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Biomedical subjects

M Schultz

Publications and source records attributed to M Schultz.

At least 37 records · Page 2Linked to original sources
PubMed2000

The effectiveness of 10% chlorhexidine varnish treatment on dental caries incidence in adults with dry mouth.

OBJECTIVES: This study compared a 10% chlorhexidine varnish treatment with placebo and sham treatments for preventing dental caries in adult patients with xerostomia (dry mouth). DESIGN: The study was a multicentred, randomized, parallel group, double blind, placebo-controlled clinical trial. SETTING: All examinations and procedures were performed at Tuft's University, Boston, MA, the University of British Columbia, Vancouver, BC or the University of Western Ontario, London, ON. SUBJECTS: Subjects were adults with recent or current dental caries experience, high salivary levels of cariogenic microorganisms and low salivary flow rates. RESULTS: 236 subjects completed at least one post-treatment examination. There were 697 new carious lesions diagnosed, 446 (64%) located on coronal surfaces and 251 (36%) located on root surfaces. The mean attack rate was 0.23 surfaces/100 surfaces at risk. A treatment difference observed between the Active and Placebo groups was statistically significant for root caries increment (p = .02) and total caries increment (p = .03). A treatment difference observed between the Active and Sham groups was not statistically significant for coronal, root or total caries increment. Analysis of variance of treatment group differences was performed using mutans streptococci counts, salivary flow rates, age, sex, caries prevalence, medications, time to first event and early withdrawal as co-variables. These factors did not meaningfully alter the findings. CONCLUSIONS: The difference between the 10% chlorhexidine varnish and placebo treatments is considered to be highly clinically significant for root caries increment (41% reduction) and for total caries increment (25% reduction) but only for coronal caries increment (14%).

Aged↗
PubMed2000

Graphically-enabled integration of bioinformatics tools allowing parallel execution.

Rapid analysis of large amounts of genomic data is of great biological as well as medical interest. This type of analysis will greatly benefit from the ability to rapidly assemble a set of related analysis programs and to exploit the power of parallel computing. TurboGenomics, which is a software package currently in its alpha-testing phase, allows integration of heterogeneous software components to be done graphically. In addition, the tool is capable of making the integrated components run in parallel. To demonstrate these abilities, we use the tool to develop a Web-based application that allows integrated access to a set of large-scale sequence data analysis programs used by a transposon-insertion based yeast genome project. We also contrast the differences in building such an application with and without using the TurboGenomics software.

Computational Biology↗
PubMed1999

Direct, preparative enantioselective chromatography of propranolol hydrochloride and thioridazine hydrochloride using carbon dioxide-based mobile phases.

In this paper, we describe the direct, preparative enantioselective chromatography of racemic (rac)-propranolol hydrochloride (HCI) and rac-thioridazine.HCl using Chiralpak AD chiral stationary phase and mobile phase systems containing carbon dioxide and methanol without the use of basic or acidic additives. Isolated fractions of propranolol.HCl were positively identified by mass spectrometry, Beilstein flame test, melting point, and chemical analysis to be HCI enantiomers of propranolol-HCl salts exhibited characteristic mass spectra peaks at 36 and 38 mass-to-charge ratio in the expected 3:1 isotopic ratio for the solute that were absent in the mass spectra for the free-base forms. To our knowledge, the direct, preparative enantioselective isolation of HCI enantiomeric salts of rac-propranolol and of rac-thioridazine have not been previously demonstrated and published.

Adrenergic beta-Antagonists↗
PubMed1999

Microscopic investigation in fossil hominoidea: a clue to taxonomy, functional anatomy, and the history of diseases.

Ten selected samples of fossilized bones (including Australopithecus, Homo erectus, Homo neandertalensis, and Homo sapiens sapiens) were examined by light microscopy using plane and polarized light. The histomorphological findings show that microscopic research adds much to what can be ascertained by marcoscopic examination or by X-ray techniques. In particular, emphasis was placed on taxonomy, functional anatomy of bones, and causes of some of the diseases of early hominids. Anat Rec (New Anat): 257:225-232, 1999.

Anatomy↗
PubMed1999

Twitch-potentiation increases calcium in peripheral more than in central mitochondria of guinea-pig ventricular myocytes.

