Search

Objective : Assessment of the appearance, distribution and numerical density of immune cell populations in the normal human uterine cervix. Study design : Setting : University Hospital Gasthuisberg. Subjects : 29 healthy women undergoing total hysterectomy for non-cervical benign uterine disease. Analysis : Immunohistochemistry and morphometrical analysis on histological sections containing ectocervix, transformation zone and endocervix, using antibodies against the following antigens: HLA-DR, CD4, CD22, CD1a and CD8. Statistical analysis : Wilcoxon rank sum test. Results : Lymphocytes in the epithelial and stromal compartments are predominantly T-lymphocytes. Intraepithelial T-lymphocyte and Langerhans' cell densities and their distribution are not influenced by the menstrual cycle and are the same in both ectocervix and transformation zone. Conclusion : The wide variation of T lymphocyte subpopulations and Langerhans' cell densities in the normal epithelium of the uterine cervix is stressed. We are the first to present a large and well-defined control series, which is indispensable to study the effect of smoking and other factors on the cervical immune system.

Previous reports have supported an association between tobacco smoking and cervical neoplasia. Our observations show an association between smoking and a reduction of the numerical densities of Langerhans cells and of helper/inducer T lymphocytes in the squamous epithelia of the transformation zone of the uterine cervix. This suggests a local impairment of cell-mediated immunity by smoking. This immunosuppressive effect could support the concept that smoking is an independent risk factor for cervical neoplasia.

Cotinine levels in blood and cervical fluid of smokers and non-smokers were analysed using capillary-column gas chromatography. These levels were not related to numerical cell densities of intraepithelial S100-protein- and LN2-positive Langerhans cells or to MAC-387-positive macrophages in the stroma of the transformation zone of normal uterine cervices. A decrease in the number of Langerhans cells was noted in smokers, especially in those using oral contraceptives (OCs). Macrophages were more numerous in the endocervical stroma of smokers, suggesting a local response to smoke constituents. These findings may indicate a synergistic suppression of local cervical immunity by smoking and OCs.

This study evaluates the presence of Langerhans' cells and expression of L1 antigen in squamous epithelium of the normal and dysplastic transformation zone of the cervix uteri and determines the influence of tobacco smoking and pregnancy. Women who smoked and pregnant women showed a decrease of Langerhans' cell counts in normal epithelium. In cervical intraepithelial neoplasia (CIN) 1 lesions, decreased Langerhans' cell counts were noted. L1 antigen expression was significantly less in CIN of all grades. Normal squamous epithelium of smokers showed weaker staining for L1 antigen but total staining scores were not significantly different. These data suggest a decrease in epithelial cell-mediated immune response in smokers, pregnant women and in low-grade CIN. Dysplastic squamous cells probably have intracellular regulatory problems independent of other immune cells.

Three sequential oestradiol valerate (E2V) and cyproterone acetate (CPA) combinations based on 11 days of oestrogen and 10 days of oestrogen-progestogen administration were investigated during hormone replacement therapy in two prospective, double-blind randomized trials. Treatment A comprised 2 mg E2V and 1 mg CPA, treatment B, 1 mg and 0.5 mg and treatment C, 2 mg and 2 mg, respectively. During treatment A hot flushes (P0.0001), night sweating (P0.0001), depression (P = 0.0001), dizziness (P = 0.0001) and insomnia (P = 0.003) decreased significantly. The only side effect was breast tenderness, which was experienced by 18% of the women. Weight and blood pressure, thyroid, adrenal, liver and kidney functions, parathyroid hormone and vitamin D, platelets and blood cell counts did not change during the 12 months of therapy. In the women who received treatment A the menstrual flow became less abundant during the early months of treatment (P0.0001), the menses being scanty in around 30% of the women, while some 10% had amenorrhoea. Spotting occurred in 10-20% of the subjects. Endometrial biopsies were atrophic in 10% of the women, whereas a normal secretory phase was observed in 45% and irregular secretion in 45%. After careful analysis using visual analog scales, these findings were interpreted as indicating a high-normal progestational effect. In comparison with the pattern observed in normal menstrual cycles the women who received treatment A had a more heterogenic glandular epithelium, with more papillae, larger stromal cells, a more pronounced decidual reaction and more fibrinoid material. No cases of hyperplasia were seen. Treatment B was less effective than treatment A in relieving climacteric complaints. Irregular bleeding was troublesome in over 20% of cases and amenorrhoea occurred in 50%. Endometrial biopsies were atrophic in 57% of the women. The effectiveness of treatment C in alleviating flushes, sweating, dizziness and depression was the same as that of treatment A. The decrease in menstrual flow during the early months and the incidence of amenorrhoea (approx. 10%) and atrophic endometria (approx. 10%) were comparable. Detailed analysis revealed that C had an even stronger progestational effect than A. It was concluded that A was the treatment of choice in comparison with B and C. It proved highly effective in treating climacteric complaints, had no side effects apart from breast tenderness, provided good cycle control and induced a physiological secretory transformation of the endometrium.(ABSTRACT TRUNCATED AT 400 WORDS)

