTD) effect per se, the fixed HTD effect was split into 3 new effects: a fixed herd-test month-period effect, a fixed herd-year effect, and a random HTD effect. These new effects allow the prediction of future production for improvement of herd management. Predicted test-day yields were compared with observed yields, and the mean prediction error computed across herds was found to be close to zero. Predictions of performance records at the herd level were even more precise. Discarding herds enrolled in milk recording for <1 yr and animals with very few tests in the evaluation file improved correlations between predicted and observed yields at the next test day (correlation of 0.864 for milk in first-lactation cows as compared with a correlation of 0.821 with no records eliminated). Correlations with the observed 305-d production ranged from 0.575 to 1 for predictions based on 0 to 10 test-day records, respectively. Similar results were found for second and third lactation records for milk and milk components. These findings demonstrate the predictive ability of a TDM.

Animals↗

On the cause of mental retardation in Down syndrome: extrapolation from full and segmental trisomy 16 mouse models.

Down syndrome (DS, trisomy 21, Ts21) is the most common known cause of mental retardation. In vivo structural brain imaging in young DS adults, and post-mortem studies, indicate a normal brain size after correction for height, and the absence of neuropathology. Functional imaging with positron emission tomography (PET) shows normal brain glucose metabolism, but fewer significant correlations between metabolic rates in different brain regions than in controls, suggesting reduced functional connections between brain circuit elements. Cultured neurons from Ts21 fetuses and from fetuses of an animal model for DS, the trisomy 16 (Ts16) mouse, do not differ from controls with regard to passive electrical membrane properties, including resting potential and membrane resistance. On the other hand, the trisomic neurons demonstrate abnormal active electrical and biochemical properties (duration of action potential and its rates of depolarization and repolarization, altered kinetics of active Na(+), Ca(2+) and K(+) currents, altered membrane densities of Na(+) and Ca(2+) channels). Another animal model, the adult segmental trisomy 16 mouse (Ts65Dn), demonstrates reduced long-term potentiation and increased long-term depression (models for learning and memory related to synaptic plasticity) in the CA1 region of the hippocampus. Evidence suggests that the abnormalities in the trisomy mouse models are related to defective signal transduction pathways involving the phosphoinositide cycle, protein kinase A and protein kinase C. The phenotypes of DS and its mouse models do not involve abnormal gene products due to mutations or deletions, but result from altered expression of genes on human chromosome 21 or mouse chromosome 16, respectively. To the extent that the defects in signal transduction and in active electrical properties, including synaptic plasticity, that are found in the Ts16 and Ts65Dn mouse models, are found in the brain of DS subjects, we postulate that mental retardation in DS results from such abnormalities. Changes in timing and synaptic interaction between neurons during development can lead to less than optimal functioning of neural circuitry and signaling then and in later life.

Animals↗

Permeability characteristics of bovine and human dentin under different pretreatment conditions.

In order to use bovine dentin instead of human dentin for in vitro adhesion and cytotoxicity tests the permeability characteristics of human and bovine dentin should be similar. In the present study hydraulic conductance (Lp) and diffusional water flux (J5) of human and bovine dentin slices were compared. The permeability experiments were performed in a split chamber using tritiated water in physiological saline. Lp and Js of bovine dentin were 0.7- to 2.4-fold and 1.1- to 3.5-fold that of human dentin (not statistically significant). For human and bovine dentin Lp and Js increased with etching and showed an inverse linear relationship (r > or = 0.7) with dentin thickness. The variability of bovine data was low (perfusion = 30%, diffusion = 22%) and about half that of the human data. In conclusion bovine dentin near the cementoenamel junction seems to be a suitable alternative for coronal human dentin for in vitro tests with respect to transdentinal permeability characteristics.

Acid Etching, Dental↗

Treatment of acute low back pain in Wisconsin: results of the State Medical Society's Medical Outcomes Research Project.