1. The mitochondrial total calcium content ([Ca]mt) was studied with electron probe microanalysis (EPMA) in isolated guinea-pig ventricular myocytes in order to answer the question of whether electrical stimulation increases [Ca]mt in subsarcolemmal and central mitochondria to a different extent. 2. In unstimulated myocytes subsarcolemmal [Ca]mt was (mean +/- s.e.m.) 535 +/- 229 micromol (kg dry weight (DW))-1 and central [Ca]mt was 513 +/- 162 micromol (kg DW)-1. These values do not differ and correspond to approximately 180 micromol calcium per litre of mitochondria or 180 microM. 3. Contractions were potentiated to an optimum by stimulation with trains of 12 paired stimuli. After potentiation with 12 paired action potentials, cells were shock-frozen 120 ms after the start of the first action potential of the 13th pair. Subsarcolemmal [Ca]mt was 1.3 +/- 0.4 mmol (kg DW)-1 (433 microM) and central [Ca]mt was 227 +/- 104 micromol (kg DW)-1 (76 microM). The difference was significant. 4. After potentiation with 12 paired voltage-clamp pulses, cells were shock-frozen 120 ms after the start of the first pulse of the 13th pair. Subsarcolemmal [Ca]mt was 2.2 +/- 1.0 mmol (kg DW)-1 (733 microM) and central [Ca]mt was 630 +/- 180 micromol (kg DW)-1 (210 microM). After removal of extracellular K+, five paired voltage-clamp pulses increased subsarcolemmal [Ca]mt to 2.1 +/- 0.8 mmol (kg DW)-1 (700 microM), which was significantly higher than the central [Ca]mt of 389 +/- 88 micromol (kg DW) -1 or 130 microM. 5. In unstimulated cells, [Na] and [K] in subsarcolemmal and central mitochondria were not different. In potentiated myocytes, subsarcolemmal [Na]mt was 236 +/- 20 mmol (kg DW)-1 or 79 mM, which is significantly higher than the central [Na]mt of 50 +/- 5 mmol (kg DW)-1 or 16 mM. 6. The differences in [Ca]mt and [Na]mt are attributed to subsarcolemmal cytosolic microdomains of elevated [Ca2+] and [Na+] generated during contractile potentiation by transmembrane Ca2+ and Na+ fluxes.

Animals↗
PubMed1999

Cytoprotection against lipid hydroperoxides correlates with increased glutathione peroxidase activities, but not selenium uptake from different selenocompounds.

Cells cultivated under standard conditions were highly deficient in tocopherol, selenium, and glutathione peroxidase (GPx) activities. We investigated whether and to what extent the addition of different selenocompounds to growth media would alter biochemical, physiological, and pathophysiological parameters of cultured liver cells. Cellular uptake of selenium, GPx activities, and cytoprotection were measured and compared in human hepatoma cells (HepG2). Selenite and selenocystine were Se donors of high bioavailability (i.e., with these culture supplements, the increased Se uptake, induction of GPx isoenzymes, and protection of treated cells from lipid hydroperoxides were well correlated). In contrast, selenium from selenomethionine was incorporated into cellular proteins but had no effect on GPx activities or cytoprotection. The data show that not all selenium donors provide selenium, which is bioactivated to act as antioxidant. Thus, cellular selenium content, in general, did not correlate with cytoprotective activity of this trace element. However, cellular GPx activities at different times, with different concentrations, and with different Se donors always correlated with protection from lipid hydroperoxides and may, thus, represent a more reliable parameter to define adequate Se supply.

Antioxidants↗
PubMed1999

Merosin-deficient congenital muscular dystrophy associated with abnormal cerebral cortical gyration: an autopsy study.

We report clinical, biopsy and autopsy findings in a merosin-deficient congenital muscular dystrophy (CMD) infant with abnormal cortical gyration. Brain showed polymicrogyria and occipital agyria with marginal neuroglial heterotopia and inferior vermis hypoplasia. There was a normal pattern of myelination consistent with early age. Laminin alpha 2 chain was also absent in myocardium, brain pial-glial membrane, brain and skin blood vessels as well as intramuscular and skin nerves. Occasional basal lamina gaps were found in muscle fibres but not in brain-blood vessels. This is the first autopsy study in a merosin-deficient CMD case with abnormal cortical gyration.

Autopsy↗
PubMed1999

Improvement in Quantitative X-ray Microanalysis of Biological Cryosections.

