Relapse of acute promyelocytic leukemia with PML-RARalpha mutant subclones independent of proximate all-trans retinoic acid selection pressure.

Relapse of acute promyelocytic leukemia (APL) following all-trans retinoic acid (ATRA) therapy has been associated with the acquisition of mutations in the high-affinity ATRA binding site in PML-RARalpha, but little information is available about the selection dynamics of the mutation-harboring subclones. In this study, 6/18 patients treated with sequential ATRA and chemotherapy on protocol INT0129 relapsed with complete replacement of the nonmutant pretreatment APL cell population by a PML-RARalpha mutant subclone. Two patients relapsed in proximity of ATRA treatment; however, in four patients there was a 6-48 month hiatus between the last ATRA treatment and relapse. The mutant subclones were not detectable in samples tested > or = 3 months before relapse at > or = 1 in 10(2) (10(-2)) sensitivity. In one patient, a functionally weak mutation was detected at 10(-4) sensitivity before therapy but only limited pre-relapse enrichment of the mutant subclone was observed on subsequent ATRA therapy. These results indicate that proximate ATRA selection pressure is frequently not the main determinant for the emergence of strongly dominant PML-RARalpha mutant subclones and suggest that APL subclones harboring PML-RARalpha mutations are predisposed to the acquisition of secondary genetic/epigenetic alterations that result in a growth/survival advantage.

[Multiple sclerosis--studies of the correlations between selected parameters of immune response and the clinical course of the disease]. / Stwardnienie rozsiane--badania nad korelacja miedzy wybranymi parametrami odpowiedzi immunologicznej a przebiegiem klinicznym choroby.

In the paper the following immune response parameters were analyzed: number of leucocytes in the cerebrospinal fluid, IgG index, presence and number of oligoclonal IgG bands. The correlation between these parameters and between the parameters and clinical course of multiple sclerosis was studied. Oligoclonal bands were present in the cerebrospinal fluid in 92% cases of MS, and that was the most frequent abnormality among immune response parameters studied. There was a correlation between IgG index, number of leucocytes in the cerebrospinal fluid and number of oligoclonal IgG bands in patients with relapsing-remitting course of the disease. We did not find any statistical differences between the number of leucocytes in the cerebrospinal fluid, the frequency of pleocytosis and the type of the disease, relapsing remitting or chronic progressive. The type of the disease, its duration and number of relapses did not significantly influence the IgG index values and number of IgG oligoclonal bands in the cerebrospinal fluid.

[Comparative epidemiologic studies of multiple sclerosis and cancer of the large intestine in several provinces of western Poland]. / Porównawcze badania epidemiologiczne stwardnienia rozsianego i raka jelita grubego na terenie kilku województw zachodniej Polski.

A trial was made of finding a correlation between the incidence and prevalence of multiple sclerosis and large bowel carcinoma in several microregions (communities and areas of the former counties). The following conclusions have been reached. No correlation was found between the incidence of multiple sclerosis and large bowel carcinoma in these studied areas. A positive correlation was demonstrated between the prevalence of multiple sclerosis and large bowel carcinoma in the areas corresponding to former counties but not in communities. Since the latter index is of much lower importance for the estimation of the frequency of malignant neoplasms there is no reason to assume the existence of one or several common aetiologic factors of multiple sclerosis and large bowel carcinoma determining local differences in the frequency of these diseases.

Therapeutic trials of multiple sclerosis and intrathecal IgG production.

In our clinical trial we have compared the effect of high doses of prednisone, ACTH alone or ACTH and cyclophosphamide on plasma and CSF albumin and IgG levels. We have found that the treatment with high doses of prednisone is more effective in the suppression of CNS IgG synthesis than ACTH, or cyclophosphamide. However the significance of this immunological phenomenon in the pathogenesis of MS is a very complex problem, since we have not observed any correlation between the depression of the intrathecal IgG synthesis and clinical results of MS treatment.

[Further epidemiological studies of primary neoplasms of the nervous system in western Poland]. / Dalsze badania epidemiologiczne pierwotnych nowotworów ukladu nerwowego w zachodniej Polsce.

In West Poland with population on the day of the evaluation of 3,097 thousand the incidence of primary neoplasms of the nervous system was calculated in 5 large administration units (provinces) and in 224 smaller units (communities). The testing of the hypothesis of the equal distribution in the communities demonstrated differences, and in 10 of them this incidence was significantly higher above the mean. The main conclusion of the study is that nervous system neoplasms, 90% of which were located intracranially in our material may occur in foci or clusters of clinical as well as statistical significance.

On the fine structure of the distribution of primary nervous system neoplasms in Western Poland.

The incidence rates of primary nervous system neoplasms in 5 districts (large administrative units) of Western Poland with a relatively homogeneous health care system but some contrasts in economic activity, as well as in 224 communes (smallest administrative units) located within these 5 districts, with a total population of 3,097,000 were estimated on the appointed day (31.12.79). Testing the hypothesis, assuming a homogeneous distribution of nervous system neoplasms over the region under investigation, that the incidence rates were distributed as a Poisson variable has revealed a focal distribution of these tumours; in 15 communes the frequency was higher than 9.0 and deviated from the remainder in the 5% right tail of the distribution. The main conclusion from the presented results was that tumours of the nervous system, of which 90% were intracranially located, may occur in clusters or foci, and this could prove to be of clinical as well as statistical import.

[Primary tumors of the nervous system in the light of an epidemiologic analysis]. / Primäre Tumoren des Nervensystems im Licht einer epidemiologischen Analyse.

On a territory of 5 districts of western Poland with 3.097 thousands of inhabitants the annual incidence rates per 100 thousands of population as well as the prevalence rates of primary neoplasms have been determined. The results of our investigation have shown that multiforme glioblastomas and astrocytomas occurred in the investigated population with the highest annual incidence rates, whereas the highest prevalence rates were found for hypophyseal adenomas, to be followed by astrocytomas, meningiomas and glioblastoma multiforme. The obtained results are critically discussed and compared with epidemiological data presented by other authors who based on records from neurosurgical departments and autoptic sections, it is concluded that the presented results do reflect objectively the epidemiological situation of Poland.

Myelin associated glycoprotein (MAG) in Wallerian degeneration of the optic nerve.

The content of myelin associated glycoprotein (MAG) was studied in the rabbit optic nerves undergoing Wallerian degeneration after ophthalmectomy . MAG was estimated according to the method described by Matthieu and Quarles (1973). The results of the studies demonstrated only negligible changes in the content of MAG in the course of central Wallerian degeneration. These experiments do not support the assumption that the periaxionally localized MAG of the central myelin is as a rule seriously involved in subcellular mechanisms functioning in early stages of central demyelinating processes.