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Biomedical subjects

D Venzon

Publications and source records attributed to D Venzon.

103 records · Page 6Linked to original sources
PubMed1991

Diurnal variation and left-right distribution of pyroglutamyl peptidase I activity in the rat brain and retina.

The thyroliberin and luliberin contents exhibit a diurnal rhythm within the brain and an asymmetrical distribution of both neuropeptides has been demonstrated in the hypothalamus. Since they have been described as substrates of pyroglutamyl peptidase I, this activity was analysed in several rat brain regions and other structures, in order to investigate its putative diurnal variations and changes in relation to the distribution of these neuropeptides and/or other susceptible substrates. Fluorometric activity was assayed in the retina, pituitary gland, superior cervical ganglia, pineal gland, some selected brain regions, and serum of adult male rats at six different time points of a 12:12 h light:dark cycle, using pyroglutamyl-beta-naphthylamide as substrate. A significant circadian rhythm was demonstrated in the retina, the hypothalamus, and the intermediate-posterior pituitary lobe. In addition, a small but significant asymmetrical distribution of this activity, at certain time points, was disclosed: The activity was higher in the left than in the right retina at 10 h of the light period, whereas it was predominant in the right side at 01 h of the dark period. Furthermore, the activity was higher in the left anterior than in the right hypothalamic area at 13 and 01 h. These results could be indicative of a role of this enzymatic activity in the control of the functional status of its endogenous substrates.

Animals↗
PubMed1991

Circadian rhythm in Leu-beta-naphthylamide hydrolysing activity in selected photoneuroendocrine areas of adult male rats.

Soluble Leu-beta-naphthylamide hydrolysing activity (arylamidase activity) was assayed in retina, superior cervical ganglia, several brain areas and serum of adult male rats, at different time points of a 12:12h light:dark cycle (from 7h to 19h light). The results demonstrated a left or right biased asymmetrical distribution of this activity depending on the time point studied: While the levels of activity were significantly higher in the left retina than in the right one at 10h of the light period, these were predominant in the right side, at 01h of the dark period. In addition, this activity was higher in the left hypothalamus at 13h of the light period. No asymmetries were disclosed in the rest of time points and structures studied. On the other hand, this activity demonstrated a diurnal variation in the left anterior hypothalamus and total posterior hypothalamus but no periodic variation was evidenced in right anterior hypothalamus or the rest of zones studied. These results may reflect the role of this activity regulating the functional status of its susceptible endogenous substrates.

Animals↗
PubMed1991

Photodynamic therapy of oncogene-transformed cells.

Photodynamic therapy with dihematoporphyrin ether sensitizes malignant cells to damage by 630 nm light. The in vitro, in vivo photodynamic therapy sensitivity of a cell line transformed by the Kirsten ras oncogene (45342) was studied to establish a new photodynamic therapy model. With the colony formation assay, neither light alone nor dihematoporphyrin ether alone affected 45342 survival. Energy-dependent photodynamic therapy effects were seen in vitro in dihematoporphyrin ether-incubated and light-exposed cells (90% cytotoxicity = 950 joules/m2; 99% cytotoxicity = 1575 joules/m2; p2 less than 0.05). Subcutaneous allografts of 45342 were established in nu/nu mice, and ideal route (intravenous or intraperitoneal) of dihematoporphyrin ether delivery, dihematoporphyrin ether tissue kinetics, and in vivo photodynamic therapy effects were examined. Intravenous administration not only gave higher levels of the sensitizer in various tissues, but also was associated with less variation than the intraperitoneal route. Selective dihematoporphyrin ether retention was documented in the tumors at 24 hours after injection compared with other tissues, and photodynamic therapy with 0.3 W/cm2 to a total dose of 150 joules/cm2 led to progressive coagulative tumor necrosis and tumor regression. These studies confirm that transformed, malignant cells are sensitive to photodynamic therapy, and this model may prove in future studies to increase efficacy to photodynamic therapy (i.e., with dihematoporphyrin ether delivery by monoclonal antibodies).