BACKGROUND: Acute low back pain is the fifth most common reason for physician visits. Multiple treatment options are available, but not all physicians and patients are satisfied with the results. This study evaluated treatment outcomes from patients' perspectives using standardized measures. METHODS: 368 patients with acute low back pain were enrolled in the study. Only 128 participants (35%) completed all 4 health outcome questionnaires (administered at baseline, 6 weeks, 3 months, and 1 year). RESULTS: Most participants reported improved health at 1-year follow-up,, with the most significant gains achieved by 3 months. However, 40% were not satisfied with their outcome. Patients with radicular low back pain scored lower on health outcome measures than patients without radicular symptoms. CONCLUSION: A sizeable percentage of patients with acute low back pain progress to chronic pain despite therapeutic intervention. Patients with radiculopathy may require nonstandard treatment to avoid unfavorable outcomes.

Acute Disease↗

Ts65Dn mouse, a Down syndrome model, exhibits elevated myo-inositol in selected brain regions and peripheral tissues.

myo-Inositol is elevated in the Down syndrome (DS; trisomy 21) brain and may play a role in mental retardation. In the present study, we examined brain regions and peripheral tissues of Ts65Dn mouse, a recently characterized genetic model of DS, for abnormal myo-inositol accumulation. A GC/MS technique was used to quantitate myo-inositol and other polyol species (ribitol, arabitol, xylitol, and 1,5-anhydrosorbitol) in tissues from the Ts65Dn mice and control diploid mice. myo-Inositol was found to be elevated in frontal cortex, hippocampus, and brain stem but not in cerebellum of the Ts65Dn mouse. Among peripheral organs examined, liver and skeletal muscle were found to excessively accumulate myo-inositol. In all tissues, concentrations of polyol internal controls were normal. The Ts65Dn mouse is useful to study the possible effect of elevated myo-inositol on cellular processes.

Animals↗

Localization on a physical map of the NKC-linked Cmv1 locus between Ly49b and the Prp gene cluster on mouse chromosome 6.

The Cmv1 locus controls NK cell-mediated resistance to infection with murine CMV. Our recent genetic analysis of backcross mice demonstrated that the NK gene complex (NKC)-linked Cmv1 locus should reside between the Ly49 and Prp gene clusters on distal mouse chromosome 6. We have aligned yeast artificial chromosome (YAC) inserts in a contig spanning the interval between the Ly49 and Prp gene clusters. This YAC contig includes 13 overlapping YAC inserts that span more than 2 megabases (Mb) in C57BL/6 (B6) mice. Since we have identified genomic clones that span the Ly49-Prp gene region, we hypothesize that at least one should contain the Cmv1 locus. To narrow the Cmv1 critical region, we developed novel NKC genetic markers and used these to genotype informative backcross and intra-NKC recombinant congenic mouse DNA samples. These data suggest that Cmv1 resides on a single YAC insert within an interval that corresponds to a physical distance of approximately 390 kb. This high resolution, integrated physical and genetic NKC map will facilitate identification of Cmv1 and other NKC-linked loci that regulate NK cell-mediated immunity.

Animals↗

Factors which are associated with dental decay in the older individual.

OBJECTIVES: To improve reliability of salivary bacterial cultures as a surrogate for plaque levels of cariogenic bacterial species by reporting the salivary CFUs of these organisms as a function of the number of teeth. DESIGN: Cross-sectional collection of data in a convenience sample of adults over 60 years of age. SETTING: Hospital Dental clinic, University bacteriology laboratory. SUBJECTS: 523 older dentate subjects, average age 70, including 412 subjects who were in an independent living status and 111 in a dependent-living situation. MAIN OUTCOME MEASURES: Subjects were examined for decay and the presence of salivary factors including the levels of S. mutans, lactobacilli, yeast and other bacteria. The salivary levels of the bacteria were adjusted for the number of teeth in the mouth, and the resultant values were entered into multivariable logistic regression models along with clinical and other salivary parameters. RESULTS: Mutans streptococci levels reported as CFUs/ml saliva per tooth were significantly associated with coronal surface decay, and lactobacilli, reported in a similar way, were significantly associated with root surface decay. Salivary levels of yeasts, which had previously been associated with decay in this population, were no longer significant using this construct. CONCLUSIONS: This construct of reporting salivary bacteriological data as a function of tooth number and per ml saliva could improve the reliability of bacteriological data obtained in epidemiological studies investigating the role of bacteria in dental decay in the elderly.

