The role of surgical resection and the effects of neo-adjuvant therapy in the management of small cell lung cancer.

A study was conducted on 58 patients who underwent surgery for small cell lung cancer (SCLC) as resection or exploratory thoracotomy, and 43 patients encountered during the same period who received no surgical treatment. The following conclusions were drawn from our analysis: At stage I, an operation is desirable, regardless of the subtype of SCLC, but chemotherapy should be given first; at stages II and III, by the addition of surgery after neo-adjuvant chemotherapy, "state-of-the-art" results for limited SCLC can be surpassed; in patients with stage II disease on whom curative resection has been performed, particular attention must be paid to the possibility of metastasis to the brain; and finally, exploratory thoracotomy did not bring about the early death of patients or reduce the quality of life, but only delayed chemotherapy for about one week, while enabling the staging and histological subtype of SCLC to be clarified.

Use of night soil in agriculture and fish farming.

The use of untreated night soil as a fertilizer in agriculture or as a source of nutrients in fish farming presents a considerable health hazard in the form of pathogens and parasites. A pilot study is reported in which night soil was placed in an anaerobic digester, producing biogas and residual organic matter. The latter was introduced into biostabilization ponds, and nutrients were thus obtained for the rearing of fish. Fish ponds receiving nutrients derived from treated night soil were less contaminated than ones to which untreated night soil was applied, and the fish reared in them were of superior quality.

Increase in protein kinase C activity is associated with human fibroblast growth inhibition.

Protein kinase C (PKC) activity and DNA synthesis were measured in human fetal bone marrow fibroblasts following treatment with tumor necrosis factor alpha (TNF alpha) (500 U/ml) or conditioned media containing natural cell proliferation inhibitor (CM-NCPI). Treatment with TNF alpha led to growth stimulation (120 +/- 7% of control in 24 h, 141 +/- 6% in 72 h). At the same time particulate PKC activity diminished, reaching 55 +/- 8% of control in 24 h and remaining at this level at 72 h. CM-NCPI treatment of the cells resulted in a decrease in DNA synthesis (by 39 +/- 6% in 2 h, by 58 +/- 5% in 24 h, and by 78 +/- 8% in 72 h). This was accompanied by a significant rise in particulate PKC activity which increased over 3-fold in 2 h, over 5-fold in 24 h, and up to 11-fold in 72 h. This 11-fold elevation was maintained after 2 week exposure of the fibroblasts to CM-NCPI. The PKC inhibitor neomycin abolished CM-NCPI induced growth inhibition, whereas PKC activator 12-O-tetradecanoylphorbol 13-acetate intensified it. These results suggest that CM-NCPI acts as PKC activator and that negative growth regulation by extracellular agents may involve stimulation of PKC activity.

[DNA analysis of resected pulmonary adenocarcinoma].

The nuclear DNA content was determined by flow cytometry (FCM) in 155 resected specimens (122 paraffin-embedded and 33 fresh frozen specimens) of primary adenocarcinoma of the lung obtained at our department during the 8 years from 1982 to July, 1990. Aneuploid patterns were observed in 106 specimens (68.4%), and the diploid patterns in 49 (31.6%). No difference was observed in the age, sex, or clinical stage between the two groups. As for the relationship of the presence or absence of vascular infiltration with the DNA index (DI) and the heterogeneity index score (HIS), the percent positivity of vascular infiltration was 38.1% in the group with 1 less than or equal to DI less than 1.5 but nearly twice higher at 63.6% in the group with 1.5 less than or equal to DI. The percent positivity of vascular infiltration was 29.4% in the group with HIS less than 100 but 62.5% in the group with 100 less than or equal to HIS. Concerning the relationship between the ploidy pattern and outcome, the 5-year survival rate was 28.0% in the aneuploidy group and 65.1% in the diploid group, the outcome being significantly poorer in the first group. Concerning the relationship between DI and outcome, the 5-year survival rate was 14.9% in the group with 1.5 less than or equal to DI as compared with 55.4% in the group with 1.0 less than or equal to DI less than 1.5. DNA analysis was made also in bronchoscopic brushing specimens to examine the possibility of preoperative evaluation of the prognosis of lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

Phorbol ester-treated human acute myeloid leukemia cells secrete G-CSF, GM-CSF and erythroid differentiation factor into serum-free media in primary culture.

