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Biomedical subjects

J Hendriks

Publications and source records attributed to J Hendriks.

At least 55 records · Page 3Linked to original sources

The active site of the bacterial nitric oxide reductase is a dinuclear iron center.

A novel, improved method for purification of nitric oxide reductase (NOR) from membranes of Paracoccus denitrificans has been developed. The purified enzyme is a cytochrome bc complex which, according to protein chemical and hydrodynamic data, contains two subunits in a 1:1 stoichiometry. The purified NorBC complex binds 0.87 g of dodecyl maltoside/g of protein and forms a dimer in solution. Similarly, it is dimeric in two-dimensional crystals. Images of these crystals have been processed at 8 A resolution in projection to the membrane. The NorB subunit is homologous to the main catalytic subunit of cytochrome oxidase and is predicted to contain the active bimetallic center in which two NO molecules are turned over to N2O. Metal analysis and heme composition implies that it binds two B-type hemes and a nonheme iron but no copper. NorC is a membrane-anchored cytochrome c. Fourier transform infrared spectroscopy shows that carbon monoxide dissociates from the reduced heme in light and associates with another metal center which is distinct from the copper site of heme/copper oxidases. Electron paramagnetic resonance spectroscopy reveals that NO binds to the reduced enzyme under turnover conditions giving rise to signals near g = 2 and g = 4. The former represents a typical nitrosyl-ferroheme signal whereas the latter is a fingerprint of a nonheme iron/NO adduct. We conclude that the active site of NOR is a dinuclear iron center.

Binding Sites↗

Graded retinoid responses in the developing hindbrain.

The purpose of this study was to make an explicit test of the idea that a retinoid could act as a morphogen, differentially activating genes and specifying anteroposterior (a-p) level in the developing vertebrate central nervous system (CNS). Our approach was to characterize the concentration-dependent effects of retinoic acid (RA) on the neural expression of a set of a-p patterning genes, both in vivo and in an in vitro system for neural patterning. Our results indicate that a retinoid is unlikely to specify a-p level along the entire CNS. Instead, our data support the idea that the developing hindbrain may be patterned by a retinoid gradient. Sequentially more posterior hindbrain patterning genes were induced effectively by sequentially higher RA concentration windows. The most posterior CNS level induced under our RA treatment conditions corresponded to the most posterior part of the hindbrain.

Animals↗

From NO to OO: nitric oxide and dioxygen in bacterial respiration.

Nitric oxide reductase (NOR) is a key enzyme in denitrification, reforming the N-N bond (making N2O from two NO molecules) in the nitrogen cycle. It is a cytochrome bc complex which has apparently only two subunits, NorB and NorC. It contains two low-spin cytochromes (c and b), and a high-spin cytochrome b which forms a binuclear center with a non-heme iron. NorC contains the c-type heme and NorB can be predicted to bind the other metal centers. NorB is homologous to the major subunit of the heme/copper cytochrome oxidases, and NOR thus belongs to the superfamily, although it has an Fe/Fe active site rather than an Fe/Cu binuclear center and a different catalytic activity. Current evidence suggests that NOR is not a proton pump, and that the protons consumed in NO reduction are not taken from the cytoplasmic side of the membrane. Therefore, the comparison between structural and functional properties of NOR and cytochrome c- and quinol-oxidizing enzymes which function as proton pumps may help us to understand the mechanism of the latter. This review is a brief summary of the current knowledge on molecular biology, structure, and bioenergetics of NOR as a member of the oxidase superfamily.

Bacteria↗

T-cell receptor variable region genes in cutaneous T-cell lymphomas.

The genes encoding the T-cell receptor (TCR) variable beta (TCRBV) regions were studied in skin biopsy samples from 24 patients with cutaneous T-cell lymphomas (CTCL), i.e. mycosis fungoides (n = 7), Sézary syndrome (n = 4), lymphomatoid papulosis (n = 3) and large cell CTCL with (n = 3) or without (n = 7) CD30 expression. A panel of 24 primers specific for TCRBV families 1-24 was designed and applied to cDNA using a semiquantitative reverse transcriptase coupled polymerase chain reaction (PCR) method. Three patients showed restricted expression of a limited number (1-3) of TCRBV families. In the remaining patients, an average of 17 (range: 13-22) different families was expressed. All patients showed elevated (> 10%) expression of individual families significantly higher than that seen in normal blood lymphocytes, but no preferential usage of particular gene families was observed. Direct sequence analysis of more than 60 PCR products revealed clonal TCR transcripts in 18 patients. A single T-cell clone, constituting 9-100% (mean: 26%) of the TCRBV mRNA, was present in 12 patients; two T-cell clones, constituting 13-72% (mean: 21.5%) of the TCRBV mRNA, were present in five patients; and three T-cell clones, accounting for < 0.5-13% of the TCRBV mRNA, were present in one patient. In the remaining six patients, clonal TCR transcripts could not be identified. It is concluded that most CTCL contain both clonal and non-clonal (reactive) T cells, and that the latter cells are more numerous than anticipated. These cells may be engaged in tumour immune reactions, although prospective studies and/or serial investigations are needed to elucidate this issue fully.