: The accuracy of Na measurements in biological cryosections has been improved through replacement of the 8 µm Be window of the Si(Li) detector with a Super Atmospheric Thin Window (SuperATW) window mounted on a germanium electron microscope (GEM) detector. Greater accuracy of Ca measurements was also attained when a GEM detector instead of an Si(Li) detector was used for analysis of total Ca concentrations in cardiac muscle. Although the advantage of improved sensitivity for Na and Ca is lost in spot mode analysis because of the overriding contribution of biological variability, this advantage becomes important in X-ray mapping. We compared the two systems by analyzing cryosections of identical biological material under comparable conditions. We found that Si contamination in thin biological cryosections is unpredictable; it may be widespread and differ in degree in various cell compartments of the same cell. Hence, a correction for Si contamination should be included in the calculations of elemental concentrations. We suggest here a procedure for measuring and subtracting Si contamination from elemental spectra.

Journal Article↗
PubMed1999

IL-2-deficient mice raised under germfree conditions develop delayed mild focal intestinal inflammation.

Interleukin-2 (IL-2) amplifies immune stimuli and influences B cell differentiation. IL-2-deficient mice spontaneously develop intestinal inflammation if raised under specific pathogen-free (SPF) conditions. We quantitatively determined the aggressiveness and kinetics of gastrointestinal and hepatic inflammation in the presence or absence of viable bacteria in IL-2-deficient mice. Breeding colonies were maintained under SPF and germfree (GF) conditions. Intestinal tissues, serum, and mesenteric lymph nodes were obtained from mice at different ages for blind histological scoring, immunoglobulin measurements, mucosal T cell infiltration, and cytokine secretion. GF IL-2 -/- mice developed mild, focal, and nonlethal intestinal inflammation with delayed onset, whereas the more aggressive inflammation in SPF IL-2 -/- mice led to their death between 28 and 32 wk. Periportal hepatic inflammation was equal in the presence or absence of bacterial colonization. Intestinal immunoglobulin secretion decreased significantly by 13 wk of age in IL-2 -/- mice in both GF and SPF environments. In contrast to other genetically engineered rodents, IL-2 -/- mice develop mild focal gastrointestinal and active portal tract inflammation in the absence of viable bacteria.

Animals↗
PubMed1999

Docetaxel (Taxotere) as monotherapy in the treatment of hormone-refractory prostate cancer: preliminary results.

Previous chemotherapy trials in hormone refractory prostate cancer have resulted in low response rates and minimal survival impact. Clearly, better agents are needed to improve outcomes in such patients. Microtubule inhibitors have been a recent focus of investigation as chemotherapeutic agents in prostate cancer; in tissue culture, docetaxel (Taxotere; Rhône-Poulenc Rorer, Collegeville, PA) appears to be the most active of these drugs. Patients enrolled in this trial had hormone refractory prostate cancer and were required to have progressive disease despite hormonal therapy and, if previously treated with antiandrogens, have progressive disease despite antiandrogen withdrawal. Patients had not been exposed to any prior chemotherapy. Testosterone suppression was continued during the trial when patients received docetaxel at 75 mg/m2 every 21 days. Thirty-five patients with ages ranging from 49 to 85 years (median age, 70 years) were enrolled in the trial. Three hundred twelve treatments have been given (median, six treatments), with a minimum follow-up of 4 months. The median prostate-specific antigen (PSA) at the time of entry was 96 ng/mL (range, 24 to 2,070 ng/mL). Seven patients (20%) have had a more than 80% decline in PSA and 16 (46%) have had a more than 50% decline. Six additional patients have had a PSA decline of 40% to 50%. Soft tissue disease was seen in 25 of 35 patients. One patient had a complete response; three others had a nearly complete response. Three patients met criteria for a partial response, yielding a 28% response rate with measurable disease. Three additional patients had substantial shrinkage and 12 had prolonged stable disease. Combining both PSA and soft tissue responses, one complete response and five partial responses were seen. Substantial responses, defined as a more than 40% PSA decline and a more than 50% reduction of bidimensional cross-products in patients with measurable disease, were seen in 17 of 35 patients enrolled. Responses were maintained for a median of 9 months (range, 2 to 24 months). The median overall survival was 27 months. Three patients remain under therapy. Toxicity remained tolerable throughout the treatment. Grade 4 toxicities requiring discontinuation of treatment included stomatitis, small bowel obstruction, and a gluteal abscess. There were two deaths during the study: one due to lung toxicity/pneumonia and one due to pulmonary embolus. The patient with lung toxicity had markedly elevated transaminases with marked involvement of the liver with tumor. Six patients stopped voluntarily due to fatigue or edema Other common toxicities were neutropenia, anemia, mild edema and hyperglycemia (due to steroids), anorexia, myalgias, and mild alopecia The responses seen in this population are very encouraging and suggest substantial durable activity for docetaxel as single-agent therapy for hormone refractory prostate cancer.

