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Biomedical subjects

J Hermans

Publications and source records attributed to J Hermans.

At least 541 records · Page 30Linked to original sources

Subunit interactions in human plasma fibronectin.

The fibronectin molecule was split chemically into its two constituent chains (mol. wt. 220,000) by mild reduction with dithiothreitol. However, physical properties (molecular weight and diffusion coefficient from light scattering, and elution in gel exclusion chromatography) remained those of intact fibronectin, except (reversibly) in the presence of denaturants which also change the conformation of non-reduced fibronectin to a more open form. Similarly, during digestion of fibronectin by plasmin to fragments of molecular weight less than 200,000, the light scattering intensity drops to roughly half in 30% glycerol but not in the absence of glycerol. These results suggest that the compact conformation of native fibronectin is stabilized by specific noncovalent contacts between constituent chains.

Dithiothreitol↗

Characterization of soluble polymerized fibrin formed in the presence of excess fibrinogen fragment D.

Polymerization of fibrin is inhibited in the presence of excess fibrinogen fragment D. This study was performed in order to test the proposal that these inhibited solutions contain short linear polymers of fibrin (protofibrils) whose further polymerization is prevented as a result of attachment of a molecule of fragment D at each end. Negative-stain electron micrographs, intrinsic viscosities, angular dependence of light scattering intensity, and kinetics of the increase of the scattered intensity with polymerization all were found to support the above model of the inhibited polymer and to reflect the presence of a broad distribution of the lengths of the inhibited fibrin polymers. Furthermore, sodium dodecyl sulfate-polyacrylamide gel electrophoresis of polymers stabilized with gamma-dimer cross-links introduced by factor XIIIa demonstrates cross-linking of fragment D to fibrin oligomers. Cross-linked polymers have been separated from excess fragment D by gel exclusion chromatography in 1 M urea. (In the absence of urea, the purified polymers very slowly associate to fibers.) The observation of the relative stability of short isolated inhibited protofibrils and the decrease or absence of inhibition of fibrin gelation when fragment D was added to solutions in which fibrin had been given time to polymerize to long protofibrils demonstrate that the inhibitory effect of fragment D occurs as a result of inhibition of the first fibrin polymerization step.

Animals↗

Anticoagulant properties of purified X-like fragments of human fibrinogen produced by degradation with leukocyte elastase.

The anticoagulant properties of fibrinogen digestion products change with stage of digestion. On digestion with leukocyte elastase, in the presence of calcium ions, the anticoagulant potency of fibrinogen digests first increases, then decreases sharply, and in late stages increases again. This is different from plasmin digestion where only an increase in anticoagulant activity is seen followed by a slow decrease. From SDS-gel electrophoresis it appears that both the early rise and the decrease in anticoagulant activity are associated with the stage of elastase-produced X-like fragments. This is confirmed with pure fragments: X-like fragments (purified from elastase digests of fibrinogen of different stages by ammonium sulphate precipitation and ion-exchange chromatography) give an increase and decrease in anticlotting activity which correlates very well with that of the potency of the digest from which they are purified. As expected, and in contrast with (late) plasmic X-fragments, late elastase X-like fragments have a low anticoagulant potency. The molecular basis for the gain and loss in anticoagulant activity going from early to late X-like fragments is obscure. Immunological tests, calcium-binding experiments and affinity chromatography on immobilized thrombin-activated NDSK suggest that the changes in anticoagulant activity are not due to a proteolytic change in the carboxyl-terminal part of the gamma-chain in the D moiety of the molecule. Our data suggest a correlation with the stage of digestion of the A alpha-chain in the X-like fragments.

Anticoagulants↗

Psoriasis and arthritis. I. A population study.

