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J Willems

Publications and source records attributed to J Willems.

At least 73 records · Page 4Linked to original sources
PubMed1988

Importance of MHC antigen expression on solid tumors in the in vitro interaction with autologous blood lymphocytes.

In 54 patients with lung and 14 with ovarian carcinomas the quantitative variations of the major histocompatibility complex (MHC)-determined class I and class II antigens of the tumor cells were related to their in vitro interaction with blood lymphocytes, to the lymphoid infiltration of the tumors, and to the metastatic state of the disease. The tumor cell-lymphocyte interaction was measured by the proliferative response in mixed lymphocyte tumor cell culture and by the cytotoxic activity of the lymphocytes. The results showed that (1) none of the 23 tumors from patients with disseminated disease were lysed; (2) class I-negative tumors were not damaged; (3) lymphoid infiltration was present in a higher proportion of class II-positive tumors; and (4) both MHC-positive and -negative tumors were found among the disseminated tumors. The requirement of class I expression in the lytic interaction substantiates our earlier conclusion concerning the cytotoxic T lymphocyte nature of lymphocyte-mediated auto-tumor lysis. The lack of auto-tumor lysis in patients with metastases suggests impairment of lymphocyte function in advanced stages of the disease.

Adenocarcinoma↗
PubMed1988

Nephrogenic diabetes insipidus: close linkage with markers from the distal long arm of the human X chromosome.

Ten families with nephrogenic diabetes insipidus (NDI) have been analysed for restriction fragment length polymorphisms (RFLPs). A search for linkage was performed using various chromosome-specific single-copy DNA probes of known regional assignment to the human X chromosome. Close linkage was found between the disease locus and the markers DXS52, DXS15, DXS134 and the F8 gene. This result assigns the NDI gene to the subtelomeric region of the long arm of the X chromosome. The regional localization of the gene by the identification of closely linked markers should have repercussions for genetic counselling and prevention in NDI families.

Alleles↗
PubMed1988

Enhanced oxygen metabolism of peritoneal macrophages in the presence of murine neuroblastoma cells is partly caused by enkephalins.

A bioluminescent technique was used to show that murine neuroblastoma (NB) cells or cell-free extracts (H variant) were able to enhance the release of reactive oxygen intermediates (ROI) from peritoneal macrophages in vitro. L-variant NB cells were ineffective. Physiological concentrations of met-enkephalin produced the same effect in vitro but not leu-enkephalin. When both H- and L-variant cells, or their extracts, were incubated together with macrophages, ROI production was not increased. Similar findings were detectable when met- and leu-enkephalin were cultured together with macrophages. In vivo, preliminary studies gave the same results. The concentration rate of met- to leu-enkephalin was higher in H-variant than in L-variant NB cells. We conclude from our results that met-enkephalin can enhance the release of ROI from peritoneal macrophages. The difference in the effects produced by the H and L variants is due to differences in the concentrations of enkephalins released.

Animals↗
PubMed1988

Linkage of X-linked nephrogenic diabetes insipidus with DXS52, a polymorphic DNA marker.

In five families with X-linked nephrogenic diabetes insipidus (NDI), linkage studies with the DNA marker DXS52, defined by probe St14, have shown no recombination with a maximum combined lod score of 6.40. These results assign the NDI gene to the subtelomeric region of the X chromosome long arm. This finding should facilitate identification of carriers and should also be helpful in finding the NDI gene itself.

DNA↗
PubMed1987

Cellular immunity changes caused by LDH virus: analogy with observations of neuroblastoma-bearing mice.

Evidence is presented that LDH virus infection of mice results in drastic changes in several immune activities. Serum IFN titer and splenic NK activity are increased during the acute phase of infection. NK stimulation is mediated by IFN-alpha,beta since injection of an antibody against murine IFN-alpha,beta is able to abolish the effect. IL-2 production is inhibited throughout the study period following injection of LDH virus (14 days), although a partial recovery is observed during the second week. Similarly, IL-2 receptor expression and MLC responsiveness are suppressed. This suppression lasts for 2 and 7 days respectively after injection. Addition of recombinant IL-2, but not of indomethacin, to the MLC cultures restores the proliferation rate. Not only proliferation but also cytotoxic cell generation in MLC is diminished during the first week after LDH virus injection. Again, this response is normalized at day 14. Additional observations indicate that LDH virus is present in murine neuroblastoma. This explains some of the previously described effects of this tumor on the cellular immune system of the host.