Upon treatment with the phorbol ester, tetradecanoylphorbol 13-acetate (PMA), peripheral mononuclear blood cells from patients with acute myeloid leukemia secrete into serum-free cell-conditioned media (PMA-CCM) at least three distinct nondialysable 'hematopoietic' factors: granulocyte-colony-stimulating factor (G-CSF), granulocyte/macrophage-colony-stimulating factor (GM-CSF) and erythroid differentiation factor (EDF, activin A). G-CSF was identified by its stimulation of [3H]thymidine incorporation into a G-CSF-responsive cell line, NSF-60, and the inhibition of its stimulation by a G-CSF-specific monoclonal antibody (MAB). GM-CSF was identified by its stimulation of [3H]thymidine incorporation into a GM-CSF-responsive line, TALL-101, and the inhibition of its stimulation by a GM-CSF-specific MAB. EDF was identified by its ability to stimulate erythroid differentiation in mouse erythroleukemia cell lines, its identical retention times to those of authentic EDF on three successive reverse-phase HPLC columns and characterization of its penultimate N-terminal residue as leucine which is the same as that of authentic EDF. Both authentic EDF and the erythroid-stimulating activity in PMA-CCM were found to act synergistically with a suboptimal inducing concentration of a well-studied inducing agent, dimethyl sulfoxide, in inducing erythroid differentiation. In addition, a fourth activity was observed in PMA-CCM: normal human fetal bone marrow cell-proliferation stimulating activity (FBMC-PSA). FBMC-PSA was identified by its ability to stimulate the growth of granulocytes and macrophages in FBMC suspension cultures, which neither recombinant G-CSF or GM-CSF were found to do.

Effect of addition oral contraceptives in chicks diet.

Contraceptives are used in poultry production aiming to increase the profit. The present study resulting in some data revealed that the application of contraceptive pills in chicks diet is negatively affecting the chick performance as shown from the insignificant (P greater than or equal to 0.05) decrease of body gain, feed conversion efficiency, deposit fat percent, liver weight percent and blood glucose content. Dressing percentage and total edible parts percentages, did not differ significantly (P greater than 0.05). Biochemical parameters in blood were measured and the results are discussed.

Fibroblast growth inhibitor.

A new cytokine has been recognized in the conditioned media (CM) of freshly isolated acute myelocytic leukemia cells, cultured with 12-0-tetradecanayl phorbol acetate (TPA) 10(-8)M. The fraction with 70,000 MW was separated from CM by ammonium sulfate precipitation, ion-exchange cation and anion chromatography, and Sephadex G-200 gel filtration. It was a fibroblast growth inhibitor (FGI). This substance stopped fetal and skin (MALME 3 line) fibroblast propagation. The cytostatic effect was reversible on removal of FGI. At the same time, FGI did not inhibit macrophage proliferation. The fraction stimulated formation of monocytic and granulocytic colonies altered the phenotype of human U-2 osteosarcoma cells grown from epithelial-like to fibroblast-like cells, and stimulated differentiation of leukemic cells along the macrophage path. Some cells of promyelocytic leukemia line HL-60, grown in the presence of FGI, were stimulated to differentiate and some underwent lysis. The response to FGI of cells from different patients varied.

Mononuclear macrophage (M-CFC) colony formation in semisolid media in the absence of exogenous GM-CSF.

Human fetal bone marrow (FBM) cells were examined for the ability to form colonies in the absence of exogenous colony-stimulating factor (CSF) in double layer agar, methylcellulose (MC), and in agar-MC (agar underlayer, MC overlayer) culture systems. Without exogenous CSF, macrophage colonies (M-CFC) were formed in a combined culture of agar and MC. Aggregates of 5-40 cells were observed on day 7. Gradually, large compact colonies which survived for 10-12 weeks of cultivation, were formed. They were composed of mononuclear monocytes and multinucleated cells. M-CFC progenitors were nonadherent, but their progeny became adherent during differentiation within the colony. Colony formation was cell-dose-dependent. Depletion of monocytes increased the number of colonies in agar-MC cultures and stimulated the development of some macrophage colonies in MC. Survival of monocyte progenitors was not dependent on CSF. Neither was their proliferation nor partial differentiation in agar-MC cultures. CSF increased M-CFC colony efficiency, however, if it was present when cultures were initiated. Addition of CSF to M-CFC growing for 2-5 weeks in CSF-deprived medium stimulated monocytes proliferation and transformation into macrophages. Epithelioid cells, an increase in the number of giant multinucleated cells, and granulocyte multiplication were also observed. The absolute dependence of macrophage colony formation on CSF described by others might be a result of inadequate culture conditions due to agar rather than an intrinsic physiological requirement.

Multiplication of human fetal myelomonocytic precursors in medium conditioned by acute myelocytic leukemia cells treated by 12-O-tetradecanoyl phorbol 13-acetate (TPA).

