Biomedical subjects

I Magnusson

Publications and source records attributed to I Magnusson.

At least 55 records · Page 3Linked to original sources

PubMed1993

Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma.

An impaired immune response is frequently observed in cancer patients and tumor-bearing mice. T-cells from mice with an experimental colon carcinoma were recently shown to express T-cell receptors that completely lacked the signal-transducing molecule CD3 zeta. Here, we have investigated the expression of the signal-transducing molecule zeta on lymphocytes from 14 patients with colorectal carcinomas using flow cytometric analysis of permeabilized cells with a monoclonal antibody (TIA-2; IgG1) specific for the cytoplasmic domain of the zeta chain as well as with immunoprecipitation and analysis on diagonal gel electrophoresis. We demonstrate that T-cells isolated from the tumors of the patients express significantly less CD3 zeta than T-cells in the peripheral blood of the same patients and that the peripheral blood of the patients express decreased levels of zeta chains, as compared to the levels found in lymphocytes from healthy controls. This decreased expression was also observed on zeta chains associated with the low affinity Fc receptor for IgG found in tumor-infiltrating NK cells (Fc gamma RIIIA alpha; CD16).

Colorectal Neoplasms↗

PubMed1993

Effect of monoclonal antibody 17-1A and GM-CSF in patients with advanced colorectal carcinoma--long-lasting, complete remissions can be induced.

Antibody-dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of unconjugated monoclonal antibodies (MAbs) in tumor therapy. The antitumor activity of MAbs might therefore be augmented if the cytotoxic capability of the effector cells could be increased. In an in vitro system, the killing capacity of MAb was significantly enhanced by pre-treatment of the effector cells with granulocyte-macrophage colony-stimulating factor (GM-CSF). Based on these findings, the therapeutic effect of the combination of mouse MAb 17-1A (IgG2a) and GM-CSF was evaluated in 20 patients with metastatic colorectal carcinoma (CRC). The patients received GM-CSF for 10 days and a single i.v. infusion of MAb 17-1A on day 3 of the cycle. Four cycles were given at 1-monthly intervals. There was a continuous increase in blood monocytes and lymphocytes during all 4 GM-CSF cycles. Neutrophils and eosinophils were also significantly augmented but in a biphasic manner and the cell counts on day 10 of cycle IV were significantly lower than in cycles I and II. GM-CSF-related side-effects were of no major clinical importance. During the third cycle, an immediate-type allergic reaction (ITAR) against MAb 17-1A occurred in most patients, necessitating reduction of the MAb dose as well as of the infusion rate. Two patients achieved complete remission. One patient had a minor response, and 3 other patients were considered to have stable disease > 3 months.

Adolescent↗

PubMed1993

The therapeutic use of the unconjugated monoclonal antibodies (MAb) 17-1A in combination with GM-CSF in the treatment of colorectal carcinoma (CRC).

Unconjugated monoclonal antibodies (MAb) and granulocyte macrophage-colony stimulating factor (GM-CSF) may induce tumor regression in patients. Antibody-dependent cellular cytotoxicity (ADCC) is considered to be one of the effector functions of MAb. Human peripheral blood mononuclear cells (PBMC) preincubated with GM-CSF and used as effector cells in an 18h ADCC assay with SW948 (human colorectal carcinoma cell line) as target cells and MAb 17-1A induced significant increase in the lytic capacity of the effector cells. Based on these findings the therapeutic effect of the combination of mouse MAb 17-1A (IgG2a) against colorectal carcinoma (CRC) cells and GM-CSF was evaluated in 20 patients with metastatic CRC. The patients received GM-CSF (250 micrograms/m2/day s.c.) for 10 days and a single i.v. infusion of MAb 17-1A (400 mg) at day 3 of the cycle. The cycles were repeated with an interval of one month. Four cycles were given. ADCC as well as Fc-receptor bearing mononuclear cells increased significantly during therapy. Two patients achieved CR (10%). One patient had an MR (5%) and a further three patients were considered to have SD > 3 months (15%). The two CR patients are still in CR, 35+ and 30+ months respectively after initiation of therapy. Patients with an ADCC activity at start of therapy above the median value of the total patient material survived significantly longer than those patients with an ADCC reactivity below this value (p = 0.002).

Adolescent↗

PubMed1993

Evaluation of reliability and reproducibility of dental indices.