Aged↗
PubMed1998

Increased expression of DNA-dependent protein kinase confers resistance to adriamycin.

Acquired resistance to adriamycin (ADR) in an HL60 cell line is shown to be accompanied by an increase in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) at both the protein and mRNA levels (15-20-fold) and an overall 3-fold increase in DNA-PK enzyme activity. The other components of the DNA-PK Ku autoantigen complex, Ku70 and Ku80, were 3-fold increased and unchanged, respectively. Time dependent repair of ADR-induced DNA damage was measured by the neutral comet assay and found to be more efficient in the drug resistant cell line (HL60/ADR). Antisense RNA transfection reduced the protein expression of DNA-PKcs to 50% in HL60/ADR and partially reversed drug resistance. A fibroblast cell line from a severe combined immunodeficient (SCID) mouse was deficient in functional DNA-PKcs and showed increased sensitivity to ADR and other DNA damaging agents compared to wild type. These studies demonstrate that alteration in DNA-PK can contribute to chronic stress response leading to acquired drug resistance. The overexpression of DNA-PK is thus shown to be a novel cellular adaptation mechanistically contributing to the resistance of cancer cells to the anthracycline drug adriamycin, and as such, may have implications for its therapeutic use.

Adaptation, Physiological↗
PubMed1998

Bolus thrombolytic infusions during CPR for patients with refractory arrest rhythms: outcome of a case series.

Thrombolytic therapy has been accepted in the treatment of acute myocardial infarction. Given historical recommendations that thrombolytic therapy is contraindicated in patients receiving CPR, its potential clinical benefit for facilitating conversion of rhythm in patients in refractory cardiac arrest has not been investigated. We present three case reports in which patients with confirmed acute myocardial infarction had a witnessed cardiac arrest in the ED. Standard Advanced Cardiac Life Support measures failed in all three cases. A bolus infusion of tissue plasminogen activator was administered during CPR in refractory ventricular fibrillation (two cases) and pulseless ventricular tachycardia (one case). Patients were given tissue plasminogen activator and had defibrillation, followed by a spontaneous return of circulation, with resuscitation and subsequent discharge. No postarrest sequelae were observed as a result of thrombolytic use during the resuscitative process. We conclude that bolus thrombolytic infusions during CPR may facilitate spontaneous return of circulation in select patients with confirmed acute myocardial infarction, witnessed cardiac arrest in the ED, and refractory ventricular fibrillation or tachycardia.

Adult↗
PubMed1998

Improved quantitative electron probe X-ray microanalysis of biological cryosections using an EDS germanium detector and a super-atmosphere thin window (SuperATW).

A new Link energy-dispersive GEM detector with SuperATW window was tested for quantitative electron probe microanalysis of low calcium and sodium concentrations ([Ca], [Na]) in intracellular compartments of cardiac myocytes. We compare Ca profiles with high count statistics and similar peak area collected under the same conditions with either a Be-windowed Si and a Ge SuperATW detector. The height of the Ca peak was increased by 7%, the full width at half-maximum height was reduced by 9% with the Ge detector. The counts statistics of the Ca K alpha peak improved by 9% and the partial overlap with the K K beta peak was better deconvoluted. We calculate [Ca] and errors of the single measurement in mitochondria of guinea-pig cardiac myocytes from spectra acquired with a Si or Ge detector. For identical analysis conditions, the [Ca] were identical; however, with the Ge SuperATW detector, the calculated error of the single measurement was only 1/2.7 of that calculated from measurements with the Si detector. We compare the peak area of identical [Na] in spectra collected with the Be-windowed Si detector and Ge SuperATW detector. The peak area was significantly higher with the SuperATW Ge than with the Si detector and Be window, whereas the continuum in the range 4-10 keV was comparable, demonstrating the improved sensitivity for low atomic elements such as Na of the Ge SuperATW detector. [Na] and errors of the single measurement in mitochondria of quiescent guinea-pig cardiac myocytes were calculated from spectra acquired with the Si or the Ge detector. The use of the Ge SuperATW detector improved the detectability limit for sodium by more than 80% and reduced the error of the single measurement by a factor of 7-8.