Candida↗

Downregulation of oxidative phosphorylation in Alzheimer disease: loss of cytochrome oxidase subunit mRNA in the hippocampus and entorhinal cortex.

Messenger RNA (mRNA) for cytochrome oxidase subunit II (COX II) was localized by in situ hybridization in the entorhinal cortex and hippocampal formation of postmortem brain tissue from normal human subjects and from patients with Alzheimer disease (AD). In the control entorhinal cortex, COX II mRNA was detected mainly in neuronal cell bodies of layers II and IV. In control hippocampal formation, highest levels were localized in neuronal cell bodies of the dentate gyrus and the CA3 and CA1 regions, neurons that are involved in the major input and output pathways of the hippocampal formation. In AD brain, COX II mRNA was markedly reduced in the entorhinal cortex and the hippocampal formation compared with control brain. In the AD hippocampal formation, reductions were in regions severely affected by AD pathology as well as in regions that were relatively spared. These results are consistent with the hypothesis that reduced mitochondrial energy metabolism reflects loss of neuronal connections in AD.

Aged↗

Increased expression of voltage-activated calcium channels in cultured hippocampal neurons from mouse trisomy 16, a model for Down syndrome.

Calcium is an important second messenger that affects metabolic and physiological activities of developing and mature neurons. It has been reported that electrical activity is abnormal in cultured hippocampal and DRG neurons from the trisomy 16 (Ts16) mouse, a model for Down syndrome (trisomy 21-Ts21 in human). Whole-cell voltage-clamp, radiolabeled ligand binding techniques and mRNA measurements were used to study the effect of Ts16 on voltage-dependent calcium currents in cultured fetal hippocampal neurons from the Ts16 mouse. In neither Ts16 nor control diploid neurons were low-voltage-activated calcium currents detected. However, a high-voltage-activated (HVA) calcium current was identified and shown to be dihydropyridine sensitive. The density of this HVA calcium current was 80% greater in Ts16 neurons than in control. This difference correlated with a 70% increase in binding of radiolabeled dihydropyridine, PN200-110, a marker of L-type calcium channels. However, mRNA levels encoding the alpha1C and alpha1D subunits were unchanged in the Ts16 neurons. In contrast, mRNA level of the myo-inositol transporter, the gene for which is located on mouse chromosome 16, was elevated in Ts16 neurons due to a gene-dosage effect. Therefore, it is likely that posttranscriptional regulation of dihydropyridine-sensitive voltage-dependent calcium channels is abnormal in Ts16. As dihydropyridine sensitive HVA Ca channels are implicated in heterosynaptic long-term depression and long-term potentiation, the differences reported here, if also present in the Down syndrome brain, may contribute to mental retardation in that disorder.

Animals↗

16-Epiestriol, a novel anti-inflammatory nonglycogenic steroid, does not inhibit IFN-gamma production by murine splenocytes.

All the steroidal anti-inflammatory drugs currently available are glucocorticoids. The desired anti-inflammatory activities of glucocorticoids frequently are accompanied by adverse side effects, notably glycogenic activities and profound immunosuppression, that can limit clinical use. We recently identified 16-epiestriol, a naturally occurring steroid, as exhibiting significant anti-inflammatory activity without glycogenic activity. In the present study, we compared the effects of 16-epiestriol and hydrocortisone on the capacity of murine splenocytes to produce interferon-y (IFN-y). We injected young adult male BDF1 mice once with 20 mg/kg hydrocortisone or 20, 5, or 1 mg/kg 16-epiestriol and 4 h later harvested the splenocytes. Flow cytometric analysis confirmed that 16-epiestriol did not alter the number of CD3+ T cells in the spleen. In contrast to the suppressive effects of hydrocortisone, none of the 16-epiestriol concentrations inhibited concanavalin A-stimulated IFN-gamma production by spleen cells, as determined by ELISA. Incubating spleen cells from untreated mice in concentrations of 16-epiestriol ranging from 1 mg/ml to 100 pg/ml did not alter profiles of IFN-gamma production, in contrast to the suppressive dose-response effects of hydrocortisone. Collectively, these results support the contention that 16-epiestriol may be a clinically useful safe anti-inflammatory steroid without profound immunosuppressive activities.

