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Biomedical subjects

J Knop

Publications and source records attributed to J Knop.

At least 163 records · Page 9Linked to original sources

Pattern reversal visual evoked potential among men at risk for alcoholism.

The biological sons of male alcoholics, deemed to be at high risk (HR) for the development of alcoholism, were compared to control males, aged 18 to 21, using measures of the visual evoked potential elicited by checkerboard pattern reversal. Overall, the HR and control groups were not distinguished on the basis of visual evoked potential measures acquired from the occipital scalp region; however, when comparisons were restricted to right-handed subjects, the HR subjects showed more symmetry in a positive component with approximate latency of 242 ms compared with control subjects. The results are discussed in relation to hemispheric differences and alcoholism.

Adolescent↗

[Scintigraphic follow-up of osteosarcoma during neoadjuvant chemotherapy. Results of the cooperative osteosarcoma study of the Society for Pediatric Oncology].

The response of osteosarcomas to preoperative chemotherapy as measured by quantitative 99mTc-diphosphonate scintigraphy was compared with the amount of tumor cell destruction found histologically in the resected specimens. 3-phase bone scintigraphy, with determination of tumor/non-tumor (T/NT) ratios, allowed accurate prediction of tumor response in 28 of 30 tumors (accuracy = 93%) after completion and in 10 of 12 osteosarcomas (83%) at the half-way stage of preoperative chemotherapy, when only those tumors were evaluated which showed convergent changes of T/NT ratios in the perfusion and the mineral phase. At the half-way stage, however, evaluation of chemotherapy effects was complicated in 12 of 23 osteosarcomas by diverging T/NT ratios. In contrast, quantification and mapping of the tumor plasma volume and 99mTc-diphosphonate clearance on parametric images predicted correctly the histological tumor response to chemotherapy in 10 of 11 tumors (91%) after completion and in all 11 cases (100%) at the half-way stage.

Adolescent↗

Immunohistochemical demonstration of migration inhibitory factor (MIF) in experimental allergic contact dermatitis.

The kinetics of appearance of MIF+ cells was investigated in experimental contact dermatitis using a monoclonal antibody (7D10) against murine MIF which was reacted with cryostat sections of tissues and detected by the indirect immunoperoxidase test. Four groups of BALB/c mice were investigated: (1) sensitized with 2,4-dinitrofluorobenzene (DNFB); (2) unsensitized controls; (3) tolerized; (4) unsensitized. A challenge dose of DNFB was applied to the ear of animals of groups 1-3 and of croton oil to those of group 4. Three phases could be distinguished in group 1: (a) an initial vascular and exudative reaction; (b) an early cellular phase; and (c) a late cellular phase. At zero time rarely any T lymphocytes (Lyt 1+; Lyt 2+) were seen in all four groups. Within less than 30 min venous endothelial cells became strongly MIF+. This was followed by an influx of monocytes/macrophages reaching a maximum of 72 h in group 1 and a slight peak at 12 h in groups 2 and 3. At 16-24 h in all groups the endothelial reaction weakened while many 7D10+ macrophages appeared in group 1. By double-labelling it was shown that lymphocytes were 7D10-. The influx of lymphocytes, part of which carried the T cell receptor, began at 12 h, reaching a maximum at 72 h in group 1. In groups 2 and 3 only a weak lymphocytic infiltrate developed which declined at 24 h. Group 4 developed an inflammatory reaction after the initial phase with similar kinetics as in group 1. The data suggest that an immune inflammatory reaction is preceded by a nonspecific reaction of the vascular endothelium and the mononuclear phagocytic system and that MIF is playing a central role in these events.

Animals↗

Selective inhibition of the generation of T suppressor cells of contact sensitivity in vitro by interferon.

