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Biomedical subjects

F Lindgren

Publications and source records attributed to F Lindgren.

At least 19 recordsLinked to original sources
PubMed2000

Statistical molecular design of building blocks for combinatorial chemistry.

The reduction of the size of a combinatorial library can be made in two ways, either base the selection on the building blocks (BB's) or base it on the full set of virtually constructed products. In this paper we have investigated the effects of applying statistical designs to BB sets compared to selections based on the final products. The two sets of BB's and the virtually constructed library were described by structural parameters, and the correlation between the two characterizations was investigated. Three different selection approaches were used both for the BB sets and for the products. In the first two the selection algorithms were applied directly to the data sets (D-optimal design and space-filling design), while for the third a cluster analysis preceded the selection (cluster-based design). The selections were compared using visual inspection, the Tanimoto coefficient, the Euclidean distance, the condition number, and the determinant of the resulting data matrix. No difference in efficiency was found between selections made in the BB space and in the product space. However, it is of critical importance to investigate the BB space carefully and to select an appropriate number of BB's to result in an adequate diversity. An example from the pharmaceutical industry is then presented, where selection via BB's was made using a cluster-based design.

Algorithms↗
PubMed1998

[Measuring corneal thickness in photo-keratectomy with a reflectometry incorporated into the laser beam of the excimer laser].

PURPOSE: To integrate a newly developed OLCR instrument into the optical system of the excimer laser. The instrument is designed to perform corneal pachymetry before, during, and after corneal photoablation and thus allow for a precise and continuous on-line measurement of the corneal photoablation process. METHODS: The conditions required to integrate the OLCR instrument into the excimer laser optics were investigated. With a technical setting providing on-line data of corneal thickness, three groups of 8-10 corneae received central keratectomies of 27 (group 1), 82 (group 2) and 163 (group 3) microns calculated central depth and 7.38 mm diameter. All measurements were performed with OLCR and ultrasound. RESULTS: The OLCR instrument was coupled into the optical system of the excimer laser and a useful signal obtained at SLD power levels of 40 microW incident on the cornea. Individual corneal thickness measurements were obtained before, during and after the photoablation procedure. In group 1, the ablation was 50.3 (40-68) microns measured with ultrasound and 30.2 (27-38) microns measured with OLCR. In group 2, the ablation was 101.1 (80-113) microns measured with ultrasound and 93.3 (76-109) microns measured with OLCR. In group 3, the ablation was 210.6 (190-227) microns measured with ultrasound and 188.4 (181-197) microns measured with OLCR. The precision (standard deviation) for measurements of individual corneas was 1-2 microns with OLCR and up to 12 mm in Ultrasound measurements. CONCLUSION: With this interferometric method, continuous, non-contact measurement of corneal thickness before, during and after excimer laser photoablation were performed. By establishing a feed-back control between the pachymetric measurements and the photoablation process, the precision of excimer ablation may possibly be further increased.

Animals↗
PubMed1997

Toxicity in vitro of some silicon carbides and silicon nitrides: whiskers and powders.

The objectives of this work were to investigate the toxicity of silicon carbide whiskers and powders and silicon nitride whiskers and powders and to compare their toxicity with the toxicity of crocidolite. The effects studied were inhibition of the cloning efficiency of V79 cells, formation of DNA strand breaks by means of a nick translation assay, formation of oxygen radicals in three different assays, and the ability to stimulate neutrophils to produce hydroxyl radicals. All materials showed concentration-dependent inhibition of the cloning efficiency of V79 cells. The inhibition by the most toxic whiskers was in the same order of magnitude as that of crocidolite. Milled whiskers and powders were less toxic than the whiskers. There was a high DNA breaking potential for crocidolite and four of the silicon carbide whiskers and a rather low one for the other materials. Formation of hydroxyl radicals was found for crocidolite and one of the silicon carbide whiskers. In the neutrophil activation test, there was a great variation in the different materials' abilities to activate neutrophils. There was also a good correlation between chemiluminescence and H2O2 formation. The highest activation was found in neutrophils exposed to two of the silicon carbide whiskers and one milled whisker. The conclusion of the investigation is that some of the ceramic materials studied had damaging biological effects comparable to or greater than those of crocidolite. The results from the investigation clearly imply that caution is needed in the introduction of new ceramic fiber materials, so that the correct precautions and protective devices are used in order to avoid harm to the personnel handling the material.

