Stabilization vs. destabilization of G-quadruplex superstructures: the role of the porphyrin derivative having spermine arms.

The interaction of the porphyrin derivative H2TCPPSpm4, having spermine pendants in the four meso positions, with the G-quadruplex (GQ) structure formed by the DNA aptamer TGGGAG has been investigated by means of UV, electronic circular dichroism and PAGE studies. The results reported here demonstrate that the porphyrin derivative is capable of stabilizing or destabilizing the higher-ordered structures of parallel GQs, depending on the method used to reach their relative stoichiometry (titration vs. single addition). Noteworthily, when two equivalents of H2TCPPSpm4 were mixed directly with one equivalent of the (TGGGAG)4 GQ to reach a 2 : 1 H2TCPPSpm4 : GQ ratio T1/2 higher than 80 °C was also observed confirming the presence of higher-ordered GQ structures.

Vortexes tune the chirality of graphene oxide and its non-covalent hosts.

Graphene oxide (GO) is one of the most appealing bidimensional materials able to interact non-covalently with achiral molecules and to act as chiral inducers. Vortexes can tune chirality and, consequently transfer a specific handedness to non-covalent host molecules, either when dispersed in water or when deposited on a solid surface.

A series of cationic sterol lipids with gene transfer and bactericidal activity.

A family of cationic lipids was synthesized via direct amide coupling of spermine to the C-24 position of cholic acid analogs. Four monosubstituted spermines and a bis-substituted spermine were evaluated as plasmid transfection reagents, as bacteriostatic agents, and as bactericidal agents. The incorporation of a double bond in the sterol moiety enhanced transfection efficiency significantly and produced two compounds with little cytotoxicity and transfection potency comparable to Lipofectamine2000. Inclusion of the double bond had no effect on the general trend of increasing bactericidal activity with increasing sterol hydrophobicity. Co-formulation of the most hydrophilic of the compounds with its bis-substituted analogue led to enhancement in transfection activity. The bis-substituted compound, when tested alone, emerged as the most bacteriostatic compound in the family with minimum inhibitory concentrations (MIC) of 4 microM against Bacillus subtilis and 16 microM against Escherichia coli and therapeutic indexes (minimum hemolytic concentration/minimum inhibitory concentration) of 61 and 15, respectively. Cationic lipids can be optimized for both gene delivery and antibacterial applications by similar modifications.

Renal pelvic cancer: a review of 611 patients treated in Illinois 1975-1985. Cancer Incidence and End Results Committee.

Renal pelvic transitional cell carcinoma constitutes about 7 percent of all kidney cancer. This report is a summary of 611 Illinois patients with this tumor treated between 1975 and 1985. Overall, the five-year relative survival rate was 62 percent and the observed five-year rate was 48 percent. Stage was a major determinant of survival, as expected, in these cancer patients. The Illinois experience is reviewed and compared with the accumulated literature experience with renal pelvic cancers since 1944.

Renal pelvic transitional cell carcinoma. The role of the kidney in tumor-node-metastasis staging.

Renal pelvic carcinoma is a rare tumor. There are several staging systems currently in use based on a bladder cancer staging model. An analysis of the American Cancer Society, Illinois Division, experience with 611 cases of renal pelvic transitional cell carcinoma suggested that the kidney parenchyma may be a determinant in the anatomic spread of disease. A tumor-node-metastasis system for renal pelvic (separate from ureteral) cancer is recommended.

Cytogenetic manifestations associated with the reversion, by gene amplification, at the HGPRT locus in V79 Chinese hamster cells.

Some HGPRT spontaneous revertants were isolated from a mutant line (E2) of V79 Chinese hamster cells and phenotypically characterized. Dot-Blot hybridization with a 32P-labelled HGPRT probe revealed an increase in the number of HGPRT sequences in some of these revertants, suggesting the occurrence of gene amplification. Cytogenetic analysis performed in three of these revertants showed a characteristic abnormally banding region (ABR) on the elongated p arm of the X chromosome. In situ hybridization in one revertant (RHE2) showed that the amplified sequences reside on the p+ arm of the X chromosome in two different localizations. Because of the very probably clonal origin of the revertant, these features indicate that the amplified sequences might rearrange after their integration into the chromosome.