In a population survey of 3659 persons aged 20 years or older, no association was found between psoriasis and rheumatoid arthritis. Inflammatory, degenerative and soft tissue rheumatic diseases occurred in 59% of the psoriatics and 46% of the controls. However, the mean number of rheumatological diagnoses in the psoriatics was 1.1 and in the controls 1.3. Features of psoriasis were found in 41 individuals (1.1%). Features of inflammatory arthritis (RA + past-polyarthritis) were established in 5% and 2.2% of the psoriatics and the controls respectively, but this difference is not significant. Because patients with psoriasis have complaints associated with the locomotor system more frequently than non-psoriatic people, it seems likely that the referral rate of the former to special clinics is higher.

Adult↗

Psoriasis and arthritis. II. A cross-sectional comparative study of patients with "psoriatic arthritis" and seronegative and seropositive polyarthritis: clinical aspects.

Arthritis of the terminal joints of the hands and feet occurred more frequently (P less than 0.015) in patients with seronegative poly-arthritis combined with psoriasis (S- P+; n = 92) than in patients with seronegative polyarthritis alone (S- P-; n = 72). However, the prevalence of affection of these joints was too low to consider this feature a sensitive marker for psoriatic arthritis. Furthermore, neither asymmetrical joint involvement nor the absence of ulnar deviation of the fingers appeared to be characteristic of this disease. A positive correlation was found between the presence of nail psoriasis and limitation of function of the distal interphalangeal (DIP) joints. The DIP finger joints and the interphalangeal joints of the toes were affected more often in the S- P+ group than in patients with seropositive polyarthritis without psoriasis (S+ P-; n = 46), but arthritis of the other joints was observed more frequently in the latter group.

Adult↗

Psoriasis and arthritis. III. A cross-sectional comparative study of patients with "psoriatic arthritis" and seronegative and seropositive polyarthritis: radiological and HLA aspects.

In a group of patients with seronegative polyarthritis and psoriasis, the radiological features and the incidence of histocompatibility antigens were compared with those of a group of patients with seronegative polyarthritis but not psoriasis. No radiological criteria proved to be characteristic of psoriatic arthritis. In the group of patients with seronegative polyarthritis and psoriasis, erosions of the distal interphalangeal (DIP) joints were seen more frequently and were more severe than in the group of patients with seronegative arthritis without psoriasis. For the group of patients with seronegative polyarthritis and psoriasis, correlation was found between psoriatic nail lesions and erosions of the DIP joints, but this correlation was not found between the nail involvement and erosion of the adjacent DIP joint. No significant differences were found for the incidence of histocompatibility antigens between patients with seronegative polyarthritis with or without psoriasis. However, differences were found between these two groups and either the seropositive polyarthritis group or blood bank donors.

Adult↗

Combined modality treatment of short duration in small cell lung cancer.

Fifty-seven patients with small cell lung cancer (SCLC) (limited disease = LD in 23, extensive disease = ED in 34) received the combination of CCNU, cyclophosphamide, vincristine and methotrexate (CCOM). A mean number of only 6 (range 1-17) courses of chemotherapy were given. All LD patients received consolidation locoregional radiation (30 Gy) after two courses of chemotherapy. A complete response (CR) was obtained in 61% of LD and 12% of ED patients, and a partial response in 22 and 35% respectively. Median survival was 54 and 34 weeks for LD and ED respectively. Five LD patients survived more than 2 yr, three of them remaining disease-free 4 yr after the cessation of treatment. A subset of 12 LD patients achieving a CR after two courses of chemotherapy was randomized to receive maintenance chemotherapy or observation only after the consolidation radiotherapy. In this small-sized randomized trial maintenance treatment showed a significant decrease of the patients' quality of survival compared to no maintenance treatment. We conclude that combined modality treatment of short duration proved effective in SCLC. Future randomized studies are necessary to show whether prolonged chemotherapy has a meaningful impact on survival, or otherwise the resulting morbidity will plead against it.

Adult↗

Quantification of the effect of anti-anaerobic drugs in experimental Bacteroides fragilis infection in mice.