Adjuvants, Immunologic↗

The Ly-49 family: regulation of cytokine production in murine NK cells.

Most proteins encoded by members of the Ly-49 gene family are class I-recognizing receptors on murine natural killer (NK) cells. Class I recognition by Ly-49 receptors usually results in inhibition of NK cell lysis of target cells. However, NK cells function not only in a lytic capacity, but also can mediate cytokine production. In this report we have demonstrated the ability of Ly-49A and Ly-49G2 to inhibit production of cytokines by NK cells by showing that specific antibodies against these gene products stimulate cytokine production. Murine NK cells were cultured in the presence of P815 (H2-Dd), and supernatants were analyzed for the production of interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and granulocytemacrophage colony-stimulating factor (GM-CSF). NK cell populations were sorted for Ly-49A+ or Ly-49G+ subsets, and these subsets were analyzed for their ability to alter cytokine induction by target cell interaction. In the presence of target cells expressing the appropriate class I molecules, Ly-49A and G2 were found to inhibit cytokine induction by NK cells. Examination of mRNA for IFN-gamma and GM-CSF indicated that Ly-49 receptors increased mRNA levels of NK cells. These results demonstrate that class I binding of these NK receptors can inhibit production of important physiological cytokines, in addition to the regulation of cytotoxic activity.

Animals↗

Neuronal activity and early neurofibrillary tangles in Alzheimer's disease.

We studied neuronal activity and its relation to the accumulation of neurofibrillary tangles in Alzheimer's disease (AD) neurons by in situ hybridization to cytochrome oxidase subunit III messenger RNA, a marker of mitochondrial energy metabolism. In AD midtemporal cortex, levels of cytochrome oxidase subunit III messenger RNA were decreased by 26% in neurons bearing early-stage neurofibrillary tangles as compared to tangle-free neurons (p < 0.01). However, levels of 12S ribosomal RNA, also encoded by mitochondrial DNA, and of total messenger RNA were decreased only in later stages of tangle development. Comparing tangle-free neurons of 4 AD brains to tangle-free neurons of 3 control brains, levels of cytochrome oxidase subunit III messenger RNA were found to be 25% lower (p < 0.001) in AD tangle-free neurons. Because energy metabolic needs of neurons are mainly determined by synaptic input, the observed decreases in cytochrome oxidase subunit III messenger RNA likely reflect downregulation due to impaired synaptic function in AD. Thus, a failure in synaptic transmission may precede tangle formation. A further decline in neuronal activity is seen as tangle formation progresses. However, these results can also be viewed as showing the viability and continuing activity, albeit at a lower level, of neurons in the early stages of neurofibrillary pathology.

Aged↗

Reduced expression of voltage-gated sodium channels in neurons cultured from trisomy 16 mouse hippocampus.

Voltage-gated sodium channels are responsible for the initial depolarizing phase of the action potential. In hippocampal neurons cultured from trisomy 16 (Ts16) mice (a model for Down's syndrome), the maximum inward conductance mediated by these channels was reduced 47% relative to control diploid neurons. This reduced conductance was reflected in a 35% decrease in binding of radiolabeled saxitoxin, a sodium channel-specific ligand, indicating expression of fewer channels in these neurons. The mRNAs encoding the alpha and beta 1 subunits were, however, present at the same levels in Ts16 neurons and control diploid neurons. Thus, the altered regulation of voltage-gated sodium channels in Ts16 neurons is apparently a post-transcriptional event and possible mechanisms are discussed.