Animals↗
PubMed1990

Effects of tumor necrosis factor, alone or in combination with topoisomerase-II-targeted drugs, on human lung cancer cell lines.

Tumor necrosis factor alpha (TNF) exhibits cytotoxic activity on some solid tumors and has been reported to be synergistic with topoisomerase-II-targeted antineoplastic agents. A wide range of TNF concentrations (from 10 to 10,000 U/ml) was tested in 9 human lung cancer cell lines (5 small-cell and 4 non-small-cell carcinomas) using a semi-automated MTT assay. TNF was not cytotoxic in 8 cell lines, while an adenocarcinoma cell line was marginally sensitive to the cytokine. Using 125I-TNF we were able to show the presence of specific binding sites for TNF in 4/9 human lung cancer cell lines. Scatchard analysis of the marginally sensitive cell line showed high-affinity, saturable binding. With 5 cell lines we also tested whether TNF affected the cytotoxicity of doxorubicin and etoposide, 2 topoisomerase II-targeted drugs which are widely used in the therapy of lung cancer. No significant increase in cytotoxicity was seen when TNF was added to the 2 anti-neoplastic agents. In contrast to certain other human and mouse lines, human lung cancer cell lines appear to be resistant to TNF, despite the presence of the receptor in some of them; moreover, no synergistic effect of TNF and 2 topoisomerase-II-targeted drugs was evident in these human cell lines.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Prolonged survival of tumor-bearing rats with repetitive low-dose recombinant tumor necrosis factor.

Tumor necrosis factor may be a mediator of the syndrome of cancer cachexia. Tachyphylaxis or tolerance to the cachectic effects of recombinant tumor necrosis factor (rTNF) has been previously described. In this study, we investigate whether repetitive exposure to rTNF can induce similar tolerance in tumor-bearing (TB) rats and ameliorate cachexia induced by the tumor. In experiment 1, non-tumor-bearing (NTB) and TB rats were randomized to either escalating low doses of rTNF or saline i.p. twice daily for 9 consecutive days. NTB rats treated with rTNF demonstrated a significant decline in food intake and weight change (P less than 0.00001) but soon developed tolerance to the cachectic effects of rTNF; they consumed significantly more food than on the first day of treatment and had weight change similar to NTB rats treated with saline. TB rats treated with rTNF showed a similar significant decline in food intake and weight change (P less than 0.0001) and also demonstrated similar tolerance to the cachectic effects of rTNF with continued treatment. Following treatment, TB rats that had been treated with rTNF ate significantly more and lost less weight than TB rats that had been treated with saline (P less than 0.00001). rTNF treatment of TB rats also demonstrated antineoplastic activity, as estimated tumor weight of tumors from rats treated with rTNF were significantly less than controls (P = 0.003). The anticachexia and antineoplastic effects of rTNF resulted in prolonged survival of TB rats treated with rTNF compared to control TB rats (P = 0.015). Experiment 2 utilized two different rTNF treatment regimens in TB rats: one group received 12 days of escalating doses of rTNF, and another group received 15 days of rTNF treatment. TB rats treated with rTNF again had a significantly greater food intake (P less than 0.00001) and delayed weight loss (P = 0.0001) posttreatment that was further augmented by additional doses of rTNF. Antineoplastic activity of rTNF was less clear, and overall tumor growth curves were not affected by rTNF treatment. Survival of TB rats treated with rTNF was again significantly increased in a dose-dependent manner (P = 0.006). Repeated administration of low doses of rTNF to TB rats induces mild reduction in tumor growth, tolerance to the cachectic effects of rTNF that results in tolerance to the cachectic effects of tumor, and prolongation of survival.

Animals↗
PubMed1990

Survival after surgical resection for high-grade chest wall sarcomas.