Animals↗
PubMed1987

DNA flow analysis of soft tissue tumors.

The cellular DNA content of 81 soft tissue tumors was determined by means of flow cytometry and related to conventional histologic classification of the same tumors. Comparison of histologic and cytometric analysis showed that all 23 benign tumors were diploid (normal DNA content), whereas the malignant group included both diploid and aneuploid (abnormal DNA content) lesions. There appeared to be a relationship between tumor grade and ploidy level in that 92% of Grade II, 28% of Grade III, and 11% of Grade IV lesions were diploid. Cell distribution analysis, feasible in 51 cases, disclosed that diploid lesions had a low proportion of S and G2 + M cells and most aneuploid lesions a high proportion, indicating a relationship between ploidy level and proliferative activity. The current study shows that solid mesenchymal tumors may be analyzed by DNA flow cytometry. Regardless of histogenetic type, it appears that benign and low-grade tumors are diploid and high-grade tumors, in general, are aneuploid. As to exceptions, DNA analysis may prove to give information beyond that obtained by subjective histologic interpretation. Thus, adequate follow-up might show that high-grade lesions with a diploid DNA content are associated with a better prognosis than expected from histologic classification.

Aneuploidy↗
PubMed1987

Lysis of autologous tumor cells by blood lymphocytes activated in autologous mixed lymphocyte tumor cell culture--no correlation with the postsurgical clinical course.

Mixed lymphocyte tumor cell cultures (MLTC) were initiated with cells collected at the time of surgery from 62 patients with the following diagnoses: 12 squamous cell carcinoma, 14 adenocarcinoma of the lung, 17 osteosarcomas, and 16 soft tissue sarcomas. The lytic effect generated against autologous tumor cells was tested on the 7th day. These patients had been part of previous evaluation, which revealed that the lysis of autologous tumor cells by freshly collected lymphocytes correlated with the postsurgical clinical course. Patients with long survival exhibited autotumor lysis without previous activation. Blood lymphocytes of about half of the primarily nonreactive patients were stimulated for lytic function in MLTC. However, this parameter showed no correlation with the clinical course.

Aged↗
PubMed1987

Toxicokinetics of methyl paraoxon in the dog.

The toxicokinetics of methyl paraoxon, the active metabolite of the organophosphorus insecticide methyl parathion, were studied in non-anaesthetized dogs after intravenous (2.5 mg/kg) and oral (15 mg/kg) administration of methyl paraoxon. After intravenous administration, distribution and elimination occurred very rapidly and using the data from 5 min post-injection, the plasma concentration versus time curves could be fitted to a one-compartment open model. The mean half-life of elimination was 9.7 min, the average volume of distribution 1.76 l/kg and the average plasma clearance 126 ml/kg/min. After oral administration, peak plasma concentrations were obtained within 3-16 min, and the bioavailability varied from 5 to 71%. The hepatic extraction of methyl paraoxon measured in anaesthetized dogs, was high (70-92%). Comparison of the urinary excretion after intravenous and oral administration in two dogs indicated a gastrointestinal absorption of more than 60%. The kinetics of methyl paraoxon were linear in the dose range tested.

Administration, Oral↗
PubMed1987

The syndrome of hypertension and hyperkalaemia with normal glomerular function (Gordon's syndrome). A pathophysiological study.

A 14-year-old boy with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome) is described. The patient's clinical symptoms consisted of periodic paralysis, slight metabolic acidosis of the proximal type and hypercalciuria. Prostaglandin excretion was normal. Infusion of atrial natriuretic peptide had no effect on electrolyte excretion or glomerular function although a normal increase in cyclic guanosine monophosphate was demonstrated in plasma and urine. This lack of sensitivity to atrial natriuretic peptide offers a new pathophysiological concept in this syndrome. Treatment with hydrochlorothiazide was successful in this case.

Adolescent↗
PubMed1987

Auto-tumor immunity in patients with solid tumors: participation of CD3 complex and MHC class I antigens in the lytic interaction.

