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Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 559 records · Page 31Linked to original sources

Comparison of phototherapy (UV-B) and photochemotherapy (PUVA) for clearing and maintenance therapy of psoriasis.

One hundred eighty-three patients with psoriasis were treated with UV-B irradiation or oral methoxsalen plus longwave UV light (PUVA). Patients treated with PUVA, in the initial and maintenance period, achieved in general a higher therapeutic score (95% to 100% clearance) than those receiving UV-B therapy. However, taking 80% to 100% improvement as criterion, no difference was found between initial UV-B and PUVA therapy, if less than 50% of the skin surface was affected by psoriasis. If more than 50% of the skin was involved, PUVA was better than UV-B therapy. The maintenance treatment frequency for the UV-B-treated patients for more than a year seemed to be higher than for PUVA-treated patients. A positive correlation was found between response to sunbathing (questionnaire survey) and the response to UV-B phototherapy. An extra UV-B treatment to the leg lesions appeared useless.

Actuarial Analysis↗

Dependence of the shape of the plasma fibronectin molecule on solvent composition. Ionic strength and glycerol content.

Fibronectin has been purified to apparent homogeneity according to measurements of molecular weight and diffusion constant from light scattering and sedimentation in the analytical ultracentrifuge. This gives two estimates of molecular weight close to 500,000. (The difference with the gel electrophoretic value of 440,000 may indicate the presence of some material of molecular weight higher than that of the monomer.) The (corrected) diffusion constant is found to decrease with ionic strength, much more rapidly in 30% glycerol than in water. A corresponding change occurs when the glycerol content is varied from 0 to 30% at moderate ionic strength, but at very low ionic strength the diffusion constant does not depend on glycerol content. It is concluded that fibronectin can occur in two extreme conformations: the open form, in 30% glycerol at moderate ionic strength, should correspond to the extended shapes visualized by others by electron microscopy of samples prepared from solutions containing glycerol, while the closed form occurs under more physiological conditions. The Stokes radii of these forms, 14.5 and 9.6 nm, respectively, have been compared with calculated Stokes radii of chains of beads of overall length 140 nm having varying stiffness, simulated by a Monte Carlo procedure. These have a Stokes radius of 14.5 nm when made relatively extended to where the distance between chain ends averages 90 nm, as observed in the electron micrographs. When these chains are made very flexible, the Stokes radius reaches a limit of about 10 nm, apparently a lower limit to which a randomly coiled molecule of this size and volume may collapse in a disordered fashion. These results and electron micrographs obtained at low ionic strength suggest a tangled model of the compact form, rather than the ordered model recently proposed by others. Finally, some speculation is offered in regard to a possible physiological role of a conformation change of fibronectin.

Fibronectins↗

A collaborative calibration study of reference materials for thromboplastins.

In a collaborative study of ten laboratories performed mainly within the framework of the BCR (the European Community Bureau of Reference), five thromboplastins were calibrated against the WHO (World Health Organisation) primary international reference preparation 67/40. Of these five thromboplastins, three were BCR reference materials (BCT/099, OBT/79 and RBT/79) and two were WHO secondary international reference preparations (68/434 and 70/178). Human brain tissue type is represented by 67/40 and BCT/099; bovine type by 68/434 and OBT/79, and rabbit type by 70/178 and RBT/79. The calibration relations are expressed in terms of a linear relationship between the logarithms of the prothrombin times, measured in seconds.

Calibration↗

Evidence for the localization of a calcium-binding site in the amino-terminal disulphide knot of fibrin (ogen).

Human fibrinogen has three calcium-binding sites. Two of these are related to the carboxyl-terminal 13K ends of the gamma-chains. In order to investigate the possible localization of the third binding site in the central domain of fibrinogen, the amino-terminal disulphide knots (NDSK) of human fibrinogen and fibrin were prepared by cyanogen bromide degradation. Their calcium-binding properties were investigated by equilibrium dialysis. The NDSK's of fibrinogen and fibrin appeared to have 0.8 binding sites (Kd = 1.8 X 10(-4) M) and 0.9 binding sites (Kd = 3 X 10(-4) M), respectively. We conclude that the third calcium-binding site of fibrin(ogen) is located in the central symmetrical domain of the molecule (NDSK).