Evaluation of periodontal therapy involves the use of several oral indices to describe the health status of hard and soft tissues. It was the objective of the present study to evaluate the reliability and reproducibility of some of these indices. A calibration and standardization session was designed to calibrate 10 examiners and a "gold standard" (an experienced examiner) in evaluating the following indices: the Volpe-Manhold calculus index (VM), the Lobene stain index (SI), a non-invasive modification of the Löe-Silness gingival index (GI), the papillary bleeding score (PBS) of Loesche, and the plaque index (PI) of Quigley-Hein as modified by Turesky. For each index, the average intraclass correlation was calculated between two subject visits. The highest intraclass correlation, 0.94, was found for PBS. The intraclass correlation for PI was 0.70 and for VM, 0.65. The lowest intraclass correlations were for stain, 0.47, and GI, 0.25. Intra-subject correlations between the 2 visits were good for all indices, but were best for PBS, followed by VM. PBS seems to be the most reliable index (both intra- and inter-examiner) for measuring the oral health status and is therefore recommended for use in clinical studies.

Analysis of Variance↗

PubMed1993

Change detection on longitudinal data in periodontal research.

Longitudinal data of attachment level (AL) or the alveolar bone level are often used to assess the progression of periodontal disease. This paper tries to identify the most efficient method to detect the changes of AL in a general periodontal research environment; that is, a sequential decision based on multiple sites. Several existing methods suggested in the periodontal research literature such as the tolerance, running median, cusum, and regression methods as well as change-point detection methods in the statistical literature are examined. It is found that the regression method is most convenient among the several methods that are equally effective in change detection. Formulae, tables and their usage are discussed in detail.

Decision Support Techniques↗

PubMed1993

14C-labeled propionate metabolism in vivo and estimates of hepatic gluconeogenesis relative to Krebs cycle flux.

Purposes of this study were 1) to estimate in humans, using 14C-labeled propionate, the rate of hepatic gluconeogenesis relative to the rate of Krebs cycle flux; 2) to compare those rates with estimates previously made using [3-14C]lactate and [2-14C]acetate; 3) to determine if the amount of ATP required for that rate of gluconeogenesis could be generated in liver, calculated from that rate of Krebs cycle flux and splanchnic balance measurements, previously made, and 4) to test whether hepatic succinyl-CoA is channeled during its metabolism through the Krebs cycle. [2-14C]propionate, [3-14C]-propionate, and [2,3-14C]succinate were given along with phenyl acetate to normal subjects, fasted 60 h. Distributions of 14C were determined in the carbons of blood glucose and of glutamate from excreted phenylacetylglutamine. Corrections to the distributions for 14CO2 fixation were made from the specific activities of urinary urea and the specific activities in glucose, glutamate, and urea previously found on administering [14C]-bicarbonate. Uncertainties in the corrections and in the contributions of pyruvate and Cori cyclings limit the quantitations. The rate of gluconeogenesis appears to be two or more times the rate of Krebs cycle flux and pyruvate's decarboxylation to acetyl-CoA, metabolized in the cycle, less than one-twenty-fifth the rate of its decarboxylation. Such estimates were previously made using [3-14C]lactate. The findings support the use of phenyl acetate to sample hepatic alpha-ketoglutarate. Ratios of specific activities of glucose to glutamate and glucose to urinary urea and expired CO2 indicate succinate's extensive metabolism when presented in trace amounts to liver. Utilizations of the labeled compounds by liver relative to other tissues were in the order succinate = lactate > propionate > acetate. ATP required for gluconeogenesis and urea formation was approximately 40% of the amount of ATP generated in liver. There was no channeling of succinyl-CoA in the Krebs cycle in the hepatic mitochondria.

Adult↗

PubMed1993

The strategy and advantage in use of an electronic probe for attachment measurement.

Attachment level has been used as the "gold standard" for assessment of the progression of periodontal disease. However, the measurement of attachment level by periodontal probing can be subject to a large number of error sources. Recently, we have designed experiments by using an electronic probe to identify the magnitude of error components due to the instrument, gingival tissue condition, position or probing angle, and time interval between replicate probings. Even with a very careful clinical setting, a few percent of uncontrollable large errors or outliers could not be avoided. A previously used 'option-3' probing scheme to reduce the unexpected large error is justified from the mathematical viewpoint.

Analysis of Variance↗

PubMed1993

A role for antibiotics in the treatment of refractory periodontitis.