Air Pollutants, Occupational↗
PubMed1996

Modelling of the biological activity for a set of ceramic fibre materials: a QSAR study.

The objective was to develop quantitative structure-activity relationships (QSARs) for a set of nine ceramic raw materials. The samples were characterized by a chemical analysis (both X-ray fluorescence and neutron activation analysis) and the morphology was determined by electron microscopy in combination with automated image analysis. Further, the fibre samples were subjected to two biological activity assays, measuring cytotoxicity and hydroxyl radical production. To investigate the produced data structures, principal component analysis (PCA) and partial least squares (PLS) were applied together with rigorous validation techniques. Significant QSARs were found for both biological activity assays. The morphology of the fibres plays an important role for the cytotoxicity and their trace element background is related to the hydroxyl radical production.

Animals↗
PubMed1991

Minimum analogue peptide sets (MAPS) for quantitative structure-activity relationships.

The information contents in previously published peptide sets was compared with smaller sets of peptides selected according to statistical designs. It was found that minimum analogue peptide sets (MAPS) constructed by factorial or fractional factorial designs in physiochemical properties contained substantial structure-activity information. Although five to six times smaller than the originally published peptide sets the MAPS resulted in QSAR models able to predict biological activity. The QSARs derived from a MAPS of nine dipeptides, and from a set of 58 dipeptides inhibiting angiotensin converting enzyme were compared and found to be of equal strength. Furthermore, for a set of bitter tasting dipeptides it was found that an incomplete MAPS of 10 dipeptides gave just as good a model as the model based on a set of 48 dipeptides. By comparison other non-designed sets of peptides gave QSARs with poor predictive power. It was also demonstrated how MAPS centered on a lead peptide can be constructed as to specifically explore the physiochemical and biological properties in the vicinity of the lead. It was concluded that small information-rich peptide sets MAPS can be constructed on the basis of statistical designs with principal properties of amino acids as design variables.

Amino Acid Sequence↗
PubMed1991

The influence of eye colour on susceptibility to TTS in humans.

In order to investigate the function of the inner ear melanin, noise-induced temporary hearing loss (temporary threshold shift, TTS) was studied in humans with either blue or brown iris colour. Sixty-eight normally hearing teenage boys participated in this study. Hearing thresholds before and after exposure were established with a computerized sweep frequency audiometer in the frequency range 0.8-8 kHz. The noise exposure consisted of a 1/3 octave band-filtered noise with centre frequency 2 kHz at 105 dB SPL for 10 min. The mean TTS in the frequency range 2-8 kHz showed a significant difference with the brown-eyed subjects developing least TTS, and the blue-eyed subjects most TTS.

Adolescent↗
PubMed1991

A multivariate representation and analysis of DNA sequence data.

A new way to represent and analyze DNA sequence data is described. This approach complements methods currently used, in that it allows the systematic part of the variation between different sequences to be modeled. This can prove as informative as absence of variation (homology), which is the most widely used criterion for comparing sequence data. A multivariate sequence-activity model (SAM), for DNA-promoter sequences is presented, by which the relative promoter strength is modeled in terms of the primary DNA-sequence. The model is shown to have a good predictive capability. The coefficients from the model are interpreted, and used to design new structures predicted to be strong promoters in the system investigated. The approach described is also applicable to other kinds of sequence data, e.g. RNAs, proteins or peptides.

Base Sequence↗
PubMed1990

Insulin sensitivity and glucose-induced insulin response changes during adolescence.

Recently we reported that insulin resistance and glucose induced insulin release are inversely correlated to age in young healthy siblings of diabetic patients. To confirm this pattern of change with age, the subjects were reexamined after two years. The study was limited to the age groups with the lowest insulin sensitivity, i.e. 14.0-15.9 years for females and 16.0-17.9 years for males. All five girls and four of five boys showed an increased insulin sensitivity as measured by the somatostatin-insulin-glucose infusion test (p = 0.02). All subjects showed a decrease in fasting levels of insulin-like growth factor 1 (IGF-1) (p less than 0.01) during the observation period. All except one showed an increase in the levels of dehydroepiandrosterone sulphate (DHEA-S) (p less than 0.01). These data confirm that insulin sensitivity increases in the late teenage period. The parallelism to the changes of IGF-1 indicate that the pubertal changes in insulin sensitivity may partly be caused by growth hormone. Our data contradict the hypothesis that the low insulin sensitivity of puberty is due to the increased levels of DHEA-S.

