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Biomedical subjects

Y Kock

Publications and source records attributed to Y Kock.

8 recordsLinked to original sources

In vitro suspension culture reactions to 1,25 dihydroxyvitamin D3 in relation to bone marrow morphology and prognosis in patients with myelodysplastic syndromes.

Thirty-four patients with MDS or AML following MDS were studied with regard to survival, peripheral blood values and bone marrow morphology. The effects of 1,25 dihydroxyvitamin D3 (D3) on differentiation (NBT positivity) and proliferation (3H-thymidine incorporation) were studied in suspension cultures of bone marrow cells. Twelve bone marrow donors served as controls. Normal cells showed spontaneous differentiation in vitro, but only 2/12 were induced to differentiation by D3. Myelodysplastic cells did not differentiate spontaneously, but cells from 18/34 patients differentiated after incubation with D3. Normal cells showed increased proliferation, myelodysplastic cells showed a heterogeneous response and leukemic cells reacted with decreased proliferation after D3 incubation. Poor survival was associated with low platelet counts, high percentage of bone marrow blasts (BM blast %), low spontaneous in vitro proliferation and absence of hypogranulation of myeloid cells. Platelet counts and hypogranulation retained their predictive value in a multi-variate analysis. Progression to AML was predicted by a high BM blast % and low scores for erythroid and total dysplasia. In conclusion, the pattern of in vitro proliferation showed prognostic value while the pattern of vitamin D3-induced differentiation failed to correlate to other parameters. An estimation of bone marrow dysplasia can be used to predict the development of AML. Our results add to the information about the biology of MDS and may be important for the evaluation of therapeutic trials.

Acute Disease

A predictive model for the clinical response to low dose ara-C: a study of 102 patients with myelodysplastic syndromes or acute leukaemia.

The response to treatment with low-dose ara-C was studied in 102 consecutive patients; 79 with myelodysplastic syndrome (MDS) and 23 with acute myelogenous leukaemia (AML) following MDS. The aim was to find variables that could predict the response to treatment. All patients had clinical symptoms related to cytopenia. Peripheral blood values, bone marrow morphology histology and chromosomes were analysed before the start of treatment. The median survival of the patients was 9 months and a poor survival was predicted by advanced age, low platelet counts, the presence of pseudo-Pelger morphology and > or = 2 chromosomal aberrations. Thirty patients (29%) responded with either a complete remission or a significant increase in haemoglobin level. For the remaining 71%, the treatment was ineffective and in some cases hazardous. The factors associated with a poor response to treatment could be divided into two groups: one included low platelet counts and the presence of chromosomal aberrations, both signs of progressive MDS with a short survival, and the other comprised morphological findings, indicating ineffective haemopoiesis. Patients with platelet counts > 150 x 10(9)/l had a response rate of 55% compared to 23.5% in patients with subnormal platelet counts. Logistic regression identified low bone marrow cellularity, absence of ring sideroblasts and < 2 chromosomal aberrations as predictors of a favourable response in patients with platelet counts < 150 x 10(9)/l. These factors and the platelet count were combined in a predictive model which can divide patients into three groups with different probabilities of response: a favourable group, 38.6% of the patients, with a response rate of > 50%, an intermediate group, 32.7% of the patients, with a response rate of 24%, and an unfavourable group, 28.7% of the patients, with only 3% responses. While low-dose ara-C is an effective treatment for some patients, it is ineffective and hazardous for others. We present a model that can facilitate therapeutic decision making in two-thirds of patients with MDS and MDS-AML by identifying patients who should not be treated with low-dose ara-C as well as patients with a relatively high probability of response.

Aged

Studies on the distribution of abnormal cells in cytological smears. VII. Cervical brush versus plastic and wooden spatulas.

A model system of exfoliated normal human cervicovaginal squamous cells, exfoliated rodent tumor cells, and acellular, viscous, mucuslike material was used to investigate cell deposition on smear preparations made with three different instruments: plastic spatulas, wooden spatulas, and brush-tipped collectors. The total number of exfoliated cells and the total number of tumor cells present within the randomly distributed holes were then recorded for 41 smear preparations. For smears done with the brush, a total of 47,146 exfoliated cells were recorded; with wooden spatulas, 4517 cells; and with plastic spatulas, 7648 cells. When the brush was used, 6905 tumor cells were recorded. When wooden or plastic spatulas were applied, 563 and 1132 tumor cells were found, respectively. Thus, the brush yielded 12.2 and 6.1 times more tumor cells than plastic and wooden spatulas, respectively.