Binding Sites↗

Fibrin assembly.

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Calcium↗

Discriminant analysis of the localization of aggression-inducing electrode placements in the hypothalamus of male rats.

Over 400 sites in the hypothalami of 270 male CPB/WE-zob rats were electrically stimulated in order to induce fights between males. The localization of electrodes inducing fights seems to differ from the localization of electrodes in which no fights can be induced. The differences in localization were detected and tested by a non-parametric discriminant analysis. The results were plotted by computer in a stereotaxic atlas of the hypothalamus of the CPB/WE strain. The method delimits areas within the hypothalamus where the probability to induce aggression is high, intermediate or low. Moreover, the procedure allows discrimination between areas where the thresholds for attack behaviour are generally lower than elsewhere and where the fiercest forms of attack are induced. None of the areas delimited coincide with a classical subdivision of the hypothalamus. Parts of the perifornical, anterior, lateral and ventromedial hypothalamus seem to be involved. The methods developed here may help to relate stimulation-induced aggression to other characteristics of the 'aggressive' area which cannot be obtained directly from fighting rats such as cytological, endocrinological, biochemical or physiological data. In addition, the procedure may help to settle disputes on the specificity of the localization of neural substrates of other stimulation-induced behaviours. The methods to discriminate between overlapping 3-dimensional reconstructions validated here for aggressive responses, can also be applied to other types of stereotaxic data and other types of effects, such as electrical, hormonal or other physiological responses. They may be especially useful if the localization of the neural population involved is not yet known, and unknown current-spread or diffusion of substances complicates the interpretation of stereotaxic data.

Aggression↗

Purification and partial characterization of a D-like fragment from human fibrinogen, produced by human leukocyte elastase.

Digestion of human fibrinogen with human leukocyte elastase in the presence of Ca2+ yields a D-like fragment of Mr 93000. This fragment was purified by gel filtration on Sephacryl S-200 followed by chromatofocusing. The purified fragment was partially characterized and compared with a fragment termed D-cate, which is produced by plasmin digestion of fibrinogen in the presence of Ca2+. The molecular weights of the constituent chains of the D-like fragment and D-cate were similar. The D-like fragment precipitated with antisera directed against D-cate, but not with antisera against fragment E. The name D-elastase for the fragment is suggested. Differences between the D-elastase and D-cate fragments were found in amino-terminal amino acids, in isoelectric point and in the expression of D antigenic determinants. Two major functional differences were demonstrated: fragment D-elastase had a much stronger anticlotting potency than D-cate and the binding of Ca2+ by D-elastase and D-cate differed qualitatively and quantitatively. Since it has been suggested that the calcium-binding and anticlotting properties of D-cate are related to a carboxyl-terminal 13000 stretch of the gamma-chain, the present findings for D-elastase indicate that the differences in these properties between D-cate and D-elastase are due to differences in this area of the molecule.

Calcium↗

A comparison between the diagnostic efficacy of 99mTc-MDP, 99mTc-DPD and 99mTc-HDP for the detection of bone metastases.

We have investigated the clinical efficacy for the detection of bone metastases of two recently marketed bone-seeking radiopharmaceuticals, HDP and DPD, compared with traditionally used MDP. Twenty patients received 15 mCi 99mTc-MDP; after assessment ten of these patients later received 15 mCi 99mTc-DPD and ten other patients of this group were injected with 15 mCi 99mTc-HDP. Scintigraphy took place 3 h after tracer injection. Quantitative analysis included the calculation of normal bone to soft tissue ratios, lesion to soft tissue ratios and lesion to normal bone ratios for all three radiopharmaceuticals. Visual inspection of the scintiphotos revealed the same number of bone lesions at the same localisations. Statistical evaluation of our quantitative data showed that the lesion to normal bone ratio was significantly higher for MDP than for DPD. No further significant differences in the uptake in normal bone or in the metastatic lesions were found between all three radiopharmaceuticals. It is concluded that the new bone-seeking agents DPD and HDP do not possess clinical advantages over MDP for the detection of skeletal metastases.