Adult↗

Exhaled nitric oxide (NO) is reduced shortly after bronchoconstriction to direct and indirect stimuli in asthma.

Exhaled NO is increased in patients with asthma and may reflect disease severity. We examined whether the level of exhaled NO is related to the degree of airway obstruction induced by direct and indirect stimuli in asthma. Therefore, we measured exhaled NO levels before and during recovery from histamine and hypertonic saline (HS) challenge (Protocol 1) or histamine, adenosine 5'-monophosphate (AMP), and isotonic saline (IS) challenge (Protocol 2) in 11 and in nine patients with mild to moderate asthma, respectively. The challenges were randomized with a 2-d interval. Exhaled NO and FEV1 were measured before and at 4, 10, 20, and 30 min after each challenge. NO was measured during a slow VC maneuver with a constant expiratory flow of (0.05 x FVC)/s against a resistance of 1 to 2 cm H2O. Baseline exhaled NO levels were not significantly different between study days in Protocol 1 (mean +/- SD: 4.8 +/- 1.8 ppb [histamine] versus 5.4 +/- 2.1 ppb [HS], p = 0.4) or in Protocol 2 (7.9 +/- 4.7 ppb [histamine], 8.3 +/- 5.2 ppb [AMP], and 7.2 +/- 3.7 ppb [IS], p = 0.7). A significant reduction in exhaled NO was observed directly after HS (mean +/- SEM: 39.2 +/- 3.9 %fall) and AMP challenge (32.3 +/- 7.3 %fall) (MANOVA, p < 0.001), respectively, whereas exhaled NO levels tended to decrease after histamine challenge. Isotonic saline challenge did not induce changes in exhaled NO (p = 0.7). There was a positive correlation between %fall in FEV1 and the %fall in exhaled NO after histamine, HS, and AMP challenge as indicated by the mean slope of the within-subject regression lines (p <= 0.04). We conclude that acute bronchoconstriction, as induced by direct and indirect stimuli, is associated with a reduction in exhaled NO levels in asthmatic subjects. This suggests that airway caliber should be taken into account when monitoring exhaled NO in asthma.

Adult↗

Chylothorax complicating left lower sleeve lobectomy.

Postoperative chylothorax is an infrequent but potential life-threatening complication and has most often been described following oesophageal resection. Its incidence after pulmonary resection is low, but has increased to 0.3-0.5%, probably due to more extensive types of resections and radical lymph node dissections. We report a case of chylothorax after a left sleeve lobectomy for a primary bronchogenic carcinoma, that was treated conservatively with chest tube drainage and a diet of medium chain triglycerides. Five additional case reports in English and French literature confirmed chylothorax after bronchoplastic procedures to be extremely rare. More frequent use of bronchial sleeve resection as alternative to pneumonectomy to save functional lung tissue, can increase the incidence of chylothorax after bronchoplastic procedures.

Aged↗

Mammographic screening after the age of 65 years: early outcomes in the Nijmegen programme.

We studied outcomes of mammographic screening in women older than 65 years. In 1975, breast cancer screening was started in Nijmegen, The Netherlands, for women aged 35-65 years. Since 1977, approximately 7700 older women have also been invited for biennial one-view mammography. This report is based on ten screening rounds from 1975 to 1994. The results of the subsequent screening rounds in the age groups 65-69 years, 70-74 years and 75 years and older were: participation rates 55%, 39% and 15%; screen-detected cancer rates 5.6%, 6.9% and 7.8%; interval cancer rates 2.0%, 1.8%, and 3.5%; and predictive values of referral 62%, 64% and 62% respectively. In all age groups, screen-detected patients had smaller tumours and a lower prevalence of axillary lymph node involvement than unscreened patients. Our conclusion is that, in women aged 65 years, and older, breast cancer can be detected at an earlier stage by mammographic screening.

