[Effect of smoking on pulmonary glycoprotein metabolism and phospholipid content]. / Einfluss des Rauchens auf den pulmonalen Glykoprotein-Stoffwechsel und Phospholipid-Gehalt.

We investigated the influence of smoking on the cell count, proteins and phospholipids in the bronchoalveolar lavage fluid in 371 patients. In the case of smokers, the cell count and the content of N-acetylglucosaminidase-an enzyme involved in glycoprotein metabolism were elevated. In contrast, the concentrations of protein, alpha amylase and phospholipids were lower than in the nonsmokers. The figures for ex-smokers were, for the most part, similar to those of the non-smokers.

Pharmacodynamic mechanism and therapeutic activity of ambroxol in animal experiments.

The mucokinetic activity of ambroxol was demonstrated as an increase in mucus or particle transport rate on the frog palate and in guinea pig tracheas. To clarify the mechanism we examined the influence of the drug on the ciliary beat frequency (CBF) of isolated cells from guinea pig tracheas. Ambroxol significantly stimulated the CBF up to 10.8%, salbutamol up to 19.5%. The effect of ambroxol on CBF certainly contributes to, but does not explain the more pronounced increase in transport rate. Thus a stimulation of the mucociliary transport rate by the other major pharmacodynamic mechanisms, secretagogue activity and stimulation of pulmonary surfactant, has to be considered. The therapeutic activity of ambroxol in models of the infant and adult respiratory distress syndrome and of the chronic bronchitic syndrome is reviewed.

Aganglionosis of the colon. Morphologic investigations in 524 patients.

2014 biopsies and surgical specimens of 524 patients with suspected aganglionosis of the colon were analyzed using enzyme histochemical techniques for acetylcholinesterase and lactate dehydrogenase. The diagnosis could be confirmed in 70 patients. Hypoganglionosis was found in 6, neuronal dysplasia (or hyperganglionosis) in 2, and a complete lack of intramural neurons and nerve fibers in 1 patient. The disease was found to occur most often during the first year of life (65.7%) and to be more common in males than females (3.3:1). Enzyme histochemistry is useful for the final diagnosis of aganglionosis provided the biopsy contains mucosa and parts of the submucosa of the colon.

Successful transplantation of a human leukemia cell line into nude mice: conditions optimizing graft acceptance.

Conditions were determined for successful subcutaneous tumor development of MOLT-4 human T-cell leukemia cells in BALB/c nude (nu/nu) female mice. MOLT-4 cells injected alone at one site resulted in tumors in none of 21 mice, whereas MOLT-4 cells injected with X-irradiated human fibrosarcoma cells (HT-1080) at another site resulted in tumors in 5 of 21 mice. When X-irradiated three times with 200 rad over a 3-week period and then inoculated with MOLT-4 cells and X-irradiated HT-1080 cells, 19 of 25 mice developed tumors, which indicated that a combination of X-irradiation of the recipients and inoculation of an admixture of the leukemia cells with X-irradiated fibrosarcoma cells markedly increases tumor incidence. The cells growing in the tumors had the characteristics of MOLT-4, as assessed by marker studies and histology.

Regulation of immune responses against the syngeneic ADJ-PC-5 plasmacytoma in BALB/c mice. I. Analysis of immune parameters involved.

The non-secreting variant of ADJ-PC-5 plasma cell tumour of BALB/c mice is a highly malignant tumor, the LD50 being 3 x 10(1) cells/mouse after intraperitoneal injection. Nevertheless, immunization against the tumour is possible. Four injections of 10(7) X-irradiated tumour cells at weekly intervals render up to 95% of mice resistant to an otherwise lethal challenge with 10(3) living tumour cells. The immune responses are both T cell-mediated cellular cytotoxicity and antibody-mediated cytotoxicity as assessed by in vitro tests. Immunity can also be transferred in vivo into recipient mice by either spleen cells or immune sera. Specificity of both types of immune responses was determined. The results indicate that the cell-mediated and the humoral immune response are directed against cell-surface antigens associated with endogenous murine leukemia virus.

Regulation of immune responses against the syngeneic ADJ-PC-5 plasmacytoma in BALB/c mice. II. Suppression of T-cell cytotoxicity by pretreatment of mice with subimmunogenic doses of tumour cells.

Protective immunity towards a lethal dose of 10(4) living ADJ-PC-5 cells can be induced in 56% of BALB/c mice by treating them with 10(7) irradiated cells. This protection can be modulated by pretreatment of animals with lower numbers of irradiated tumour cells. Repeated injections of 10(1) cells before immunization and challenge with tumour cells lead to tumours in only 16% of the animals, whereas repeated injections of 10(5) cells shift the tumour incidence to 78%. The enhanced tumour incidence is paralleled by suppression of T-cell cytotoxicity which can be transferred by spleen cells into 100 r-irradiated BALB/c mice. The possible significance of induction of specific immunosuppression during the initial stages of tumour growth is discussed. It is stressed that this suppression becomes effective at a dose 10(3) times lower than that which could induce protective immunity.

Deficiency of natural killer cell activity in patients with chronic lymphocytic leukemia.

