[Routine microscopic examination and culture. Benefits and clinical consequences].
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Biomedical subjects
Publications and source records attributed to B Christensen.
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The effect of the skin tumor-promoter TPA (12-O-tetradecanoylphorbol-13-acetate) on expression of cellular proto-oncogenes has been examined in cell lines derived from human urothelium. A single treatment with TPA (1 microgram/ml) increased the transcription of c-fos and c-myc proto-oncogenes at least 20-fold in the mortal cell line HU 1752. The induction was transient and was accompanied by a rapid but transient change in cell morphology. When immortalized cell lines were treated with TPA a similar rapid and transient morphological response was observed, but the TPA treatment only increased the level of c-fos mRNA, suggesting that the normal regulation of c-myc transcription is altered in immortalized cells irrespective of their tumorigenic properties. The levels of c-Ha-ras and c-Ki-ras mRNAs were unaffected by TPA treatment in all cell lines.
The immortalized but non-tumourigenic and non-invasive human urothelial cell line, Hu 609, known to express the appropriate HLA A,B antigens (A2,-; B5,-) has previously been demonstrated to undergo "spontaneous" in vitro transformation into an invasive and tumourigenic subline, Hu 609T/MV. This subline does not express the polymorphic HLA epitopes. In the present investigation we have followed two additional "spontaneous" transformations of the Hu 609 cell line into malignant sublines. Evidence is presented that the development of morphological changes and tumourigenicity were accompanied by a gradual loss of the expression of polymorphic HLA A,B epitopes and a reduction in the expression of monomorphic HLA A,B,C antigens. Antigens could be detected again after neuraminidase treatment. We conclude that the urothelial Hu 609 cell line after "spontaneous" transformation still possesses the HLA A,B epitopes. The observed quantitative differences in HLA expression between Hu 609 and its malignant sublines may be due to masking of the HLA antigens by sialic acid containing tumour-associated highly branched glycoproteins.
A questionnaire was sent in 1984 to 97 children with urticaria, who had previously been seen in Danish general practice during a period of three months in 1982. The questionnaire included questions about provoking factors and the course of the disease. Replies were received from 79 children, 46 of whom had experienced one attack only, and 33 had had several attacks. Fifteen percent of the former and 48% of the latter suggested a variety of provoking agents, which were mainly food and food additives in the recurrent group. Previous infections were not suspected, though 20% had signs or symptoms of infection at the registration in 1982. It is suggested that a first episode of urticaria should be investigated by the practitioner only, with simple questioning and perhaps symptomatic treatment, because the first attack is often the sole one.
The validity of previous recommendation of early thoracoscopy and tetracycline pleurodesis in the management of spontaneous pneumothorax without thoracoscopically visualized true cyst was assessed under non-trial, normal hospital conditions. Among 46 patients treated during a year, seven underwent immediate thoracotomy following finding of large cysts. Of the remaining 39 patients, 11 had recurrence of pneumothorax after a median of 11 (range 2-64) weeks. Repeat thoracoscopy then showed large cyst or bullous emphysema in seven cases. Tetracycline pleurodesis was again performed in the others. In continued observation for at least 2 years there were no further recurrences. The importance of meticulous thoracoscopy is stressed. The demonstrated diagnostic errors do not detract from the value of tetracycline pleurodesis when spontaneous pneumothorax is caused by rupture of only tiny blebs on the surface of an otherwise healthy lung. The procedure is fast, simple and efficacious.
Unscheduled DNA synthesis (UDS) was studied by quantitative autoradiography in human urothelial cells of three transformation grades (TGr I-III). Cells incubated in arginine-free medium supplemented with hydroxyurea showed dose-dependent UDS after administration of agents injurious to DNA, while the scheduled synthesis of DNA was nearly totally suppressed. UDS was demonstrated after treatment with the ultimate carcinogen N-methyl-N-nitroso-N'-nitroguanidine (CAS: 70-25-7) or with the procarcinogen 4-nitroquinoline-1-oxide (4-NQO; CAS: 56-57-5). In cultures treated with benzo[a]pyrene (CAS: 50-32-8), which requires a different activation system than that for 4-NQO, UDS was less pronounced. In 9 cell lines the average rates of UDS were inversely related to TGr. Two cell lines showed a different pattern.