In a number of experiments performed with blood lymphocytes of patients, the high density subset lysed autologous tumor cells separated from the surgical specimens. The lysis was abrogated by pretreatment of the effector cells with antibodies (OKT3) directed against the T3 molecule associated with the T cell receptor and by pretreatment of the target cells with antibodies (W6/32) directed against the monomorphic part of the MHC class I antigens. This subset lyses only autologous tumor cells. The selectivity and the characteristics shared with antigen specific cytotoxic T lymphocytes (CTL) suggest that the auto-tumor lysis by the effectors reflects an immune response against the tumor cells. The low density lymphocytes, separated from the blood, can lyse both auto- and allogeneic tumor cell. In the autologous system, incubation of the effectors with the mAb OKT3 had no inhibitory effect and incubation of the targets with the anti W6/32 mAb inhibited their lysis only in some experiments. The nature of the reactivity of the LD lymphocytes remains to be defined. Whether it is similar to the indiscriminative natural killing or whether part of these lymphocytes are antigen(s) specific and exhibit a high avidity interaction with the target remains to be seen. It is possible that both types of target recognition occur since the LD lymphocyte population is heterogeneous.

Aged↗
PubMed1987

Immune response to murine neuroblastoma: effects of in vitro culture of the tumor.

The humoral and cellular immune response of neuroblastoma (NB)-bearing mice has been investigated and shown to be dependent on the treatment of the NB tumor cells before implantation. Established lines and clones derived from the original tumor, as well as C1300 cells passaged in vitro, provoke an immune reaction which differs markedly from the one induced by the original C1300 tumor. Indeed, only the latter induces the formation of high amounts of circulating immune complexes (CIC), is able to trigger peritoneal macrophages in the host and to induce suppression, as shown in mixed lymphocyte cultures. After subculture of the tumor cells in vitro, none of these effects were observed. The pattern of immune response produced by tumor cells grown in vitro can be converted into the original type of response by repeated passaging of the tumor cells in vivo.

Animals↗
PubMed1987

Carcinoma in situ of the vulva. Long term prognosis.

Seventy-four patients with carcinoma in situ (CIS) of the vulva were followed over a 10-year period. The mean age was 52.8 years (range 21 to 90 years). Pruritus was the most common symptom. Forty per cent of the women were asymptomatic. Twenty-three per cent had a history of carcinoma in situ of the uterine cervix. Single lesions of CIS were found in the perineal area in 22 per cent, in the labia major and minor in 23 per cent, and in the clitoris in 7 per cent. Forty-two per cent of the patients had CIS in two or more of those areas. Seven of 74 patients (10%) had previously been irradiated for pelvic malignant tumours. Three women developed invasive squamous cell carcinoma of the vulva, two of them were previously irradiated. All 74 patients were treated surgically in different ways. Out of 38 women with histologically free margins of surgery, 6 had recurrence of dysplasia or CIS.

Adult↗
PubMed1987

NK activity in neuroblastoma bearing mice: in vivo versus in vitro propagated tumor variants.

Two days after inoculation of A/J mice with in vivo propagated C1300 neuroblastoma (NB) cells, a 4-5 fold increase of the splenic natural killer (NK) activity is noticed. A similar rise of NK activity is also displayed by the host lymph node, bone marrow and peritoneal cells, reflecting a general stimulation of NK cells. These effector cells only lyse classical NK target cells. They are of low specific gravity, nylon wool non-adherent and insensitive to anti-Thy treatment, suggesting that they are indeed NK cells. In spite of the ability of in vivo maintained NB cells to increase the NK activity, they are not lysed by NK cells, nor do they have NK-recognizable target structures as demonstrated by competition studies. In contrast with the previously mentioned experiments, NB cells that have been cultured in vitro for at least one week, do not increase the NK activity. During further growth of both tumor variants, the NK activity gradually decreases. In vivo experiments revealed that the presence of a large NB tumor load exerts a negative effect on the induction of active NK effectors. This effect is not due to the intervention of splenic suppressor cells.

Animals↗
PubMed1986

Lysis of autologous tumor cells by high-density lymphocytes is potentiated by the streptococcal preparation OK432 (Picibanil).

In experiments performed with tumor cells isolated from surgical specimens and lymphocytes collected at the time of surgery, tumor cells are often lysed by blood lymphocytes. Some of the effectors are present in the high-density T-cell subset. This population has little or no anti-K562 activity. For the auto-tumor lysis of T cells with high density, CD8-positive cells are mainly responsible. OK432 pretreatment of the effectors potentiates the existing lytic function or induces it in cases in which the cells have no such function. In general, the potentiating effect reflects inherent patterns of cytotoxicity. In contrast to the lysis of autologous tumor cells, cells with low but not high density were induced to lyse K562.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Lysis of autologous tumor cells by blood lymphocytes tested at the time of surgery. Correlation with the postsurgical clinical course.