Indications for chest wall resection of metastatic or locally recurrent sarcoma and for subsequent bony reconstruction are controversial. Twenty-eight patients had chest wall resection for high-grade primary, metastatic, or recurrent sarcoma. In all patients, resection with selective reconstruction of the bony thorax was performed without operative mortality. Since 1980, only patients with four or more ribs resected have had selective bony reconstruction. Follow-up ranged from 8 to 132 months (median follow-up, 42 months). All deaths were related to sarcoma recurrence. The overall actuarial survival rate was 85% at 1 year, 65% at 3 years, and 59% at more than 5 years. The overall actuarial proportion without disease recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years. There was no significant difference in overall or disease-free survival for patients with primary, metastatic, or recurrent tumors. The most important prognostic factors were positive margins and concomitant pulmonary resection for synchronous lung metastases. These data support aggressive resection to obtain pathologically tumor-free margins for chest wall sarcomas, whether primary, metastatic or recurrent. Reconstruction can be individualized based on the extent of resection.

Adolescent↗
PubMed1990

Correlation of in vitro drug sensitivity testing of long-term small cell lung cancer cell lines with response and survival.

In vitro drug sensitivity testing (DST) of long-term cultures from small cell lung cancer (SCLC) tumours was correlated with response and survival after four cycles of etoposide and cisplatin. 27 cell lines from 25 patients were tested by the semi-automated MTT assay after a median culture of 29 months. The logs of the IC50 concentrations for etoposide and cisplatin were correlated with each other. For both drugs, median IC50 values of patients with partial or complete responses ("responders") were significantly lower (7-8 fold) than those of non-responders. When survival was plotted according to whether drug IC50 values were in the upper or lower halves, curves for etoposide were significantly different, but those of cisplatin were not. DST of the long-term cell lines by MTT assay was significantly correlated with the Weisenthal dye exclusion assay of earlier passages of the same cell lines. DST of long-term SCLC cultures can predict clinical response and, for etoposide, survival. Disease-oriented panels of carefully selected, continuous, human tumour cell lines can be used to screen new drugs.

Carcinoma, Small Cell↗
PubMed1990

Effects of antifungal agents on the function of human neutrophils in vitro.

Polymorphonuclear leukocytes (PMNs) are an important component of the host defense against fungi. We investigated the influence of five antifungal agents on PMN function and compared them with amphotericin B (AmB). The in vitro effects of AmB, flucytosine, ketoconazole, fluconazole, Sch-39304, and cilofungin (LY121019) on chemotaxis, phagocytosis, oxidative metabolism of PMN as reflected by superoxide anion (O2-) generation, and intracellular killing of Candida albicans blastoconidia were examined. With regard to chemotaxis in response to N-formylmethionyl-leucyl-phenylalanine, as measured by the multiwell chamber method, AmB induced a marked decrease (greater than or equal to 5 micrograms/ml), whereas ketoconazole at 5 micrograms/ml enhance it. Phagocytosis was significantly decreased after pretreatment of PMNs with AmB and Sch-39304 (greater than 5 and 1 to 10 micrograms/ml, respectively). O2- production after stimulation of PMNs with N-formylmethionyl-leucyl-phenyl-alanine was significantly decreased by AmB (greater than 5 micrograms/ml) and enhanced by Sch-39304 (1 to 5 micrograms/ml). In contrast, intracellular killing, as tested by methylene blue staining, was enhanced by ketoconazole (5 micrograms/ml) and Sch-39304 (1 to 5 micrograms/ml). Flucytosine, fluconazole, and cilofungin did not affect PMN function at therapeutic concentrations. The results of this comprehensive study indicate that AmB, flucytosine, cilofungin, and the newer azoles, at safely achievable concentrations, generally do not suppress PMN function at therapeutic enhance selective functions.

Antifungal Agents↗
PubMed1990

Effects of antiretroviral dideoxynucleosides on polymorphonuclear leukocyte function.

