[Evaluation of thyroid cancer morbidity in Warsaw in 1987-1997]. / Ocena zachorowalnosci na nowotwory zlosliwe tarczycy w Warszawie w latach 1987-1997.

The crude and standardized thyroid cancer incidence rates calculated for the period 1987-1997 in Poland increased from 0.5 to 0.9 and 0.5 to 0.8 per 100,000 men, and from 1.8 to 3.6 and 1.4 to 2.8 per 100,000 women. The incidence of the cancer in women in Warsaw doubled during the same period. The upward trend only slightly showed up in the male population of Warsaw. Mortality rates caused by the thyroid cancer in both sexes in Warsaw population declined over the years 1963-1997. The 5-year relative survival rates, calculated for the period 1985-1989, were lower in men than in women (respectively 66 and 49%). This fact can be partly explained by more frequent occurrence of anaplastic tumours in men than in women (respectively 14.2 and 7.8%).

Neoplasms during the progression of pregnancy.

Restricting this review to dealing with pregnancy and its interaction with neoplasms limits us to the child-bearing years. Neoplasms may appear at all stages of species with true tissues and the incidence of malignancy in pregnancy is estimated to be 1:1,000. Almost 50% of these tumors are cervical cancers, followed by breast cancer, with an incidence of approximately 0.03%. The pregnant woman, in the same person, exhibits controlled growth (the pregnancy) and uncontrolled growth (the malignancy). In younger women, the neoplasms represent early stages of biological development and seem to arise practically from all maternal tissues. Geriatric changes in the neoplastic growth processes are missing. This article encompasses a review of the integration of neoplasms, the maternal body, the fetus and the placenta. The morphological and biochemical integration of the different processes is diversified. Mainly, we would like to address the interaction between pregnancy and common human malignancies like breast, cervix, and melanoma, but we will also review rare neoplastic complications. This way it is possible to treat the combined growth processes as they evolve from the initiated sperm, the ovum and continue via the placental development. These processes lead to the fetus and, in the pathological sense, to childhood complications, though most cases develop only portions of the process.

[Risk of malignant neoplasms among Polish population in 1986]. / Zagrozenie nowotworami zlosliwymi populacji polskiej w 1986 roku.

An analysis of the mortality for malignant tumors in Poland in 1986 is provided. The most frequent neoplasms noted in Poland were in 1986: in men cancer of the lungs (33.5% of all malignancies), cancer of the stomach (13.4%), prostate (4.8%), and pancreas (4.2%). In women the most frequent were: breast cancer (13.1%), cancer of the stomach (9.6%), lungs (7.8%), and cervix (6.7%). In 1986, significant difference in mortality rate was seen between men and women (prevalence of death in men) and between urban and rural areas (prevalence in urban areas). Moreover, persisting higher mortality rate for malignancies was noted in the western and central regions in comparison to eastern Poland. Mortality rate for malignancies in both men and women is higher in Poland than the average mortality rate in Europe.

[Clinical characteristics of patients with malignant neoplasms of the pancreas in case control studies in the Opole district]. / Kliniczna charakterystyka chorych na nowotwory zlosliwe trzustki w porównawczym badaniu przypadków w województwie opolskim.

Clinical data on 110 well-diagnosed cases of the pancreatic cancer collected in the study region between 1985 and 1987 by means of population case-control study are described. Out of 43.6% of the histologically diagnosed cases, 61.7% hand biopsy of the primary organ and 31.0% hand biopsy beyond the primary organ. There were 47.8% adenocarcinoma. Surgical findings (90% of the cases) included mainly isolated tumor of the head of pancreas (55.5%) or tumour of the head and other site of the organ (32.7%). 87.3% of the cancers was unifocal. Average diameter of tumour was 8 cm. Many metastases in gastrointestinal tract were found.

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for stomach cancer in Poland.