Refractory periodontitis is considered by many investigators to be a separate disease entity that is descriptive of a particular patient who has multiple sites, rather than a few individual sites, that do not respond to conventional periodontal treatment modalities. Such patients continue to demonstrate loss of attachment and alveolar bone despite frequent periodontal treatment which includes surgical intervention, scaling and root planing, and often systemically-administered tetracycline. Controlled clinical studies have demonstrated that both clindamycin-hydrochloride and amoxicillin/clavulanate potassium (Au) are beneficial when used in conjunction with periodontal scaling. Gordon et al. found improvements in attachment levels, inflammation, suppuration, and a decrease in pocket depths for up to 2 years following a 7-day course of clindamycin given in conjunction with a full-mouth scaling. The incidence of disease activity decreased from an annual rate of 8% of all sites prior to antibiotic treatment to 0.5% after treatment. Magnusson, reporting on a similar group treated with a 14-day course of Au, found an average loss of attachment of 2.2 mm and an increase in pocket depth of 1.5 mm in sites demonstrating disease progression prior to antibiotic treatment. At 3 months post-antibiotic therapy, these sites had regained an average of 2 mm of attachment and pocket depths had decreased an equivalent amount. Both attachment levels and pocket depths remained relatively stable for up to 12 months post-therapy. In an ongoing study, 30 subjects with refractory periodontitis were treated with either clindamycin or Au in conjunction with scaling or scaling plus a placebo. Prior to antibiotic treatment, but while being scaled at 3-month intervals, sites with disease activity lost an average 2.4 mm of attachment. At 3 months post-treatment, the clindamycin-treated group showed an average gain of 2.1 mm, the Au-treated group gained 1.9 mm, and the scaling group gained 1.4 mm in attachment. The clindamycin group remained relatively stable for up to 21 months and the Au group remained stable for about 15 months without additional treatment. Five of the 6 subjects treated with scaling alone required additional treatment within 9 months. Preliminary analyses have indicated that at least two patterns or rates of attachment loss may be associated with refractory periodontitis and that each pattern may be indicative of a different microflora. The pattern associated with a relatively rapid loss of attachment was characterized by a Gram-negative flora which contained spirochetes, P. intermedia, and Fusobacterium species.(ABSTRACT TRUNCATED AT 400 WORDS)

Anti-Bacterial Agents↗

PubMed1992

The use of non-invasive probes and (13)C nuclear magnetic resonance spectroscopy to assess liver metabolism in humans.

Two new methods to assess liver metabolism in humans will be discussed, non-invasive probes and (13)C NMR (nuclear magnetic resonance) spectroscopy. Hepatic UDP-glucose and alpha-ketoglutarate can be sampled by non-invasive probes. This method has been used to quantitate the contribution of the indirect pathway to liver glycogen formation and to estimate relative flow rates and carbon exchange in the Krebs cycle. (13)C NMR spectroscopy has been developed to measure liver glycogen concentrations in vivo. Using this method in combination with measurements of whole body glucose production during fasting, the contribution of gluconeogenesis has been calculated.

Journal Article↗

PubMed1992

Predictive power of various models for longitudinal attachment level change.

Several statistical models that have been suggested in the periodontal literature for describing longitudinal attachment level changes, such as the gradual loss, single-burst, multiple-burst, and random walk models as well as other models introduced in this paper are compared by their power to predict future attachment loss. The data used in this analysis is from 1061 sites of 8 subjects, with moderate to severe periodontal disease, monitored monthly for about a year. This study found that none of the suggested models could significantly outperform the naïve mean predictor, which predicts the future attachment level from the past mean. It was also found that no single model, such as the burst, gradual, or random walk, together with measurement error can fully explain the variation in the data. These results indicate that in the course of one year, the attachment level change may not follow the same model. Consequently, a model that fits well to past data cannot be accurately extended to the future.

Disease Susceptibility↗

PubMed1992

Reproducibility of an electronic probe in relative attachment level measurements.

4 probing designs have been employed to investigate the reproducibility of the Florida Probe. 3 groups (each composed of 10 subjects) were selected for the study: healthy adults, gingivitis subjects, and periodontitis subjects. The 4 probing designs were as follows: (a) the probe tip was left in the sulcus between successive probings; (b) the probe tip was removed from the gingival margin between probings but the next probing followed immediately; (c) successive whole-mouth probings were interrupted by a 5-min interval and a mouthrinse; (d) there was a 4-week interval between each probing. 3 measurements were taken for each design. The main purpose of this study was to identify variance components in the attachment level variation. The maximum probing error standard deviation was found to be around 0.3 mm, which is considerably smaller than that found in most previous studies. The errors associated with the periodontal condition and probing effect were also estimated. The variance components obtained here can be used for determining the sample size in controlled clinical studies.