Dideoxynucleosides (zidovudine[AZT], dideoxycytidine[ddC], and dideoxyinosine[ddI]) are promising new agents for the management of human immunodeficiency virus type 1 (HIV-1) infections. In light of recent data demonstrating defects in the polymorphonuclear leukocyte (PMN) bactericidal activity of HIV-1-infected patients and since many chemotherapeutic agents affect PMN function, we examined their effects on the function of PMNs from both healthy and HIV-1-infected individuals in vitro. AZT (0.1 to 25 microM), ddC (0.01 to 1 microM), and ddI (0.2 to 50 microM) had no effect on viability, chemotaxis to N-fromylmethionyl leucyl phenylalanine, phagocytosis of Candida albicans or Staphylococcus aureus, or superoxide production following stimulation by N-formylmethionyl leucyl phenylalanine. Killing of C. albicans was not affected by AZT but was enhanced by 0.1 and 1 microM ddc (a 1 microM, killing was 26.0 +/- 2.02% compared with 17.0 +/- 0.73% for controls: P = 0.006) and 0.2 to 50 microM ddI (at 10 microM, killing was 25.0 +/- 0.68% compared with 17.8 +/- 0.91% for controls; P = 0.002). Killing of S. aureus was unchanged by AZT and ddC but was significantly enhanced by ddI at 0.2 to 20 microM (at 2 microM, killing was 71.2 +/- 5.57% compared with 51.4 +/- 6.29% for controls; P = 0.0045). In addition, the preexisting defective bactericidal capacity of PMNs from HIV-1-infected patients was enhanced by ddI (P less than 0.025). Potential enhancement by these dideoxynucleosides of certain PMN functions of HIV-1-infected patients deserves further study.

Cell Survival↗
PubMed1990

Subcellular distribution of soluble and membrane-bound Leu-, Arg- and Asp-beta-naphthylamide-hydrolysing activities in rat brain.

Subcellular distribution of soluble and membrane-bound Leu-, Arg- and Asp-beta-naphthylamide hydrolysing activities (arylamidase activity) was studied from left and right rat brains, each including hemisphere, cerebellum and brain stem. Both soluble Leu- and Arg-beta-naphthylamide hydrolysing activities showed the highest levels in the synaptosomal fraction. However, the microsomal fraction presented the highest levels when membrane-bound activity was assayed. When we used Asp-beta-naphthylamide as substrate, there were no differences among fractions in the membrane-bound activity, and the highest soluble activity was present at the mitochondrial level. Two different patterns in the subcellular distribution of enzymatic activity were observed: One of them was the result of the use of Leu- or Arg-beta-naphthylamide as substrate and the other when Asp-beta-naphthylamide was employed. No differences between left and right brains in soluble or membrane-bound activities were found.

Aminopeptidases↗
PubMedDate not supplied

Metastatic melanoma: correlation of MRI characteristics and histopathology.

To correlate the findings on MRI with histopathology of metastatic melanoma, MRI was performed on 29 patients with 36 lesions, using spin-echo and inversion recovery sequences. Histopathologic examination of lesions was performed within 4 weeks of imaging. Lesions were categorized according to cell type and were also evaluated for the presence and extent of melanin, iron, and necrosis. These data were then correlated with the signal intensities of the lesions. Enhancement of lesions after injection of intravenous gadolinium was calculated and correlated to vascularity of the tumor. Melanin was present more frequently in lesions appearing hyperintense or with mixed signal intensity (12/15) than in those appearing hypo- or isointense (6/21) on the T1-weighted sequence. This trend was significant (P = .013). Also, more lesions appearing mixed, ie, having both hypo- and hyperintense components, contained melanin (15/23), as opposed to lesions that appeared to be only hyperintense (3/13) on the STIR sequence. There was no clear association between signal intensity and melanin content on the T2-weighted sequence. There was no significant association between the signal intensities on the MR images and the iron content, tumor size, or tumor cell type of these lesions. There was no clear association between enhancement after gadolinium injection and vascularity, as assessed by histology. The authors concluded in this study that T1 shortening and hypointensity on the STIR sequence seen in patients with metastatic melanoma are most closely related to the melanin content of the tumor.

Adult↗