As a basis for the quantitation of the effect of anti-anaerobic drugs in vivo, an experimental thigh infection in mice was developed in which co-inoculation of Bacteroides fragilis and Escherichia coli is obligatory for proliferation of Bact. fragilis. The inhibitory effect of metronidazole and tinidazole on the proliferation of Bact. fragilis was assessed in this model. Both metronidazole and tinidazole showed a significant dose-effect relationship with respect to the outgrowth of Bact. fragilis but not that of E. coli. The effect of both drugs on Bact. fragilis was similar and at all dosage levels a significant correlation was found between the numbers of Bact. fragilis and E. coli.

Animals↗

Comparative clinical study on the absorption of orally administered amoxycillin and bacampicillin.

In nine consecutive hospitalized patients treated with either ampicillin or amoxycillin, studies on the pharmacokinetics of orally administered amoxycillin and bacampicillin gave a mean absorption of 73% (+/- 15%) of the dose for amoxycillin and 65% (+/- 17%) for bacampicillin. An analysis of variance showed that the difference between the two drugs has only borderline significance (P less than 0.10). These mean values are lower than those reported in the literature for healthy volunteers, and the variation between patients is also larger. The mean absorption rates found for the two drugs did not differ from those found in healthy volunteers, amoxycillin being absorbed significantly more slowly than bacampicillin (P less than 0.02), but there were also large differences between patients.

Administration, Oral↗

Bone marrow transplantation for acute nonlymphoblastic leukaemia: a survey of the European Group for Bone Marrow Transplantation (E.G.B.M.T.).

Between 1979 and 1982, 229 patients with acute nonlymphoblastic leukaemia in remission were given allogeneic bone marrow transplants from HLA-identical siblings. Data on 183 patients transplanted in first complete remission were compared with results of 46 patients transplanted in second or subsequent remission. The 2-year actuarial survival rate was 53% for patients transplanted in first remission and 36% for patients transplanted in second or subsequent remission (P = 0.02). The probability of survival was related to the age of the patient (P = 0.02) and of the donor (P = 0.0002). The 2-year actuarial leukaemia recurrence rate was 12% for patients transplanted in first remission and 44% for patients in a subsequent remission (P = 0.10). Other factors correlating with a higher probability of relapse after transplantation were the leukaemia subtypes M4 and M5 (P = 0.007), cyclosporin A used as prophylaxis of graft-versus-host disease (P = 0.008), and the absence of chronic (but not of acute) graft-versus-host disease (P = 0.003). These data indicate that prolonged survival can be achieved in approximately 50% of patients with acute nonlymphoblastic leukaemia who receive bone marrow transplants during their first complete remission. But modifications of pre- and post-transplant treatment should be considered to reduce the rate of relapse.

Acute Disease↗

Bone marrow transplantation for acute lymphoblastic leukaemia: a survey of the European Group for Bone Marrow Transplantation (E.G.B.M.T.).

Between 1979 and 1982, 192 patients with acute lymphoblastic leukaemia were given allogenic bone marrow transplants from HLA-identical siblings. Data on 57 patients transplanted in first remission were compared with the results in 96 patients transplanted in second remission, and 39 in third or subsequent remission. The majority of these patients were of the non-B non-T-ALL and T-ALL subtypes. The 2-year actuarial survival for non-B non-T-ALL was 58% for patients transplanted in first remission, 34% for second remission patients and 33% for patients transplanted in third or subsequent remission (P = 0.60). For patients with T-ALL, the survivals at 2 years for first and second remission transplant patients were 61% and 10%, respectively (P = 0.04). Multifactorial analysis demonstrated a significantly higher probability of survival for patients grafted in first remission (compared with more advanced remission states) and with bone marrow from young (age less than or equal to 20 years) donors. The 2-year actuarial risk of relapse for patients with non-B non-T-ALL transplanted in first remission was 0%, 32% and 69% for second and third or subsequent remission patients, respectively (P = 0.04). For T-ALL the actuarial risk of relapse at 2 years is 10% for first remission grafts and 48% for second remission grafts (P = 0.07). Only patients (with both non-B non-T/and T-ALL) transplanted in first remission have a high and stable probability of remaining in remission.