Mammary carcinoma tissue from 514 primary breast cancer patients were all biochemically and histochemically analyzed for both estrogen receptors and progesterone receptors. The dextran-coated charcoal (DCC) method measured the ER and PR as defined by Scatchard analysis, ligand competition experiments and target organ specificity. The ligands, estradiol-6-carboxymethyloxime-BSA-fluoresceine isothiocyanate and hydroxyprogesteronehemisuccinate-BSA-tetramethylrhodamine isothiocyanate, used for histochemistry, did not bind to either ER or PR and were mainly bound to the membrane fraction of isolated breast cancer cells. Fluorescence was not specifically inhibited by estrogens or progestogens. In addition, "estrogenic" always coincided with "progestogenic" fluorescence. The binding of the fluoresceine compounds to tissue slides depended on the large steroid hormone substitution on the bovine serum albumin molecule. Clinical parameters, known to be related to ER and PR did not correlate with the histochemical results. The observations indicated the impossibility of specific steroid receptor detection by the histochemical method. Therefore, up to the present, evaluation of hormone dependency and prognosis in human breast cancer cannot be based on this approach.

Summary Ultrastructurally atypical bronchial cilia are studied and semiquantitatively analysed in 24 children suffering from recurrent respiratory tract infections with or without bronchiectasis. In patients with Kartagener's syndrome normal-looking and shortened dynein arms are present at some axonemal microtubular doublets. This finding suggests that the polymerization or assemblage of dynein molecules on microtubules only is defective but not totally lacking. Bilateral, local and partial absence of dynein arms is demonstrated in some of the patients with acquired unilateral bronchiectases. These patients also reveal anomalies of the “9 + 2” microtubular axonemal pattern. It is suggested that these abnormalities of the tubulin-dynein system are local and acquired defects that may impair bronchial mucociliary clearance. None of the patients with pneumonia and asthma or with cystic fibrosis studied show any anomalies of the dynein arms. However aberrant axonemal microtubular patterns and other ciliopathies such as naked axonemes and megacilia are present at times in these patients. We postulate that these atypical cilia are secondary acquired abnormalities. Only some patients with bacterial or viral pneumonia demonstrate a partial lack of dynein arms in bronchial cilia. Other ciliopathies such as megacilia, naked and intracytoplasmic axonemes and apical blebs are more frequent and more common in these patients. We suppose they manifest a secondary and rather aspecific pathogenic influence upon the bronchial ciliary substructure.

Electron microscopic studies revealing a lack of the dynein arms of the microtubular doublets of bronchial cilia and sperm tails suggest that Kartagener syndrome is a special manifestation of a hereditary disease, now referred to as the immotile cilia syndrome (Eliasson et al. N Engl J Med 297: 1, 1977). Anomalies of the bronchial cilia were observed in 5 patients with recurrent pulmonary infections. Patient 1 had Kartagener syndrome and an absence of the outer dynein arms in most ciliae, although occasional shortened and even normal arms were seen. Patient 2 and 3 had unilateral bronchiectases without family history of Kartagener syndrome. Serial studies of the bronchial epithelium showed a bilateral lack of the inner dynein arms and incomplete outer arms. These abnormalities persisted after recovery from acute pulmonary infection. In patients 4 and 5 with recurrent pulmonary infections without bronchiectases, many shortened outer dynein arms were observed, but these anomalies disappeared after recovery. In all 5 patients additional striking ciliary anomalies were found: megacilia, fused cilia, nude cilia and completely disorganized axonemes. These defects were more numerous in the patients without bronchiectases. Our observations suggest that anomalies of the bronchial ciliary microtubular system may not only be congenital but also acquired, and could be an important factor explaining some cases of repeated airway infection and bronchiectases.