The T suppressor (Ts) cell response in contact sensitivity is preferentially inhibited by murine interferon-alpha, beta (IFN-alpha, beta) in vivo. Previous studies in vivo have suggested that IFN exerts its effect directly on the Ts subpopulation rather than through an effect on antigen-presenting macrophages. Nevertheless, the mechanism of this selective blockade remained unclear. To better define the mechanism(s) of inhibition of suppression by IFN-alpha, beta, we determined whether IFN acted on lymphocytes, macrophages, or both. Antigen-specific T effector cells of delayed-type hypersensitivity (TDH) and Ts cells were induced in vitro by co-culture of spleen lymphocytes with bone marrow-derived antigen-presenting macrophages (BM-MA) pulse-labeled with 2,4-dinitrobenzene sulfonate (DNBSO3). TDH or Ts activity was demonstrated by transfer of the lymphocytes into naive recipient BALB/c mice after 3 days of culture. BM-MA cultured for 5 to 7 days (BM-MA d5-7) before labeling preferentially activated TDH cells (Thy-1+, Lyt-1+2-); 10- to 14-day-old BM-MA (BM-MA d10) induced Ts cells (Thy-1+, Lyt-2+), as previously shown. Treatment of the spleen lymphocyte suspension with pure mouse IFN-alpha, beta at a dose of 10(3) U/10(8) cells completely blocked the induction of Ts cells but had no effect on the induction of TDH cells. Pretreatment of the antigen-presenting BM-MA for 24 hr with IFN (10(2) U/3 X 10(5) cells) had no effect on the induction of Ts and TDH cells. Cultivation of lymphocytes on a DNP-BM-MA d6 monolayer did not result in the induction of Ts cells; however, in the presence of a goat anti-murine IFN-alpha, beta antibody, Ts cells were induced. This finding indicates that the spontaneous release of IFN-alpha, beta in those cultures prevented the induction of Ts cells. These results confirm our previous observation that Ts cells are more easily blocked by IFN-alpha, beta than TDH cells, and demonstrate that IFN affects the Ts subpopulation not via modulation of the antigen-presenting macrophages. IFN-alpha, beta-producing, antigen-presenting, or accessory cells may therefore prevent the activation of this type of Ts cell.

Animals↗

Histomorphometric changes of osteosarcoma after chemotherapy. Correlation with 99mTc methylene diphosphonate functional imaging.

An investigation to correlate histologic changes in 12 osteosarcoma specimens from patients undergoing chemotherapy was performed using functional images of regional 99mTc methylene diphosphonate (MDP) plasma clearance rates assessed from dynamic bone scintigraphies taken during chemotherapy. Residual tumor cell viability was determined by microscopic examination of multiple thin sections from surgical specimens and quantitated by histomorphometry. Regions that showed decreases in 99mTc MDP plasma clearance of more than 20% were associated with areas of necrotic tumor, and regions that showed absent decline or increasing clearance rates were associated with high residual cell viability and incomplete response to chemotherapy. Therefore, functional bone scintigraphy allows an objective presurgical assessment of tumor response to chemotherapy.

Adolescent↗

Different cellular reaction patterns of epidermal Langerhans cells after application of contact sensitizing, toxic, and tolerogenic compounds. A comparative ultrastructural and morphometric time-course analysis.

BALB/c mice were treated with the irritants croton oil (0.5%, 20%), sodium lauryl sulfate (15%), and benzalkonium chloride (25%), the contact sensitizers 2,4-dinitrofluorobenzene (DNFB, 0.3%) and picryl chloride (PCl, 1%), and the tolerogen 2,4-dinitrothiocyanatebenzene (DNTB, 2%). All irritants used produced degenerative alterations of Langerhans cells (LCs). After application of 0.5% croton oil, however, this degeneration was preceded by an activation of the cells with increased number of mitochondria and enlargement of nuclei. The DNFB and PCl application in sensitizing doses to nonsensitized animals resulted in a cellular activation similar to that observed for 0.5% croton oil. In addition, these LCs showed enhanced adsorptive endocytosis as demonstrated by increased numbers of Birbeck granules and coated vesicles. The endocytotic activity was more pronounced in DNFB-sensitized animals. The DNTB at a concentration that induced tolerance to DNFB did not cause either cellular or endocytotic activation of LCs. These results demonstrate that the contact sensitizers DNFB and PCl induce characteristic cellular reaction patterns of LCs, which may be related to their sensitizing property.