Urine samples were collected from 96 inhabitants of a high-risk rural area and a low-risk urban area for stomach cancer in Poland, according to the following protocol: (1) when they were undosed; (2) after ingestion of proline 3 times a day; and (3) after ingestion of proline together with vitamin C 3 times a day. The samples were analyzed for N-nitrosamino acids and nitrates, as indices of exposure to preformed and endogenously formed N-nitrosamines. The median values of N-nitrosoproline (NPRO) and N-nitrosothiazolidine 4-carboxylic acid (NTCA) excreted in the urine of undosed subjects were not different between the two areas; but N-nitrososarcosine and 3-(N-nitroso-N-methylamino)propionic acid levels were 3- to 4-fold higher in subjects of the high-risk area. After intake of proline, the NPRO level increased (p less than 0.02) only in subjects in the high-risk area; intake of vitamin C tended to inhibit this increase in NPRO and lowered the levels of other nitrosamino acids. The urinary level of nitrates was 1.4-fold, but significantly higher among subjects in the high-risk area than among those in the low-risk area; nitrate levels were not correlated with the amounts of cured meat or types of vegetables consumed. Urinary nitrate levels and excretion of NPRO, NTCA and the sum of all nitrosamino acids analyzed showed positive, though modest, correlations. These results indicate a higher potential for endogenous nitrosamine formation, possibly by intragastric nitrosation among subjects in the high-risk rural area.

Induction of natural killer cell activity in mice by injection of indomethacin.

The natural killer (NK) cell system of mice in the peritoneal cavity is of very low to undetectable activity, and testing peritoneal NK cells is a useful model to study the influence of activating substances upon local injection. Injection of indomethacin at doses of 100-400 micrograms/mouse caused a marked activation of NK cell activity which was maximal at 3 days and lasted for a total of 6 days. A similar albeit less marked effect was observed with other cyclooxygenase inhibitors such as aspirin. Prostaglandin E2 reversed the activation of NK cells induced by injection of indomethacin. The cellular count of the peritoneal population was 2-fold elevated after indomethacin injection but the percentage of macrophages in the washed-out cell population was decreased from 60% (controls) to around 20%. The NK cell nature of the effector cells activated by indomethacin was substantiated by the finding that previous injection of anti-asialo GM1 antibody prevented activation. Interferon could not be detected in the peritoneal wash fluid after injection of indomethacin, suggesting interferon-independent activation. However, the possibility of small interferon quantities being locally produced could not be excluded. In further experiments we found after intraperitoneal injection of indomethacin not only cells that killed YAC-1 targets in a 4-hour assay but also killer cells that were insensitive to anti-asialo GM1 and killed P815 cells in an 18-hour assay. We assumed that these were macrophages and have done further experiments with in vitro grown bone-marrow-derived macrophages. These could be activated for killing of P815 targets by the addition of indomethacin, but (to a lesser degree) also for killing of YAC-1 lymphoma cells.

Injection of anti-thy-1.2 serum breaks genetic resistance of mice against herpes simplex virus.

Nude mice have been shown to be as resistant to intraperitoneal infection with herpes simplex virus type 1 (HSV) as their heterozygous littermates. Here we document that both activation of natural killer (NK) cells and interferon induction were normal in nu/nu mice after injection of HSV. Injection of silica caused increased mortality by HSV in C57BL/6 mice. Silica, in addition, led to a significant reduction of NK cell activity but had no effect on the interferon response. Treatment of C57BL/6 mice with anti-asialo GM1 (an antiserum with a predominant effect on NK cells) caused complete abolition of the NK cell response, but had no effect on interferon induction or virus-induced mortality. In further studies a monoclonal anti-thy-1.2 antibody was utilized which possessed high activity in vivo in depleting T cell responses in mice. Injection of anti-thy-1.2 decreased NK cell activation but was without effect on the interferon response. Unexpectedly, in view of the data in nu/nu mice, this antibody increased HSV-induced mortality in C57BL/6 mice. Similar data were obtained when anti-thy-1.2 was injected into nu/nu mice. Our results are compatible with the hypothesis that T cell precursors sensitive to anti-thy-1.2 present in homozygous nude mice play a role in resistance against HSV. Furthermore, the data in the euthymic mice may indicate a role of T cells in the primary resistance of mice against HSV.

Attempts to correlate interferon induction and activation of natural killer cells by Corynebacterium parvum.