Two wearers of soft cosmetic contact lenses developed corneal infection by the protozoa Acanthamoeba. Contact lens solutions were found to be contaminated in both cases. The clinical course and management are described in this report. Factors that may predispose contact lens wearers to infection by Acanthamoeba and preventative measures are discussed.
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Total cellular glycopeptides of 7 human uroepithelial cell lines that differ in the grade of transformation (TGr) were analysed by gel filtration and affinity chromatography on immobilized lectins. The 4 cell lines that are tumorigenic in nude mice and invasive in vitro (TGr III) possess more highly branched, tri- and tetraantennary N-acetyllactosaminic glycans, with less biantennary glycans than the 2 non-tumorigenic, noninvasive (TGr II) cell lines examined. The only exception to this general pattern is the third cell line, which is classified as TGr II. The cellular glycopeptide distribution pattern in this cell line is similar to that of the TGr III cells. The possible relationship between altered glycosylation of membrane glycoproteins and the expression of a malignant phenotype is discussed.
The rationale of the present investigation is the observations made by many authors of changes in the molecular structure of the cell surface during the multistep process of malignant transformation. These changes may influence cell-matrix and cell-cell interactions and thereby cause changes in cell adhesiveness and cell shape. The aim of the present work was to investigate whether the development of various grades of transformation in vivo and in vitro of human urothelial cells is accompanied by significant changes in cell shape as measured by Fourier analysis. The following transformation grades (TGr) have been defined (Christensen et al. 1984; Kieler 1984): TGr I = nonmalignant, mortal cell lines that grow independently of fibroblasts and have a prolonged life span. TGr II = nonmalignant cell lines with an infinite life span. TGr III = malignant and immortal cell lines that grow invasively in co-cultures with embryonic chick heart fragments and possess tumorigenic properties after s.c. injection into nude mice. Comparisons of 4 pairs of cell lines were performed; each pair was of the same origin. Two pairs--each including a TGr I cell line (Hu 961b and Hu 1703S) compared to a TGr III cell line (Hu 961a or Hu 1703He)--were derived from two transitional cell carcinomas (TCC) containing a heterogeneous cell population. Two additional cell lines classified as TGr II (HCV-29 and Hu 609) were compared to two TGr III sublines (HCV-29T and Hu 609T, respectively) which arose by "spontaneous" transformation during propagation in vitro of the respective maternal TGr II-cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
A double-blind, randomized and placebo-controlled study was undertaken to assess the effects of metoprolol on controlled hypotension during halothane anaesthesia. Nineteen patients under-going middle ear or nasal septum surgery were studied. The aim was to achieve a 25% reduction of the mean arterial pressure in both groups. Metoprolol was given by mouth on two occasions in the 10-12 h before operation. In the group pretreated with metoprolol the halothane concentration was reduced by 35.5%. The duration of bleeding and its degree were reduced significantly. The time to awakening was shorter and of better quality after pretreatment with metoprolol. Rate-pressure product was less after pretreatment with metoprolol, and rebound hypertension was well controlled.
The effect of a single treatment with the skin tumor-promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the expression of the cellular proto-oncogenes, c-myc, c-rasHa, c-rasKi and c-fos was examined in the non-tumorigenic human bladder epithelial cell line HCV 29. TPA (1 microgram/ml) increased the transcription of the c-fos gene of HCV 29 at least 50-fold, and this stimulation was observed within minutes. The response was transient, and was accompanied by a rapid and transient change in cell morphology. The expression of c-myc, c-rasHa and c-rasKi were not enhanced by the TPA treatment. These results show that human bladder epithelial cells respond to a known skin tumor-promoter, TPA, by altering the transcription of a specific proto-oncogene in these cells.