Natural killer (NK)6 cell activity of peripheral blood lymphocytes against human leukemia cell lines was measured in patients with chronic B-cell lymphocytic leukemia (CLL) and age- and sex-matched controls. In order to remove the leukemia cells that interfere with the in vitro assay we (1) isolated lymphocytes that form rosettes with sheep red blood cells (SRBC) or (2) lysed the CLL cells with a monoclonal anti-B cell antibody and complement. NK activity in either lymphocyte preparation from nine of 10 patients with advanced disease was not detectable and, when calculated in terms of lytic units per ml of blood, as at least seven times lower than in controls; only one of these patients exhibited activity within the control range. Two patients with early disease had measurable, but low, NK-cell activity. Prolongation of the NK cell assay from 6 to 18h gave rise to significant killing in the CLL patients lacking NK cell activity in the 6-h assay; however, the activity still was six times lower than in controls. Treatment of leukemia cell-depleted lymphocytes from CLL patients with human fibroblast interferon or the interfeon inducer poly 1:C enhanced NK-cell activity in the two early stage patients but this treatment was ineffective in three later stage patients. The percentage of cells with characteristics of NK cells, i.e. those with receptors for SRBC and Fc-portion of IgG, was four times higher in CLL patients and the percentage of lymphocytes binding to NK-sensitive target cells was equal to that in controls despite the fact that, in the majority of patients, lysis of the target cells by the lymphocytes does not ensue. The NK deficiency may be responsible for the increased incidence of secondary malignancies in CLL patients.

[Early judgement on the results in radiation therapy of colorectal cancer: determination of carcinoembryonic antigen (CEA) in blood serum at daily intervals from the beginning of irradiation (author's transl)]. / Frühzeitige Erfolgsbeurteilung der Strahlentherapie von rektosigmoidalen Karzinomen. Die Bestimmung des Karzinoembryonalen Antigens (CEA) im Serum in Tagesabständen zu Beginn der Bestrahlung.

Carcinoembryonic antigen (CEA) and lactatedehydrogenase (LDH) as tumor cell markers have been determined in the blood serum of 10 patients with colorectal cancer, who underwent preoperative irradiation with 200 to 250 rad daily (total focal dose 2000 to 2500 rad). Daily analysis was made during the irradiation, and, moreover, a determination 2 weeks after the resection of the tumor. Simultaneously CEA and LDH were determined in 10 controls. Serum CEA and LDH levels were found significantly increased in tumor patients as compared to controls. The course was characterized by a peak of LDH on days 4 and 7 from the onset of radiation treatment, while serum CEA did not show a peak in the total of the tumor patients; but in 3 individual patients a peak was detected. In 5 patients, with low CEA values from the beginning, no significant modifications of CEA did appear. Thus, some of the patients undergoing irradiation revealed CEA kinetics conform to theoretical considerations, suggesting a response to irradiation of the colorectal carcinoma. The prognostic value of the early CEA kinetics during radiation treatment should be examined in patients being irradiated for inoperable local recurrence.

High-performance liquid chromatographic analysis of methadone hydrochloride oral solution.

A direct and rapid high-performance liquid chromatographic assay for methadone hydrochloride in a flavored oral solution dosage form is described. A syrup sample, one part diluted with three parts of water, is introduced onto a column packed with octadecylsilane bonded on 10 micrometer porous silica gel (reversed phase). A formic acid-ammonium formate-buffered mobile phase is linear programmed with acetonitrile. The absorbance is monitored continuously at 280 or 254 nm, using a flow-through, UV, double-beam photometer. An aqueous methadone hydrochloride solution is used for external standardization. The relative standard deviation was not more than 1.0%. Drug recovery from a syrup base was better than 99.8%.

Simultaneous assay for six alkaloids in opium, using high-performance liquid chromatography.

A method is described for the quantitative determination of morphine, codeine, cryptopine, thebaine, papaverine, and narcotine in opium by high-performance liquid chromatography. The alkaloids are isolated from a dilute acid extract by adsorption on an Amberlite XAD-2 resin column and eluted first with methanol and then with chloroform-methanol (3+1). After solvent removal by reduced pressure evaporation, the alkaloids are redissolved in chloroform-methanol (3+1). The sample solution, plus brucine as an internal standard, is injected onto a Corasil II column and eluted with hexane that is gradient programmed with a solution of chloroform-methanol-diethylamine (100+300+1). The absorbances of the separated alkaloids are continuously monitored at 254 nm, using a flow-through ultraviolet double-beam photometer.

Automated method for determining calcium disodium edetate in iodinated contrast media parenterals.

An automated method, based on the chelating reaction of calcium disodium edetate with zirconium and the subsequent determination of excess zirconium reacted with xylenol orange, was developed. The procedure is applicable to parenterals consisting of iodinated contrast media. Familiar modules of an automated analyzer were used, but the method can be performed manually if the sample load does not warrant automation. The pH should be controlled between 0.3 and 0.5. No interferences were encountered. Twenty samples per hour can be run on prepared sample solutions. The precision of a single determination, at the 95% confidence level was plus or minus 0.008 mg/ml with a limit of detection near 0.40 mg/ml.