Cervix Uteri

Viability of the human cervical epithelium with dysplasia and carcinoma in situ.

Autoradiograms of histologic slides of 58 human cone specimens with dysplasia and carcinoma in situ were analyzed after tissue samples were incubated with labeled RNA precursors. Both the vertical and lateral distributions of labeled cells were rather uniform in the major part of the epithelium, which suggested that the tissue remained metabolically active during incubation. Only the uppermost epithelial cells in heavily labeled areas were devitalized as deduced by the morphologic appearance of the cells, the absence of labeling in the cells, the trypan blue exclusion test, and the trypsin digestion test. The viability of large epithelial areas suggested that the previously reported focal distribution of proliferating and nonproliferating areas in the cervical epithelium is a genuine phenomenon and not the result of focal epithelial devitalization acquired during incubation.

Carcinoma in Situ

Big cones and little cones.

To investigate whether the amount of tissue removed at conization could influence the frequency of inadequate excision of cervical atypias, 354 cone specimens were measured. The data indicate that the frequency of lesions incompletely removed at conization increased with decreasing size (ie. length and volume) of the specimen. The parameters influencing the detection of epithelial atypias at the surgical margin of the specimens are discussed. A plea is made for international standardization in reporting results of conization (size of cone and number of sections) in order to permit objective comparison between clinics of the results of the conization procedure.

Carcinoma in Situ

Influence of the size of cone specimens on postoperative hemorrhage.

To investigate whether the amount of the tissue removed at conization could influence the frequency of postoperative hemorrhage, the size of 221 cone specimens was measured in two different series. The 119 patients in the first series were operated upon mainly during 1972 and the second series of 102 patients mainly during 1973. The cones in Series II were empirically reduced following the technique proposed by Crisp and associates. Actual measurements demonstrated that the specimens in Series II were smaller than in Series I. The frequency of bleeding following conization was 4 per cent in the second series but as high as 21 per cent in the first series. Postconization hemorrhages, however, were unrelated to the size of the individual cone specimens in the different series. The operative technique used in Series II appears to be responsible for the decrease in the amount of postconization hemorrhages.

Adult

Alterations in erythropoiesis preceding leukemia.

An attempt was made to study preleukemic changes in bone marrow cell proliferation. Seven patients with hypercellular marrows and aregenerative anemia were studied. Five of them could be followed to autopsy, several years after the kinetic studies; all died with a picture of leukemia. Total bone marrow cell numbers, erythroblast generation times, and erythrocyte production were estimated with 59Fe. Despite hypercellularity, the total erythroblast number was not significantly increased. Erythrocyte production and life span were both decreased, and erythroblast generation time were significantly longer than normal.

Adult

Cell proliferation of the normal esophagus of mice harbouring a squamous cell neoplasia in the uterine cervix.

Some human tumors have been found to induce proliferative lesions in the squamous epithelium in organs remote from the primary tumor. This phenomenon was explored in the present animal model. After a single injection of 3H-thymidine, the proportion of DNA synthesizing basal and parabasal esophageal cells as well as the pace of intraepithelial cell migration was assessed in 124 C57Bl mice. The uterine cervix of 57 animals had been painted topically with 3,4 benzo(a)pyrene for 5 months, or with the vehicle acetone (44 animals), while 23 animals remained untreated. Groups of animals were killed from 8 hours to 10 days following a single pulse labelling. The proportion of DNA synthesizing basal and parabasal esophageal cells and of their daughter cells (as deduced by observations at various time intervals) was similar in animals harbouring neoplasias of the uterine cervix, in those treated with benzo(a)pyrene but having histologically normal cervical epithelium, in acetone treated as well as in untreated controls. Thus, in the model used herein, we failed to demonstrate increased cell proliferation in the esophageal mucosa of animals having a squamous cell neoplasia in the uterine cervix. The method appears, however, sensitive enough to register ongoing cell proliferation patterns and will be applied to the study of other experimentally induced tumors.

Animals