Animals↗

A prospective study of young men at high risk for alcoholism. Social and psychological characteristics.

In a prospective longitudinal study of alcoholism, we applied the high-risk method using a Danish birth cohort (9125 consecutive deliveries, 1959 to 1961). From the cohort, 134 sons of alcoholic fathers (high-risk group) and 70 matched controls without parental alcoholism were selected for study. Extensive data were collected in a multidisciplinary etiologic approach. We report the social and psychological characteristics from a "premorbid" assessment when the subjects were 19 to 20 years old. The high-risk group reported more disrupted familial conditions during childhood than the control group. Both groups had a drinking pattern similar to that of the general Danish population at the same age. No alcoholic subjects were found. The high-risk group was characterized by poor verbal ability and impulsive behavior. We plan a follow-up examination of the sample.

Adult↗

Ultrastructural morphometry of epidermal Langerhans' cells: introduction of a simple method for a comprehensive quantitative analysis of the cells.

The ultrastructural demonstration of Birbeck granules is the most exact morphological marker for Langerhans' cells (LCs). We have developed a specific ultrastructural morphometric technique that enables quantitative evaluation of the numerical and volume density of LCs as well as quantification of cellular details. Evaluation of normal human skin of the hand and lower buttock showed that the epidermis of the hand contained a significantly higher numerical and volume density of LCs. At the cellular level, these LCs exhibited signs of increased metabolic activity, as reflected by the morphometric data of the nucleus, mitochondria, Golgi area, and Birbeck granules. The present technique thus allows functional characterization of LCs at the morphological level.

Adult↗

Inhibitory effects of interferon-gamma on the T suppressor cell circuit in contact sensitivity.

The effects of a partially purified, splenocyte-derived murine interferon (MuIFN-gamma N) and a recombinant IFN-gamma (MuIFN-gamma R) on the T suppressor pathway and on the T effector cells of delayed type hypersensitivity were investigated in a 2,4-dinitrofluorobenzene contact sensitivity model. Various T cell subpopulations, suppressor T cells of afferent and efferent types, and an auxiliary T suppressor cells as well as a T effector cell of delayed type hypersensitivity were induced and the functions assessed in transfer experiments. Confirming the results of earlier experiments obtained with IFN-alpha, beta, the MuIFN-gamma N preparation and the rec. MuIFN-gamma R: enhanced the decreased response in animals sensitized with an antigen overload to an optimal response; inhibited the afferent-acting T suppressor cell in vivo and in vitro; inhibited the Ts-eff response; blocked the auxiliary T suppressor cell response after intravenous injection to recipients of Ts-eff cells on day 0 and 1; and did not suppress the activity of the T effector cell of delayed type hypersensitivity in vivo and in vitro (the MuIFN-gamma R was not tested). We conclude that IFN-gamma preferentially inhibited the T suppressor cell circuit of contact allergy. These results are similar to our observations on the inhibitory effects of a pure interferon-alpha, beta on the regulatory T suppressor cell circuit in contact allergy. Selective suppression of different T subpopulations by IFN-gamma may be an important regulatory mechanism in delayed type hypersensitivity.

Animals↗

[Comparative x-ray and nuclear medical studies of osteosarcomas to evaluate the effectiveness of preoperative chemotherapy].

In 16 patients with a long bone osteosarcoma treated after the therapy regimen of COSS 80/82 (Cooperative Osteosarcoma Study) the tumour response to preoperative chemotherapy was assessed by conventional roentgenograms (plain films, tomograms, angiograms). The histological grade of regression determined in the operative specimen was used as a reference for the extent of tumour devitalisation. By their different typical roentgenological course the osteosarcomas with a very good and those with a rather poor response could be correctly identified (100%). On following the clinically used differentiation between "good responders" (histological grades I to III) and "poor responders" (grades IV to VI) the corresponding classification of these tumours by roentgenograms and functional scintigraphic imaging was found to be correct in 94% of the cases. The coincidence of the correct as well as the false results in both radiological methods was as high as 100% if those osteosarcomas showing only a "medium response" in their roentgenograms were added to the clinical group of good responders. There were no fundamentally discrepant results obtained by each of the two radiological techniques. With the combined workup of the roentgenological and the scintigraphic material any incorrect preoperative estimation of tumour regression with a harmful influence on therapy (date and type of surgery, mode of postoperative chemotherapy) could be avoided.