Actuarial Analysis↗

Role of HLA class II products in proliferative T-lymphocyte responses to PPD. Evidence of a regulatory influence associated with MB1.

HLA class II determinants were analysed for their role in monocyte-T-cell interactions in the proliferative response to purified protein derivative (PPD). Allogeneic cell combinations of monocytes and T cells were tested with a range of suboptimal PPD concentrations. For each cell combination tested, a summary measure to characterize the antigen-induced response curve was calculated by means of regression analysis of the response to the dose of PPD added, thus obviating a further need to correct for mixed lymphocyte reactivity. In 200 distinct monocyte-T-cell combinations, HLA-DR appeared to be the major restricting element. Additionally, a marginal influence of HLA-MB or -MT matching was observed and no evidence of HLA-SB-restricted responses. Remarkably, the HLA-MB1 specificity was significantly associated with low responsiveness in DR sharing monocyte-T-cell combinations, indicating a modulating role of MB1 in DR-restricted T-cell responses.

Epitopes↗

Polypoid lesions of the sigmoid colon: a comparison of single-contrast, double-contrast, and biphasic examinations.

The single-contrast (SC), double-contrast (DC), and biphasic examinations of the sigmoid colon in 51 patients with histologically proved sigmoid polyps 1.0 cm or greater in diameter were reviewed. In each case the polyps were radiographically detected and visualized by endoscopy. The radiographs of 49 patients without sigmoid polyps were similarly reviewed. The biphasic approach was significantly superior to the single-contrast examination in the detection of sigmoid polyps (p less than 0.05). The differences between SC and DC examinations as well as between DC and biphasic examinations were not significant. In the presence of diverticulosis, however, the biphasic approach proved to be significantly more sensitive than the DC examination. The greater sensitivity of the biphasic examination compared with SC was of borderline significance. It is concluded that in the presence of diverticulosis a combination of single- and double-contrast techniques can improve the sensitivity of the examination significantly in the detection of polypoid lesions.

Adenoma↗

Untreated Paget disease of bone studied by scintigraphy.

We determined that the concentration of radioactivity in a lesion of Paget disease correlates with the grade of radiological deformation and the frequency of pain; the total skeletal uptake correlates with the severity of the biochemical abnormalities. We suggest that the major determinant of uptake in untreated lesions is abnormal metabolic activity, and in lesions in remission it is structural deformation of mineralized tissue. It is likely that the metabolic activity, and possibly also the rate of progression of the individual lesions, will differ in the individual patient, and that metabolic activity determines the amount of deformation and the chance of pain. Lesions not visible on the radiograph usually show only low uptake of Tc-99m-Sn-EHDP; the majority of these lesions are asymptomatic and reflect low activity of the disease. Radiological differentiation between sclerotic and osteolytic lesions does not reflect differences in either scintigraphic uptake, metabolic activity, or pain.

Adult↗

Prognostic significance of immunologic phenotype in hairy cell leukemia.

Hairy cell leukemia (HCL) is a usually chronic B cell lymphoproliferative disorder. To evaluate the prognostic significance of the various heavy and light chain determinants of the surface immunoglobulins (slg), we analyzed the clinical data and immunologic phenotype of 64 patients with HCL. Sixty-two of the 64 patients showed slg, which was invariably of only one light chain type (kappa 33, lambda 29). The actuarial survival of the cases expressing kappa-light chains was significantly better than those with lambda-light chains (p less than 0.002). This difference persisted when only cases with gamma or alpha gamma heavy chains were considered. No differences between the kappa and lambda-subgroups were discovered with respect to parameters of clinical importance. The various heavy chain classes of slg did not correlate significantly with the survival time. These results suggest that the immunologic phenotype, in particular the light chain type, may be a prognostic factor in patients with HCL.

Adult↗