Animals↗

Factors which influence levels of selected organisms in saliva of older individuals.

The most commonly measured bacterial parameters in saliva are the levels of the mutans group streptococci and lactobacilli, which have diagnostic implications for the incidence of dental decay. Diagnostic guidelines which are applicable to children and young adults in whom most, if not all, teeth are present and in whom the rate of stimulated saliva is almost always greater than 0.5 ml/min have been developed. Dental decay is a potential health problem of considerable magnitude among elderly individuals. In elderly individuals, missing teeth, the presence of dentures, and a reduced salivary flow could confound the interpretation of salivary levels of cariogenic bacteria. In the present study, in which saliva was collected from more than 560 elderly individuals (average age, 70 +/- 8 years), there was a significant positive relationship between the salivary levels of Streptococcus mutans and increased numbers of teeth. There was a positive association between the salivary levels of S. mutans and decay when the data were stratified for the presence of a complaint of xerostomia and the presence of dentures. However, a similar analysis indicated that lactobacilli and yeasts were more likely to be associated with decay. The various variables which could influence the bacterial counts per milliliter of saliva, e.g., independent or dependent living status, complaint of xerostomia, stimulated salivary flow, salivary pH, the presence of dentures, number of teeth, and decay, were analyzed simultaneously by using a multivariable linear model. In that analysis the number of decayed teeth was significantly associated with the presence of lactobacilli (P = 0.0001) and yeasts (P = 0.025) but not with the presence of S. mutans. Our findings indicate that salivary levels of lactobacilli and yeasts, as well as the salivary levels of S. mutans, should be monitored when seeking microbial indicators that might predict the incidence of caries in elderly individuals.

Activities of Daily Living↗

Long-term intracerebral transplants of fetal hippocampus from mouse trisomy 16, a model for Down's syndrome (trisomy 21), do not exhibit Alzheimer's disease neuropathology by ultrastructural criteria .

Murine trisomy 16 (Ts16) is an animal model for Down's syndrome (human trisomy 21), because mouse chromosome 16 is genetically homologous to human chromosome 21. Down's syndrome patients, older than 35 years, demonstrate the neuropathological and neurochemical defects characteristic of Alzheimer's disease and Ts16 mouse fetuses exhibit phenotypic abnormalities similar to those in Down's syndrome fetuses. Trisomic mouse fetuses, however, die in utero, and so do not survive long enough for their brains to develop the degenerative changes of aging. This can be overcome by grafting the fetal Ts16 hippocampus (an early site for the development of the pathological features characteristic of Alzheimer's disease), into the cerebral ventricle or striatum of a normal adult mouse host. We have made such transplants, which have survived for up to 12 months. Examining these grafts ultrastructurally at various stages from 1 to 12 months, and comparing them with normal control grafts, reveals no structural difference that could be deemed characteristic of Alzheimer disease; no neurofibrillary tangle or senile plaque was observed. These observations, together with the normal structure of the neuronal organelles in trisomic hippocampal tissue, suggest that trisomic mouse grafts are not a useful model for Alzheimer's disease, despite earlier reports to the contrary.

Alzheimer Disease↗

Impairment in mitochondrial cytochrome oxidase gene expression in Alzheimer disease.

Brains from 5 patients with Alzheimer's disease (AD) showed a 50%-65% decrease in mRNA levels of the mitochondrial-encoded cytochrome oxidase (COX, a marker of oxidative metabolism) subunits I and III in the middle temporal association neocortex, but not in the primary motor cortex, as compared to 5 control brains. The amount of mitochondrial-encoded 12S rRNA was not altered, nor was the amount of nuclear-encoded lactate dehydrogenase B mRNA (a marker of glycolytic metabolism). These data suggest that the decrease in COX I and III subunits mRNA in affected brain regions may contribute to reduced brain oxidative metabolism in AD.

Actins↗