Adolescent↗

Leukapheresis in the treatment of cutaneous T-cell lymphomas.

In six patients with cutaneous T-cell lymphomas (CTCL), the effect of leukapheresis (LPH) on the disease and on various immunological and haematological parameters was investigated. Enriched mononuclear cells were removed by continuous centrifugation leukapheresis from the peripheral blood of the patients. A profound and longlasting effect was seen in one patient with the Sézary variant; a moderate response was seen in two other Sézary patients. No benefit was observed in two patients with more aggressive leukaemic disease, and one patient with plaque stage MF responded on two occasions. No limiting side effects were recognized and no consistent changes of immunological or haematological parameters were observed after LPH.

Aged↗

Subjective and objective measures of response to alcohol among young men at risk for alcoholism.

Biological sons of alcoholic men constitute one group at high risk (HR) for the development of alcoholism. A low dose of alcohol (0.5 g/kg) was administered to HR and control subjects. Measures based on self-ratings, an observer's assessment and visuomotor performance were used to compare the HR and control subjects before and after alcohol administration. Results showed HR subjects' self-ratings of intoxication and somatic symptoms were significantly lower than those of control subjects after alcohol administration. Measures based on an observer's assessment of the two groups did not distinguish them, but one measure of visuomotor performance did. Because the HR and control subjects did not differ in self-reported alcohol consumption or blood alcohol levels acquired in this study, it appears unlikely these factors could account for the differential responses to alcohol administration in HR and control subjects.

Alcohol Drinking↗

Effect of cyclosporin A on the T-effector and T-suppressor cell response in contact sensitivity.

The effect of cyclosporin A (CyA) on the induction, expression and regulation of the immune response to the contact sensitivity agent 2,4-dinitroflouro-benzene, (DNFB) has been studied in BALB/c mice. CyA was administered orally during the sensitization phase or during the elicitation phase. The following results were obtained. CyA administered orally during the sensitization phase at a high dose resulted in a reduction of the contact sensitivity response. Feeding lower doses had no effect on the ear swelling response. CyA inhibited the ear swelling response if administered during the elicitation phase. In transfer experiments it was shown that the induction of the T-effector cell of delayed hypersensitivity (TDH) was insensitive to the suppressive action of CyA, while the effector function of this T-cell subpopulation was CyA-sensitive. T-suppressor (TS) cell response was studied in animals by inducing tolerance through epicutaneous application of an allergen overload and by transfer of TS cells induced by intravenous injection of the contact sensitizer. Tolerance induction in vivo and TS-cell induction and function were inhibited in CyA-treated animals.

Animals↗

Premorbid assessment of young men at high risk for alcoholism.

The high-risk paradigm has been applied to a group of sons of alcoholic fathers and a control group without parental alcoholism. The sample is selected from a Danish birth cohort (1959 to 1961) including 8949 consecutive deliveries. A multidisciplinary assessment was undertaken when the subjects were 18 to 19 years old. The over-all results from this premorbid phase of the longitudinal study are presented. Items such as impulsivity, restlessness, and specific school problems are characteristic for the high-risk group and may be of predictive importance. A follow-up assessment of the sample is planned during the next five to ten years.

Adolescent↗

A prospective study of young men at high risk for alcoholism: school behavior and achievement.

From a large consecutive birth cohort in Denmark, 134 sons of alcoholic fathers (high-risk group) and 70 matched controls were selected for a prospective longitudinal study of alcoholism. A premorbid multidisciplinary assessment was conducted at age 19-20. Data were derived from three sources: a social worker interview, a psychopathological interview that also collected information about current drinking pattern, and a questionnaire sent to teachers. The high-risk group reported having experienced a more disturbed school career, and were rated by their teachers as having been more impulsive and as having had poorer verbal proficiency. These factors may be predictive of future alcoholism.

Achievement↗