Adolescent↗
PubMed1990

A comparison of the variability in thresholds measured with insert and conventional supra-aural earphones.

The purpose of this study was to evaluate the reliability and comparability of the commercially available insert earphone Etymotic Research ER-3A and the commonly available supra-aural TDH earphone. Thirteen subjects were tested five times with the ER-3A and five times with TDH-49P with MX-41/AR cushions. Threshold determinations were obtained utilizing a sweep-frequency audiometer in the range 0.25-8 kHz. The results showed that the reliability of the ER-3A earphone as measured by intra-individual variation, was comparable to that obtained with the TDH earphone. No evidence was found indicating an increased variability due to the positioning of the insert earphone's coupling device in the ear canal. Comparison of thresholds obtained with both devices indicated that the manufacturer's suggested correction values were appropriate.

Adult↗
PubMed1990

The influence of inner ear melanin on susceptibility to TTS in humans.

In order to investigate the function of the inner ear melanin, the relationship between skin pigmentation and noise-induced temporary hearing loss (TTS) was studied. Forty-four normal-hearing Caucasian subjects were divided into three groups according to their sun sensitivity. Hearing thresholds before and after exposure were ascertained with a computerized sweep frequency audiometer in the frequency range 2-8 kHz. The noise exposure consisted of a 1/3-octave band-filtered noise with a centre frequency of 2 kHz at 105 dB SPL for 10 min. The mean TTS in the frequency range 2-8 kHz showed statistically significant differences between the three groups, i.e. the most pigmented subjects developed least TTS, and the least pigmented subjects most TTS.

Adolescent↗
PubMed1990

Peptide QSAR on substance P analogues, enkephalins and bradykinins containing L- and D-amino acids.

Peptide QSARs are constructed for substance P analogues, enkephalins (two examples) and bradykinins containing both L- and D-amino acids. As descriptors in the QSARs, the previously developed descriptors z1 (hydrophobicity), z2 (bulk) and z3 (electronic effect) are used together with a qualitative variable coding for variation in chirality. Two parametrizations of the peptide sequences are tested. In the first no chiral description is used at all, and in the second chirality is described by the qualitative variable. It is concluded that for the current series of peptides, the biological response to variation in amino acid sequence and chirality can be modelled.

Amino Acid Sequence↗
PubMed1989

Elevated proinsulin in healthy siblings of IDDM patients independent of HLA identity.

Based on the recent demonstration of elevated serum proinsulin levels in cystic fibrosis patients with impaired glucose tolerance, it was hypothesized that proinsulin could be an indicator of altered beta-cell function. We therefore analyzed fasting proinsulin levels in 99 siblings of insulin-dependent diabetes mellitus (IDDM) patients, most of them discordant for diabetes for greater than 6 yr. The results from this group were compared with the results from 41 healthy age- and sex-matched control subjects with no family history of diabetes. Median (range) fasting proinsulin in siblings was 8.9 pM (1.7-58 pM) vs. 3.8 pM (less than 1.2-28 pM) in control subjects (P less than .00001). There was no difference between the groups in fasting blood glucose concentrations. Both groups had fasting insulin concentrations within the normal range with a tendency toward lower values in the siblings: 108 pM (60-237 pM) vs. 118 pM (71-175 pM) (P = .07). The 99 siblings were subdivided into groups according to HLA sharing with their diabetic proband. The concentration of proinsulin, insulin, and blood glucose among the groups of 33 HLA-identical, 40 HLA-haploidentical, and 26 nonidentical siblings did not differ significantly. The fasting proinsulin level did not correlate with fasting levels of insulin, blood glucose, age, or body weight. We conclude that fasting proinsulin is elevated in healthy siblings of IDDM patients, whereas fasting insulin is normal or slightly decreased independent of HLA identity with their diabetic sibling. Elevated proinsulin levels could represent a family trait, perhaps mirroring a beta-cell more vulnerable to destruction, or it could reflect previous beta-cell damage that does not lead to IDDM.

Adolescent↗
PubMed1989

The influence of carbogen on susceptibility to TTS.