Animals↗
PubMed1998

Pathological bone changes in the mandibles of wild red deer (Cervus elaphus L.) exposed to high environmental levels of fluoride.

A macroscopic, microscopic and scanning electron microscope study was performed on the pathological bone changes of the mandibles of wild red deer (n = 61) exhibiting severe dental fluorosis. The animals originated from a highly fluoride polluted area in Central Europe (Ore mountains and their southern foreland, Czech-German border region) and constituted 11.2 % of the studied red deer sample (n = 545) from this area. Pathologically increased wear and fracture of fluorosed teeth caused a variety of mandibular bone alterations, including periodontal breakdown, periostitis, osteitis and chronic osteomyelitis. As a further consequence of severe dental attrition, opening of the pulp chamber and formation of periapical abscesses were occasionally observed. In case of severe periodontal breakdown, loss of teeth from the mandibles was found. In addition to the inflammatory bone changes, the occurrence of osteofluorotic alterations was also diagnosed in the specimens with the highest bone fluoride concentrations (> 4000 mg F-/kg dry wt). These changes comprised extended apposition of periosteal bone onto the mandibular cortex as well as deformation of the mandibular body, which was attributed to a fluoride-induced osteomalacia. The present study provided circumstantial evidence that, in addition to fluoride induced dental lesions, the occurrence of marked periodontal disease and tooth loss is an important factor responsible for a reduction of life expectancy in severely fluorotic wild red deer.

Animals↗
PubMed1998

Measurement of oxygen production by in vitro human and animal lenses with an oxygen electrode.

PURPOSE: This paper describes an advantageous method of measuring the activity of the enzyme catalase, which has an important antioxidative role in the lens. This method allows the measurement of catalase in whole lenses. METHODS: Exposure to UVA (99% UV-A) radiation was used to stress animal and human (Eye Bank) lenses in vitro. The ability of lens catalase to convert H2O2 into O2 was measured directly, using an oxygen electrode and meter. This method is very specific, as catalase is the only enzyme that converts H2O2 to O2. RESULTS: Catalase in the lenses of humans, rabbits, and squirrels catalyzed the production of O2 from H2O2 very efficiently. The anterior equatorial regions of these lenses were the most active O2 producing areas. More than 95% of lens catalase activity was found in the capsule-epithelium layer. Exposure to UVA radiation, up to approximately 100 J/cm2 in 18 h, strongly inhibited O2 production from 0.77 mM H2O2 by the lenses. Catalase activity decreased with increasing age. Mixed cataractous human lenses produced O2 from H2O2 at only 60% of the rate of normal lenses of similar ages. Nuclear cataracts produced O2 at only 75% of the rate of normal lenses. Alpha-tocopherol (10(-5) M) protected lens catalase activity strongly. Alpha-tocopherol is known to accumulate in and protect against cell membrane peroxidation, and against singlet oxygen formation. These oxidative mechanisms appear to contribute to catalase photoinactivation. CONCLUSIONS: The method described indicated that catalase is a crucial antioxidative enzyme in the normal lens. Its inactivation could upset the oxidation-reduction balance in the lens and stimulate lens opacification.

Adult↗
PubMed1998

Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice.

Mice with targeted deletion of the gene for interleukin-10 (IL-10) spontaneously develop enterocolitis when maintained in conventional conditions but develop only colitis when kept in specific-pathogen-free (SPF) environments. This study tested the hypothesis that enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice. IL-10-deficient mice were maintained in either SPF conditions or germfree conditions or were populated with bacteria known to cause colitis in other rodent models. IL-10-deficient mice kept in SPF conditions developed colitis in all segments of the colon (cecum and proximal and distal colon). These mice exhibited immune system activation as evidenced by increased expression of CD44 on CD4(+) T cells; increased mesenteric lymph node cell numbers; and increased production of immunoglobulin A (IgA), IgG1, and IL-12 p40 from colon fragment cultures. Mice populated with bacterial strains, including Bacteroides vulgatus, known to induce colitis in other rodent models had minimal colitis. Germfree IL-10-deficient mice had no evidence of colitis or immune system activation. We conclude therefore that resident enteric bacteria are necessary for the development of spontaneous colitis and immune system activation in IL-10-deficient mice.

Animals↗