Lymphocyte-mediated lysis of autologous tumor cells (autologous lymphocyte cytotoxicity ALC) was tested at the time of surgery in 108 patients (46 squamous cell carcinomas of the lung, 25 adenocarcinomas of the lung, 19 soft tissue sarcomas and 18 osteosarcomas). The clinical course of these patients in relation to the test results has been published previously. The group was evaluated again after an extended observation time, now with a mean of 80.2 months (range 36-108). The test was rarely positive in patients with metastasis (2 out of 28 experiments). There was a correlation between the ALC results and the postsurgical clinical course for patients without detectable metastasis in that (1) a negative test was invariably a bad prognostic sign, i.e., all 32 patients with negative ALC died within 3 years (mean survival time 16.1 months). (2) The remission and survival times were longer for the ALC positive patients (p less than 0.001). (3) All 37 individuals who are alive at present without recurrence belong to the reactive group. The ALC results correlated with the clinical course in 88% of patients. The correlation was highest for the groups of soft tissue sarcoma and adenocarcinoma of the lung. There was no correlation between killing of K562 cells and ALC, or between lymphoproliferative response to PHA and ALC reactivity.

Adenocarcinoma↗
PubMed1986

Immune response to murine neuroblastoma: effects of in vitro culture of the tumor. Mitogen and mixed lymphocyte culture responses, interleukin-2 production, suppression and natural killer activity.

The cellular immune response in A/J mice inoculated with in vitro cultured neuroblastoma (NB) cells is completely different from the response obtained after inoculation of in vivo passaged NB cells. Indeed, inoculation of in vivo grown tumor cells leads to a strongly decreased MLC and PHA response of the host spleen cells. This depressed response is not reversed by in vitro addition of indomethacin, but correlates with a low IL-2 production by the spleen cells. In addition, non-specific suppressor cells are present in the spleen and in the peritoneal cavity. The splenic suppressor cells are of low specific gravity and they are nylon wool adherent. The suppressor capacity is not reduced by anti-Thy plus rabbit complement treatment. Another effect of in vivo maintained NB cells is that the natural killer (NK) activity of the spleen cells of the host is increased 4-5 fold 2 days after inoculation of the tumor cells. On the contrary, in vitro passaged NB cells do not induce a reduced MLC and PHA responsiveness, and the IL-2 production of the host spleen cells remains nearly normal. No non-specific suppression can be demonstrated and the NK activity is not augmented 2 days after inoculation. We can conclude that it is very important in which condition tumor cells are maintained when used to study anti-tumor immunity.

Animals↗
PubMed1985

DR antigens expressed on tumor cells do not contribute to the blastogenetic response of autologous T cells.

Tumor cell suspensions prepared from surgical specimens were characterized for cellular composition and reactivity with monoclonal antibodies detecting T lymphocytes, monocytes, and the monomorphic determinants of DR molecules (antigens encoded by the D region of the major histocompatibility complex in man). About half the adenocarcinoma preparations contained tumor cells which expressed DR antigens. Lymphocytes of certain patients were stimulated in vitro by the autologous tumor cells, and this was independent of the expression of DR antigens on the tumor cells. In addition, pretreatment of the stimulator tumor cells with anti-DR Mab (monoclonal antibody) had only marginal effect on their stimulatory potential. In contrast, when the same tumor cells were used as stimulators of allogeneic lymphocytes, proliferation was more often seen with DR-positive tumors and the reaction was often inhibited by the anti-DR Mab treatment. There were exceptions, however, which suggest that other DR antigens not detected by the reagents used may have been expressed on these cells. The allostimulatory capacity of the tumor cells was usually weak and did not occur with all responder lymphocytes. It is important to note that stimulation of autologous lymphocytes could occur with tumor preparations that did not elicit allogeneic response. Thus, the in vitro stimulation of autologous blood-derived T cells by suspensions of unpropagated cells separated from solid tumors reflects the sensitization state of the patients against their tumor cells.

Adenocarcinoma↗