Adult↗

The Hemalog D automated differential counter in the diagnosis of hairy cell leukemia.

We studied the peripheral blood of 37 patients with hairy cell leukemia (HCL) prior to (n = 24) or following (n = 19) splenectomy, in the Hemalog D multi-channel white cell differential counter, to investigate whether the apparatus could contribute to the (early) diagnosis of this entity and to the differential diagnosis of HCL from atypical hairy cell leukemia (AHCL; n = 9), chronic lymphocytic leukemia (CLL; n = 21) and leukemic non-Hodgkin lymphoma of low-grade malignancy (LNHL; n = 19). HCL showed almost invariably monocytopenia, neutropenia and an increased percentage of LUC, with a rather typical picture of the X-Y display of the peroxidase channel. The percentage of hairy cells closely correlated with the percentage of the LUC from the Hemalog D. Discriminant analysis using several parameters of the Hemalog D differential count resulted in a complete separation of HCL from CLL, and a fair, although not complete, distinction of HCL from AHCL and LNHL. It was impossible to discriminate between AHCL and LNHL. The most important discriminating (single or combined) parameters were the absolute monocyte count, the TWBC and the absolute neutrophil number. It is concluded that the Hemalog D is a valuable tool in the (early) diagnosis of HCL and in the discrimination between HCL and other leukemic lymphoproliferative disorders.

Humans↗

Radiation-induced head and neck tumours: is the skin as sensitive as the thyroid gland?

Six hundred and five persons, randomly selected from a cohort of 2400 patients who had been irradiated 16-46 yr previously for benign diseases in the head and neck region, were traced, recalled and examined for radiation-associated tumours. Three hundred and sixty-seven patients were alive, 179 had died and 66 had emigrated. Two hundred and fifty-seven patients were clinically examined, 87 refused or were not able to participate and 16 could not be contacted. Eighteen of the clinically examined patients had been or were being treated for 20 skin carcinomas with a mean latency of 37 yr. In this group only 7 carcinomas of the thyroid gland were observed, with a mean latency of 38 yr. Eleven carcinomas of the skin and 3 of the thyroid gland were reported in the group which was examined by means of questionnaires. The observed number of carcinomas of the skin is higher than expected according to the dose-effect relationship of UNSCEAR, whereas the number of carcinomas of the thyroid gland is lower. It is concluded that there might be less difference in susceptibility for the induction of tumours by ionizing radiation between the skin and the thyroid gland than is commonly assumed.

Dose-Response Relationship, Radiation↗

Kinetics of five benzodiazepine hypnotics in healthy subjects.

Kinetics of five benzodiazepine hypnotics (15 mg flurazepam, 1 mg flunitrazepam, 5 mg nitrazepam, 10 mg temazepam, and 0.5 mg triazolam) were compared in the same group of 12 healthy subjects. Plasma concentrations of parent drugs were determined by capillary gas chromatography with electron-capture detection. For flurazepam, the N-desalkyl metabolite (DAF) was measured. Flunitrazepam, nitrazepam, temazepam, and triazolam were rapidly absorbed, although there was considerable variability; mean peak times (ranges) were: 1.3 (0.3 to 3) hr, 1.8 (0.7 to 6) hr, 1.2 (0.3 to 4) hr, and 1.1 (0.7 to 2) hr. Plasma concentrations of DAF increased rather slowly and reached their maximum between 3 and 48 hr after flurazepam. There were considerable differences in elimination t1/2s, with means of 35 (15 to 66) hr for flunitrazepam, 28 (22 to 33) hr for nitrazepam, 12 (8 to 22) hr for temazepam, 2.4 (1.4 to 3.9) hr for triazolam, and 84 (40 to 114) hr for DAF. Sex differences in elimination t1/2 were only observed for DAF: 99 hr in women and 69 hr in men. Our results show that there are considerable differences in the kinetics of the diazepines.

Adult↗

Computer simulation of the dynamics of hydrated protein crystals and its comparison with x-ray data.