Intrathecal and epidural catheters and an intravenous cannula were inserted in 10 goats. After administration of either morphine 4 mg, intravenously, 1 mg intrathecally or 4 and 8 mg epidurally, or fentanyl 0.1 mg intravenously, 0.05 mg intrathecally or 0.1 and 0.2 mg epidurally, venous blood and CSF were sampled at 2, 5, 10, 15, 30 min and 1, 2, 4, 6, 8 and 24 h. The concentrations of the drugs were measured by radioimmunoassay. After administration of intravenous morphine the plasma concentration-time curve fitted a 3-compartment model (body clearance = 84 +/- 23 ml/min/kg, mean +/- s.d., N = 5), while after fentanyl the plasma concentration-time curve was best described by a 2-compartment model (body clearance = 3.9-5.8 ml/min/kg, N = 3]. After intrathecal injection the elimination rates of the opioids from CSF were 0.3 to 2.0 and 0.6 to 2.4 ml/h/kg for morphine and fentanyl, respectively (N = 3). The time to reach maximum CSF concentration after epidural administration was 0.22 +/- 0.14 h for morphine (N = 6) and 0.22 +/- 0.13 h for fentanyl (N = 8). In the same goat the CSF availability was 2.3 and 11.3% for morphine and 0.8 and 3.3% for fentanyl following epidural administration of the low and high doses, respectively. After epidural administration, morphine and fentanyl are absorbed into CSF at the same rate but the relative amount of drug absorbed may be higher for morphine than fentanyl. Bulk flow is supposed to be the principal mechanism of opioid elimination from CSF.
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A comparison of blacks and whites 6 to 49 years old revealed striking differences between races with respect to the prevalence of various dyslipoproteinemias and mean plasma lipid levels. Compared with whites, juvenile and adult blacks of both sexes had higher mean levels of high-density lipoprotein cholesterol (HDL-C), with correspondingly higher prevalences of the hyperHDL and hypoLDL (low-density lipoprotein) phenotypes. In contrast, whites showed a much higher prevalence of type IV hyperlipoproteinemia and higher mean triglyceride levels in most age-sex groups. Although juvenile blacks had higher mean levels of LDL-C than did whites, this race difference was reversed in men, while women showed inconsistent differences between races. Adult black men and juvenile blacks of both sexes had a somewhat higher prevalence of the type IIA phenotype than whites. The distribution of major HDL-C predictors in this population could not account for the difference in prevalence of hyperHDL between races. These findings suggest that health professionals may find differences in plasma lipid and lipoprotein patterns between their black and white patients, but additional research is needed to ascertain the disease risks associated with dyslipoproteinemia among blacks.
Mouse monoclonal antibodies to human urinary bladder carcinoma cells have been examined by indirect membrane immunofluorescence using a panel of 27 human cell lines. Two of the monoclonal antibodies, 7E9 (IgG3) and S2C6 (IgGl), were found to distinguish between urinary bladder carcinoma cells and normal urothelium. The third monoclonal antibody, T24.06.5(IgGl), discriminated among cell lines of urothelial and non-urothelial origin but did not distinguish between urinary bladder carcinoma and normal urothelial cells. None of the of the antibodies was found to be strictly selective, and occasional cross-reactions with unrelated cell types were observed. The monoclonal antibody 7E9, showing the highest degree of selectivity, was further examined by an indirect immunoperoxidase technique on frozen tissue sections from 19 patients. The antibody reacted with all (7/7) bladder carcinomas examined and gave negative results with control normal bladder mucosa (0/8) and unrelated tumor tissue (0/4) sections. The 7E9 antibody was purified by protein A affinity chromatography, labeled with 131I and used for gamma-scintigraphy in nude mice xenografted with human urinary bladder carcinoma T24. The 7E9 antibody was capable of locating the T24 xenografts in nude mice; it localized preferentially in the T24 tissue compared to normal mouse tissues. The T24 xenografts could not be detected by gamma-scintigraphy with 131I-labeled monoclonal antibody against human mammary carcinoma cells and two other control antibodies. Likewise the 131I-labeled 7E9 antibody was not capable of locating human mammary carcinoma xenografts in nude mice.
Selectivity of mouse monoclonal antibody 7E9 (IGG3) directed against human urinary bladder carcinoma cells has been examined by indirect membrane immunofluorescence, using a panel of 31 human cell lines. The 7E9 monoclonal antibody discriminated between urinary bladder carcinoma cells and normal urothelium or cells of non-urothelial origin, although occasional reactions with bladder carcinoma-unrelated cell types were observed. The 7E9 antibody was purified by protein A affinity chromatography, labeled with 131I and used for gamma scintigraphy in nude mice xenografted with human urinary bladder carcinoma T24. The 7E9 antibody was capable of locating the T24 xenografts in nude mice; it localized preferentially in the T24 tissue compared to normal mouse tissues. The T24 xenografts could not be detected by gamma scintigraphy with 131I-labelled monoclonal antibody against human mammary carcinoma cells and two other control antibodies. Likewise, the 131I-labelled 7E9 antibody was not capable of locating human mammary carcinoma xenografts in nude mice.