Adult↗

PubMed1992

The effect of 3 mouthrinses on plaque and gingivitis development.

The aim of this study was to evaluate the effect of 3 mouthrinses, Listerine Antiseptic (thymol), Peridex (chlorhexidine), Perimed (povidone iodine and hydrogen peroxide), and a placebo (water) on the development of dental plaque and gingivitis, when used as the only oral hygiene procedure for 14 days. 71 subjects were entered into a randomized, double-blind study. At the baseline examination, papillary bleeding score (PBS), and plaque index (PI) were registered, after which subjects received supragingival prophylaxis and were assigned to 1 of 4 study cells. Subjects were asked to refrain from all oral hygiene procedures except for the supervised 14-day 2 x daily rinsing with the assigned preparation. At day 14, the same clinical parameters were again registered. Statistical analysis was performed by a one-way analysis of variance (ANOVA) to compare the 4 groups, followed by Duncan's multiple range test to determine specific group differences. At baseline, average PBS and PI scores were similar for all 4 groups. After 14 days, the average PBS for Peridex and Perimed was significantly lower than for Listerine Antiseptic and water. The frequency of interdental units with a PBS greater than 2 was significantly lower for Peridex and Perimed than for Listerine Antiseptic and water. We concluded that both Peridex and Perimed were effective in reducing plaque and gingivitis when used as a 2 x daily mouthrinse by subjects refraining from other oral hygiene procedures. In vitro, a synergistic effect was assumed when inhibition was achieved with Perimed at the same or greater dilution than was achieved with povidone-iodine alone.

Actinomyces viscosus↗

PubMed1992

Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study.

UNLABELLED: To quantitate hepatic glycogenolysis, liver glycogen concentration was measured with 13C nuclear magnetic resonance spectroscopy in seven type II diabetic and five control subjects during 23 h of fasting. Net hepatic glycogenolysis was calculated by multiplying the rate of glycogen breakdown by the liver volume, determined from magnetic resonance images. Gluconeogenesis was calculated by subtracting the rate of hepatic glycogenolysis from the whole body glucose production rate, measured using [6-3H]glucose. Liver glycogen concentration 4 h after a meal was lower in the diabetics than in the controls; 131 +/- 20 versus 282 +/- 60 mmol/liter liver (P < 0.05). Net hepatic glycogenolysis was decreased in the diabetics, 1.3 +/- 0.2 as compared to 2.8 +/- 0.7 mumol/(kg body wt x min) in the controls (P < 0.05). Whole body glucose production was increased in the diabetics as compared to the controls, 11.1 +/- 0.6 versus 8.9 +/- 0.5 mumol/(kg body wt x min) (P < 0.05). Gluconeogenesis was consequently increased in the diabetics, 9.8 +/- 0.7 as compared to 6.1 +/- 0.5 mumol/(kg body wt x min) in the controls (P < 0.01), and accounted for 88 +/- 2% of total glucose production as compared with 70 +/- 6% in the controls (P < 0.05). IN CONCLUSION: increased gluconeogenesis is responsible for the increased whole body glucose production in type II diabetes mellitus after an overnight fast.

Aged↗

PubMed1992

Measuring clinical attachment: reproducibility of relative measurements with an electronic probe.

During the past few years, improvements in detecting longitudinal changes in clinical attachment or alveolar bone density have been introduced. For example, constant-force electronic probes and computer-assisted subtraction analysis of longitudinal radiographs have been reported to be more sensitive and reproducible in detecting changes in clinical attachment or alveolar bone density, respectively. Use of these new technologies requires that sources of measurement error be identified and their contribution quantified. This study investigated the reproducibility of a constant-force electronic probe in a careful clinical setting. Measurements were performed from individually fabricated acrylic stents. Three groups of subjects were selected for the study: 10 adults without oral disease, 10 adults with gingivitis, and 10 adults with moderate periodontitis. Four probing designs were employed to investigate the reproducibility of the probe. In design A, the probe tip was left in the sulcus between successive probings. In design B, the probe tip was removed from the gingival margin between probings but the next probing followed immediately. In design C, successive whole-mouth probings were interrupted by a 5-minute interval and a mouth rinse. In design D there was a 4-week interval between each successive probing. Three measurements were taken at each site for each design. The main purpose of this study was to identify variance components in the attachment level variation. The maximum probing error standard deviation ranged from 0.2 to 0.3 mm depending on the periodontal health of the subject. This level of variation is considerably smaller than that found in most previous studies.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1991

Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR.