Age Factors↗

Granulocyte-macrophage colony-stimulating factor (GM-CSF) counteracts the inhibiting effect of monocytes on natural killer (NK) cells.

GM-CSF is known to accelerate haematopoietic recovery following allogeneic bone marrow transplantation (BMT). In addition, it may restore and enhance both granulocyte and monocyte functions. Stimulation of monocyte functions may induce a direct or an indirect anti-leukaemic activity due to an increase of cellular cytotoxicity and production of cytokines which may result in a reduction of the relapse rate after BMT. NK cells may play a crucial role in this activity. Therefore we studied the influence of monocytes on NK activity in combination with GM-CSF. Lymphocytes and monocytes were isolated from buffy coats of healthy individuals by counterflow centrifugation elutriation (CCE). NK activity was exerted by CD3-CD56+ cell populations and could be enhanced by IL-2 incubation overnight. Incubation of CD3-CD56+ cells with GM-CSF in the presence or absence of IL-2 hardly influenced NK activity of the lymphocyte population. Low amounts of monocytes enhanced NK activity. NK activity in lymphocyte population in the presence of equivalent numbers of monocytes with or without IL-2 was strongly decreased irrespective of the effector:target ratio (ETR). This appeared not to result from sterical hindrance effects of the present number of cells. However, addition of GM-CSF abrogated the inhibition of NK activity by monocytes in the presence of IL-2. In monocyte fractions neither IL-2 nor GM-CSF yielded NK activity. Our findings indicate that GM-CSF can affect NK activity by counteracting the suppressing effects of monocytes, and hence may improve the outcome after BMT.

Cell Communication↗

Tonometry to assess the adequacy of splanchnic oxygenation in the critically ill patient.

Tonometry, a relatively non-invasive technique for indirectly measuring the intramucosal pH (pHi) of the gastrointestinal tract, has recently been developed for use in critically ill patients. Reports in the literature suggest that the technique is of greatest benefit to patients at risk of developing reductions in splanchnic oxygenation (decreased O2 delivery) in whom early detection of the ischemic episode could possibly guide treatment. Tonometry, although still at a relatively early stage in its clinical development, could be of value for selected patient groups although further evaluation of the technique is necessary.

Clinical Trials as Topic↗

[Favorable effects of rehabilitation in patients with CARA].

OBJECTIVE: To examine the effects of a rehabilitation programme in patients with asthma or COPD who have major complaints despite the fact that their pulmonary function is not severely disturbed. SETTING: Medical Centre Dekkerswald, Groesbeek. DESIGN: Prospective clinical trial. PATIENTS AND METHODS: The treated group consisted of 44 patients with an obstructive lung disease, FEV1 68.3% of predicted value. This group was compared with 43 patients in a control group. These were volunteers, who were comparable for pulmonary function, reversibility, age, sex, Quetelet index, pulmonary medication and educational level. These groups were examined for 2 years by means of tests and questionnaires. Changes from baseline values were analysed by covariance analysis. Patients followed a rehabilitation programme which consisted of an optimal medical treatment in combination with training of physical endurance, health education and psychological and social support. The duration of the programme was 3 months, 38 hours a week. RESULTS: Pulmonary rehabilitation had a long-term beneficial effect on endurance, several psychological valuables, consumption of medical care, attitude towards way of life, skills, coordination and smoking habits. Bronchial hyperresponsiveness, need of pulmonary drugs and complaints of cough and sputum production did not change after rehabilitation. Airway obstruction and subjective feelings of dyspnoea, allergy and hyperresponsiveness only decreased in the short term (less than I year). CONCLUSION: This study shows that pulmonary rehabilitation improves many variables in the short as well as in the long run. When COPD patients do not improve on conventional treatment, pulmonary rehabilitation should be considered.

Adaptation, Psychological↗

Incidence of retroviruses in some Brazilian groups.