A group of 20 male subjects were exposed to noise in each of four separate conditions. In two conditions they inhaled carbogen (95% oxygen, 5% carbon-dioxide). In two others they inhaled compressed air. In two conditions they were exposed to noise after inhalation and in two they were exposed to noise during the inhalation. The results indicated that carbogen inhalation reduced the magnitude of TTS but only in the 'During' condition.

Adolescent↗
PubMed1988

The influence of physical exercise on susceptibility to noise-induced temporary threshold shift.

In order to investigate whether physical exercise would influence susceptibility to temporary threshold shift (TTS), 9 subjects were exposed to a narrow-band noise at 105 dB SPL for 10 min three times in each of four test conditions. In three of the test conditions, noise exposure was combined with physical exercise at a level of 40% of the individual subject's maximum work capacity. Under these conditions, subjects were exposed to the noise before, during, or after exercise. In the fourth condition, subjects were exposed to the noise only. The results indicated that noise with simultaneous exercise increased the TTS susceptibility when compared with the other test conditions (p less than or equal to 0.05).

Adult↗
PubMed1988

Development of insulin antibodies, metabolic control and B-cell function in newly diagnosed insulin dependent diabetic children treated with monocomponent human insulin or monocomponent porcine insulin.

One hundred and thirty eight patients participated in a two-year randomized, double-blind multicentre trial to compare monocomponent human insulin and porcine insulin in the treatment of newly diagnosed insulin dependent diabetic children with respect to development of insulin antibodies, metabolic control and B-cell function. There was no difference between the two patient groups throughout treatment either in the level of IgG insulin binding or the percentage of patients with insulin antibodies (IgG-insulin greater than 0.012 U/l). However, the estimated mean of log insulin binding values in the antibody positive patients alone was significantly lower (p less than 0.05) in the human insulin treated group at all times apart from 1 and 18 months (e.g., human insulin group at one and two years: 0.104 and 0.152 U/l, porcine insulin group at one and two years: 0.162 and 0.212 U/l). The insulin antibodies in both patient groups bound equivalent amounts of human and porcine insulin tracer. Metabolic control, insulin dosage and B-cell function in the two treatment groups were similar throughout the treatment period. It is concluded that in newly diagnosed insulin dependent diabetic children monocomponent human insulin is slightly less immunogenic than monocomponent porcine insulin, and equally effective in overall metabolic control.

Animals↗
PubMed1987

Glucose-induced insulin response and insulin sensitivity is not related to HLA-type but to age in young siblings of type 1 (insulin-dependent) diabetic patients.

Glucose-induced insulin response and insulin sensitivity were studied in 32 HLA-identical, 38 haplo-identical and 24 non-identical, islet-cell-antibody-negative, healthy siblings of young Type 1 (insulin-dependent) diabetic patients (age range 10-28 years). No significant differences were obtained between HLA-identical, HLA-haplo-identical siblings and HLA-non-identical siblings in insulin response using an i.v. glucose infusion test even when the insulin sensitivity as estimated by the somatostatin-insulin-glucose infusion test was taken into account. A significant inverse correlation to age was found for both insulin response (r = -0.24, p = 0.02) and insulin sensitivity (r = -0.36, p less than 0.01) in the young siblings studied.

Adolescent↗
PubMed1987

C2 deficiency, moderately low IgG2 concentrations and lack of the G2m(23) allotype marker in a child with repeated bacterial infections.

C2 deficiency was demonstrated in an 11-year-old boy with a past history of recurrent purulent otitis media, pneumonia, H. influenzae meningitis and S. pneumoniae septicaemia. The major histocompatibility complex haplotypes present, A10, B18, DR2, BF*S, C2*QO, C4*A4, C4*B2 and A28, B18, DR2, BF*S, C2*Q0, C4*A4, C4*B2, were in accord with previous observations in C2 deficiency. The concentrations of C1q, C5, factor B and factor D were in the low normal range and the hemolytic activity of the alternative pathway was slightly decreased. In addition, the patient showed moderately low IgG2 concentrations and lacked the IgG2 subclass marker G2m(23). The findings indicate that the patient's susceptibility to bacterial infections may be due to C2 deficiency in combination with the presence of an IgG allotype associated with impaired antibody responses to carbohydrate antigens.

Bacterial Infections↗