An 8-21 fold multiplication of myeloid cells and macrophages was observed in tissue culture from human fetal bone marrow. Proliferation of the cells was triggered by medium conditioned by acute myelocytic leukemic cells exposed to 12-O-tetradecanoyl phorbol 13-acetate (TPA). The medium was designated as TPA-treated cell conditioned medium (TPACCM). The cycle of events in fetal bone marrow cell culture began with a sharp decrease in the total number of cells. At this juncture a predominance of primitive macrophage-like cells positive for macrophage markers was present in the culture. The process of multiplication began with rapid proliferation of promyelocytes. Simultaneous proliferation of granulocyte-macrophage (GM) colony forming cells (CFC) indicated that at least some of the promyelocytes might act like CFC. The absolute number of committed CFC then increased 5-11 fold, the number that approximated a total multiplication of FBM cells. The proliferation continued with the culture containing some blast cells and showing simultaneous differentiation of the cells into mature granulocytes and macrophages. The cells with macrophage markers persisted throughout the culture period. To determine more precise definition of the role of primitive macrophages and promyelocytes in FBM cell multiplication, experiments with purified fractions of these cells have to be done. TPACCM purification and isolation of active substances is also suggested. These investigations might result in obtaining a pool of BM cells in vitro suitable for BM transplantation.

Isolation of prolactin-producing cells from first and second trimester decidua.

Two cell types isolated and purified to homogeneity from human decidua obtained at 8-17 weeks of gestation were shown immunocytochemically to correspond to decidual and epithelial cells in the tissue of origin. The decidual cells reacted with antihuman PRL antiserum, and epithelial cells reacted with antiserum against keratin, an epithelial cell marker. Decidual and epithelial cells were cultured separately to determine their abilities to release PRL to the medium. Decidual cells released 140-410 ng PRL/mg protein in 24 h, whereas no PRL was detectable in cultures of isolated epithelial cells. These homogeneous preparations provide an excellent system with which to study the regulation of PRL production and other biochemical properties of decidual components.

Cervical priming prior to dilatation and evacuation: a comparison of methods.

Vaginal administration of prostaglandin analogues resulted in cervical changes that facilitated dilatation and evacuation in 80 patients in the late first trimester and the second trimester of pregnancy. When 0.5 mg and 1.0 mg of 15(S)-15-methyl-prostaglandin F2 alpha (15-ME-PGF2 alpha) was compared to 30 and 60 mg of 9-deoxo-16,16-dimethyl-9 methylene prostaglandin E2 (PGE2 analogue), the PGE2 analogue appeared to have more cervical ripening effect than did the 15-ME-PGF2 alpha. Overall, the 30 mg PGE2 vaginal suppository seemed to offer the most optimal combination of effectiveness, sufficient cervical dilatation, and minimal side effects. With the prostaglandins, maximal cervical effect was observed at 4 to 5 hours; this rapid effectiveness allows administration of the prostaglandin to accommodate a 1-day stay for surgical evacuation. The preoperative cervical priming results with the prostaglandins were compared to those obtained with the use of laminaria tents. Although the number of patients who needed further dilatation at the time of operation was less with the laminaria, the incidence of complications and the time for adequate dilatation were higher in that group.

A new abortion technique: intravaginal and intramuscular prostaglandin.

The 15-methyl analog of prostaglandin F2 alpha (15-ME-PGF2 alpha), administered in a 3-mg dose via a single vaginal suppository and supplemented at 24 hours by intramuscular injection(s) of 250 micrograms, successfully induced abortion in 80 of 81 patients in the midtrimester of pregnancy. The mean abortion time was 19.6 hours. Two thirds of the patients aborted after treatment with the suppository alone in a mean time of 14.6 hours; the remaining 27 patients required intramuscular injections of 15-ME-PGF2 alpha to effect expulsion of the products of conception. Twenty-six of these 27 patients subsequently aborted in a mean total abortion time of 29.6 hours. Fifty-eight patients aborted within 24 hours of the initial prostaglandin administration, and 78 aborted by 36 hours. Parity and length of gestation did not significantly affect abortion time in this series, although the mean abortion time for parous patients and patients with gestations earlier than 17 weeks tended to be somewhat shorter than that of nulliparous patients and those with more advanced gestations. The placenta was spontaneously expelled in the majority of patients. Abortion was incomplete in 3 patients and required curettage. Uterine activity, as measured via an intraamniotic catheter in 6 patients, developed very gradually with the suppository, peaking at 3 hours after insertion, and was characterized by regular contractions with low intrauterine baseline tonus. The gastrointestinal side effects that occurred in 59% of patients who received the suppository were also most frequently observed at 3 hours after administration. In contrast the gastrointestinal disturbances elicited by intramuscular injections of the analog immediately followed the administration.

Pulmonary and hepatic activities of membrane-bound enzymes in man and rat.

The lung of adult man contains several times more 5'-nucleotidase (EC 3.1.3.5), alkaline phosphatase (EC 3.1.3.1) and gamma-glutamyl-transpeptidase (EC 2.3.2.2) per gram than does that of the 12- to 16-week fetus. In rat lung, too, there is a drastic developmental rise in these activities. Opposite changes in two of the enzymes occur during hepatic differentiation: alkaline phosphatase decreases in the rat, and gamma-glutamyl-transpeptidase is ten times higher in the fetal than in the adult liver of both species.