The rate of net hepatic glycogenolysis was assessed in humans by serially measuring hepatic glycogen concentration at 3- to 12-hour intervals during a 68-hour fast with 13C nuclear magnetic resonance spectroscopy. The net rate of gluconeogenesis was calculated by subtracting the rate of net hepatic glycogenolysis from the rate of glucose production in the whole body measured with tritiated glucose. Gluconeogenesis accounted for 64 +/- 5% (mean +/- standard error of the mean) of total glucose production during the first 22 hours of fasting. In the subsequent 14-hour and 18-hour periods of the fast, gluconeogenesis accounted for 82 +/- 5% and 96 +/- 1% of total glucose production, respectively. These data show that gluconeogenesis accounts for a substantial fraction of total glucose production even during the first 22 hours of a fast in humans.

Adult↗

PubMed1991

Noninvasive tracing of Krebs cycle metabolism in liver.

To quantify intrahepatic Krebs cycle metabolism, phenyl acetate, excreted in urine as a glutamine conjugate, was given to healthy subjects infused with [3-14C]lactate. They were studied after 60 h of fasting and when given glucose after an overnight fast. Distributions of 14C in glutamate from urinary phenylacetylglutamine and blood glucose were determined. Corrections to the distributions because of the fixation of 14CO2 formed from the [3-14C]lactate were determined by administering [14C]bicarbonate. Comparisons of distributions in glucose and glutamate support the assumption that the glutamate distributions reflect those in hepatic alpha-ketoglutarate. From the distributions in glutamate, the extent of exchange of labeled with unlabeled carbons and relative flow rates in the cycle in liver were estimated. Dilution of 14C by 12C in the cycle was found in the fasted but not the fed state. In the fasted state, pyruvate carboxylation was estimated to be at least twice the rate of Krebs cycle flux and the rate of pyruvate's decarboxylation less than 1/25 the rate of its carboxylation. In the fed state, the rate of decarboxylation was estimated to be between one-sixth and one-half the rate of carboxylation. The rate of conversion of oxalacetate to fumarate in both states appeared to be greater than 6 times the rate of Krebs cycle flux.

Adult↗

PubMed1991

Metabolism of [2-14C]acetate and its use in assessing hepatic Krebs cycle activity and gluconeogenesis.

To examine the fate of the carbons of acetate and to evaluate the usefulness of labeled acetate in assessing intrahepatic metabolic processes during gluconeogenesis, [2-14C]acetate, [2-14C]ethanol, and [1-14C]ethanol were infused into normal subjects fasted 60 h and given phenyl acetate. Distributions of 14C in the carbons of blood glucose and glutamate from urinary phenylacetylglutamine were determined. With [2-14C]acetate and [2-14C]ethanol, carbon 1 of glucose had about twice as much 14C as carbon 3. Carbon 2 of glutamate had about twice as much 14C as carbon 1 and one-half to one-third as much as carbon 4. There was only a small amount in carbon 5. These distributions are incompatible with the metabolism of [2-14C]acetate being primarily in liver. Therefore, [2-14C]acetate cannot be used to study Krebs cycle metabolism in liver and in relationship to gluconeogenesis, as has been done. The distributions can be explained by: (a) fixation of 14CO2 from [2-14C]acetate in the formation of the 14C-labeled glucose and glutamate in liver and (b) the formation of 14C-labeled glutamate in a second site, proposed to be muscle. [1,3-14C]Acetone formation from the [2-14C]acetate does not contribute to the distributions, as evidenced by the absence of 14C in carbons 2-4 of glutamate after [1-14C]ethanol administration.

Acetates↗

PubMed1991

Evaluation of statistical methods for monitoring periodontal disease.

Three methods for detecting the progression of periodontal disease based on the change in attachment level on teeth are compared from a statistical point of view. Regardless of gradual or burst disease progression theories, the regression method is found to be the most efficient way to detect changes. The exact false alarm rate is computed when the decision is based on the maximum regression coefficient at all sites during several visits.

Epithelial Attachment↗