Intraperitoneal (i.p.) injection of Poly I:Poly C resulted in high interferon titers in the peritoneal wash fluid and in the serum of mice, which was maximal at 4 to 6 h after injection. In contrast, no interferon could be measured in the peritoneal fluid at various times after injection of C. parvum. Also, all attempts to induce serum interferon by C. parvum were unsuccessful. However, both Poly I:Poly C and C. parvum were causing the activation of Natural Killer (NK) cells in the cell population recovered from the peritoneal cavity. From adoptive transfer experiments, there was no indication that C. parvum induced a soluble mediator causing the activation of NK cells. There was also no indication that the interferon activity in the peritoneal cavity of C. parvum-treated mice might have been masked by the presence of an inhibitory molecule interfering with the antiviral effect of interferon in the assay. Our data may suggest activation of NK cells by C. parvum to be independent of interferon induction. Accordingly, we have observed that the injection of anti-interferon did not abolish NK cell activation by C. parvum. Thus, there is the interesting possibility of an interferon-independent mechanism of NK cell activation. However, we have additionally shown that doses of murine alpha/beta interferon as low as 1 IU per mouse caused a significant activation of NK cells in the peritoneal cavity upon i.p. injection. Thus, interferon itself is extremely potent in activating NK cells.

Role of interferon in the resistance of C3H/HeJ mice to infection with herpes simplex virus.

C3H/HeJ mice known to be defective in their responses to bacterial lipopolysaccharides, are more resistant to infection with herpes simplex virus (HSV) than the closely related strain C3HeB/FeJ. The increased resistance is reflected in higher early local interferon titers after HSV infection. However, NK cell activation by HSV is not correlated with resistance, since the NK cell response of C3H/HeJ mice was significantly lower than that of the control strain.

Herpes simplex virus - induced interferon production and activation of natural killer cells in SM/J mice. Relation to antiviral resistance.

We have studied the susceptibility of SM/J mice to intraperitoneal (i.p.) infection with herpes simplex virus type 1 (HSV) and have searched for correlations of susceptibility with the activation of Natural Killer (NK) cells and with local induction of interferon. SM/J were exceedingly susceptible to virus infection as they could be killed by less than 10 plaque forming units (PFU). The NK cell system of these mice, as measured by the activity of spleen cells against YAC-1 lymphoma cells, was hyperreactive, which is in agreement with previous findings of others. The peritoneal exudate cells (PEC) of uninfected mice had no activity. However, 18 h after i.p. injection of HSV NK cell activity was detected in the PEC population, which was at least as high as that in C57BL/6 mice that are resistant to HSV infection. Thus it appears as if the NK cell system does not play a major role in antiviral resistance in our experimental system. In contrast, from our previous work it would rather appear that the magnitude of the early local interferon response is important for resistance. The current data obtained in SM/J mice are in accordance with this, in that these highly susceptible mice are deficient in their early interferon response. Homozygous beige mice were found to be as resistant to infection with HSV as C57BL/6 mice. While the NK cell activity in their PEC population after injection of HSV was low, the titers of locally induced interferon were as high as those in the controls.

Diagnostic specificity of autoantibodies. II. Clustering of autoantibodies--role in diagnosis and in comparison to E--and EAC-RFC peripheral blood profiles and immunoglobulin levels.

Clustering of ANA and SMA was evaluated in patients with various internal diseases as a pattern of autoantibody formation. SMA was found in ANA positive patients with chronic hepatitis, undefined collagenoses and autoallergic thyroid diseases significantly more frequently, than in patients without any autoallergic disorders. The incidence of SMA in ANA positive cases with SLE and RA did not exceed their predictable by chance incidence. It was not found that clustering of autoantibodies is correlated with the E and C lymphocyte receptor abnormality as compared to the control group. The lowest count of E-RFC was found in SLE cases which differed significantly in this respect from the control group and also from chronic vasculitis cases. The clustering of autoantibodies is not correlated with hyperimmunoglobulinemia.

Cellular immunity in asbestosis.

A highly statistically significant correlation was found between asbestosis and impaired responsiveness in skin reaction to intermediate and second strength tuberculin and SK-SD. Considering ANA incidence these antibodies were found with higher frequency in asbestos workers who lacked a cutaneous response to the recall antigens. In asbestosis cases peripheral blood lymphocyte profiles are also abnormal demonstrating low proportions of E-RFC. Moreover, MIF test results showed the impairment of this cytokine generation when lymphocytes were stimulated with SK-SD, PPD and PHA in asbestosis cases. The lymphocyte transformation study documents an impaired response mainly to a lower dose of PHA and ConA in asbestosis cases and in asbestos workers with ANA.