The prevalence of human T lymphotropic virus type I (HTLV-I) and human immunodeficiency virus (HIV) antibodies was evaluated in Brazil among 116 aboriginal Indians living in a pre-Amazonian region, and in 44 patients with haematological malignant disorders being treated in Rio de Janeiro. Screening for the presence of antibodies to HIV was performed routinely for 17,224 blood donors at the National Cancer Institute, Rio de Janeiro, from January 1986 to May 1987. The results demonstrated that HIV infection was not endemic among Brazilian Indians, as none of them had antibodies to HIV, in contrast with the population of Rio de Janeiro, which showed a high prevalence (0.34%) of positivity among normal individuals. In a small group of patients with haematological disease only one with acute lymphoblastic leukaemia proved to be HIV-positive, the infection having been acquired through previous blood transfusion. None of the serum samples reacted with HTLV-I, including those of 17 non-Hodgkin's lymphoma patients. HTLV-I infection does not seem to be endemic in this country, but further large scale studies are necessary, especially in patients with haematological disorders, homosexual individuals and drug users.

Adolescent↗

Epidemiology of root surface caries in patients treated for periodontal diseases.

The prevalence of root surface caries was estimated in 83 patients surgically treated for periodontal disease and some relating factors were analyzed. The overall root caries index (RCI) was 6.28%. Anterior teeth in the mandible were significantly less affected than other groups of teeth. Root surfaces, divided into subgroups according to surgical treatment and length of exposure, showed no significant differences in RCI. No correlation was found between DFS-index and RCI. RCI increased with age. Concomitantly in older people more time had elapsed between the periodontal treatment and the present clinical examination. Salivary S. mutans counts and a combination of higher salivary S. mutans and lactobacilli counts were good indicators for the presence of root surface caries.

Adult↗

Quantification of Leishmania-specific T cells in human American cutaneous leishmaniasis (Leishmania braziliensis braziliensis) by limiting dilution analysis.

Limiting dilution analysis was used to estimate the frequency of Leishmania-specific T cells from the peripheral blood of 18 human cases of American Cutaneous Leishmaniasis (ACL). Sixteen patients had localized cutaneous leishmaniasis (LCL) and two were recovered LCL patients. In 10 patients with active disease and in two with healed lesions the Leishmania-specific T cell frequencies ranged from 1/10(5) to 1/10(3). In six patients no proliferation was detected after 21 days of cell culture. This finding points to very low precursor frequencies in the peripheral blood of these patients. A significant correlation was found between the two groups with low or high Leishmania-specific T cell frequencies and the lymphoproliferative responses to leishmanial antigens. The majority of the blast-like Leishmania-specific T cells showed a helper/inducer (CD4) phenotype.

Adolescent↗

Non-Hodgkin lymphoma in Jamaica and its relation to adult T-cell leukemia-lymphoma.

Of 95 patients consecutively diagnosed with non-Hodgkin lymphoma, 52 (55%) had antibodies to human T-cell leukemia-lymphoma virus, type I. Antibody positivity was strongly associated with skin involvement, leukemia, and hypercalcemia (p less than 0.02). Two patients had systemic opportunistic infections. Neither meningeal nor lung infiltration was detected, and lymph node infiltration was diffuse in all patients. Of 36 patients who received immunophenotypic classifications, 30 had diseases that affected the T-cell system, and the cells of all tested patients with these diseases showed the helper/inducer (T4) phenotype. Twenty-seven of these thirty-six patients were found to have adult T-cell leukemia-lymphoma, and of the 27, 24 had antibodies to HTLV-I. The median duration of survival in patients with adult T-cell leukemia-lymphoma was 17 weeks, but a subgroup of 9 patients had indolent courses and a median survival of 81 weeks, which suggests that the disease has differing expression with courses that range from smoldering and indolent to acute and rapidly fatal. Hypercalcemia was the most important prognostic determinant of adult T-cell leukemia-lymphoma.

Adolescent↗

The residual effect of treatment with ivermectin after experimental reinfection with nematodes in calves.

The residual effect of treatment with ivermectin after experimental reinfection in calves was tested. Twenty-four calves were divided into 6 groups of 4 calves each. All calves received a primary infection of 50,000 larvae of both Ostertagia ostertagi and Cooperia oncophora and 1000 Dictyocaulus viviparus larvae. Calves of group 1 remained untreated, and all other calves were treated 21 days after primary infection (0.2 mg/kg injected subcutaneously). Calves of groups 1 and 2 were slaughtered 7 days later. Calves of groups 3-6 were reinfected with the same number of larvae 3 days, 1, 3 and 6 weeks after treatment respectively. Slaughter was 21 days after reinfection. Based on post-mortem worm counts the efficacy of ivermectin after primary infection was 99.7% for O. ostertagi, 95.1% for C. oncophora and 100% for D. viviparus. A residual effect was present for at least one week, but could not be observed 3 weeks after treatment.

Animals↗