The structure and dynamics of the full unit cell of a protein (bovine pancreatic trypsin inhibitor) containing 4 protein molecules and 560 water molecules have been simulated by using the molecular dynamics method. The obtained structure, atom positional fluctuations, and structure factors are compared with x-ray values. A way of calculating the motional contributions to structure factors is proposed.

Animals↗

Effect of warm ischemia time and HLA (A and B) matching on renal cadaveric graft survival and rejection episodes.

In a retrospective single-center study the influence of warm ischemia time and simultaneous influence of HLA (A and B) matching on one-year renal graft survival was analyzed in 170 adult recipients of primary cadaveric renal grafts. One-year survival of grafts with warm ischemia times longer than 50 min was only 40% (n = 10). When warm ischemia time was shorter than 50 min, a 1-min increase of warm ischemia time correlated with 1% decrease in one-year graft survival as a result of rejection. This detrimental effect of warm ischemia time on graft survival was not yet significant one month after transplantation, but became more evident as follow-up time was lengthened. Warm ischemia time also correlated with the number of reversible rejection episodes in patients with a graft functioning for longer than one year (P less than 0.04). The beneficial influence of HLA (A and B) matching on one-year graft survival was significant (P less than 0.05 log linear test). This influence was even more evident with longer warm ischemia times. It is concluded that warm ischemia has a detrimental influence on graft survival that is mediated by rejection, and it is suggested that this might be due in part to altered presentation or expression of HLA-antigens of ischemically damaged kidney tissues.

Adult↗

Diagnostic criteria in Sézary's syndrome: a multiparameter study of peripheral blood lymphocytes in 32 patients with erythroderma.

In order to define additional diagnostic criteria for the early diagnosis of Sézary's syndrome (SS), peripheral blood lymphocytes of 32 patients with erythroderma, including 8 patients with SS, 4 patients with erythrodermic mycosis fungoides, 14 patients with an erythroderma on the basis of atopic or chronic dermatitis, and 6 patients with erythrodermic psoriasis, were investigated by computer-assisted morphometry. The degree of nuclear indentation, expressed as the nuclear contour index (NCI), was measured on electron micrographs. The mean NCI and the percentages of cerebriform mononuclear cells (CMC), defined by a NCI greater than or equal to 6.5, were calculated. In addition, the percentages of lymphocytes, T and B cells, and the distribution of T-cell sub-populations as defined by Fc-receptors (T mu, T gamma) and monoclonal antibodies (OKT3, OKT4, OKT8, HLA-DR) were determined. Statistical analysis showed as most discriminating parameters for the differentiation between SS and benign forms of erythroderma: high percentages of lymphocytes (50% or more), an expanded OKT3+, OKT4+ population with an OKT4/OKT8 ratio greater than 10, a mean NCI value greater than or equal to 5.5, the presence of more than 20% CMC, as well as the presence of cells with a NCI greater than or equal to 11.5. The total leukocyte and lymphocyte counts, as well as the percentages of B, T, T mu, and T gamma cells had limited value for the early diagnosis of SS.

Aged↗

Pharmacokinetics of brotizolam in healthy subjects following intravenous and oral administration.

Pharmacokinetics and bioavailability of brotizolam after i.v. and oral administration were studied in healthy young volunteers. Kinetic parameters after i.v. administration were: volume of distribution 0.66 +/- 0.19 1/kg, total plasma clearance 113 +/- 28 ml/min, distribution half-life 11 +/- 6 min, and elimination half-life 4.8 +/- 1.4 h (mean values +/- s.d.). Kinetic parameters after oral administration were: absorption lag-time 8 +/- 12 min, absorption half-life 10 +/- 11 min, and elimination half-life 5.1 +/- 1.2 h (mean values +/- s.d.). Bioavailability of brotizolam was 70 +/- 22% when calculated by comparing oral and intravenous area-under-curve values, corrected for intra-individual half-life differences. An alternative calculation method, which is relatively independent of large clearance variations, provided a bioavailability of 70 +/- 24% (range: 47-117%).

Administration, Oral↗