Invasive giant condylomata acuminata: a case report.

We report on a patient with invasive giant condylomata acuminata (Buschke-Loewenstein tumor). This tumor is an exophytic human papilloma viral lesion with downward growth without histological malignancy. The aggressive progression of this lesion requires early surgical excision with clear margins. Delay in recognition of this tumor can otherwise lead to a fatal clinical course.

Chromosome aberrations associated with CAD gene amplification in Chinese hamster cultured cells.

Eleven sublines with increasing resistance to N-phosphonacetyl-L-aspartate (PALA) were isolated from the V79,B7 Chinese hamster cell line. Aspartate transcarbamylase activity and CAD gene copy number increased with increasing resistance of sublines. In situ hybridization with a DNA probe for the CAD gene showed that the amplified sequences resided in the terminal region of a marker chromosome with elongated q arms. This region stained homogeneously after G-banding. A high incidence of both numerical and structural chromosome aberrations was found in PALA-resistant cells. In hyperdiploid and polyploid cells, containing 2 copies of the marker chromosome, dicentrics were found at a very high frequency. As indicated by in situ hybridization and G-banding, they originated from a rearrangement involving 2 homologous marker chromosomes.

The in vitro and in vivo effects of extracorporeal shock waves on malignant cells.

The in vitro cytotoxic effect of extracorporeal shock waves (ESW) on renal cell carcinoma (RCC) cells was compared to the effect on normal human embryonic kidney (NHEK) cells. In the in vitro studies cell samples were brought into the second focal point and exposed to different numbers of shock wave impulses. The four parameters of RCC tumor cell injury which were measured, i.e., cell viability, cell growth, cell attachment and electron microscopic evidence of damage, were augmented with increasing SW levels. At 2,000 shock waves (SW) a significant decrease in RCC viability, cell growth and cell attachment was seen compared to the NHEK cells. In the in vivo experiment a FANFT induced bladder tumor was transplanted into the right hind legs of C3H/He mice and the tumors were exposed to 1,400 SW. Preliminary data showed that 1,400 SW at day 12 post transplant significantly inhibited tumor growth. Combining 1,400 SW with cis-diamminedichloroplatinum (4 mg/kg) did not enhance the tumor inhibitory effect of each individually. Doxorubicin (5 mg/kg) and 1,400 SW produced a significant synergistic tumor inhibitory effect.

The effect of verapamil in reducing the severity of acute tubular necrosis in canine renal autotransplants.

Calcium channel blockade has been shown to prevent warm renal ischemic damage. The ability of verapamil to decrease the severity of acute tubular necrosis (ATN) after 24-hr cold storage and autotransplantation was studied in a randomized paired study of 12 dogs. Experimental animals pretreated with intraarterial verapamil and flushing of the harvested kidney with cold intracellular solution containing verapamil demonstrated significantly (P less than .05) greater renal function preservation over their matched controls. A subsequent nonpaired study of 6 dogs treated only with flushing of the harvested kidney with perfusate containing verapamil demonstrated no significant preservation advantage over controls. We conclude that verapamil, administered prior to the ischemic event, can enhance the protective effect of hypothermia and decrease the severity of ATN in ischemically injured kidneys.

Spontaneous perinephric hemorrhage from extrarenal angiomyolipoma.

We believe this is the first reported case of spontaneous perinephric hemorrhage arising from an extrarenal angiomyolipoma. To date there have been no cases reported of extrarenal angiomyolipoma associated with tuberous sclerosis. All extrarenal angiomyolipomas have been benign and treated with simple excision.

Modulation of induced reversion frequency by nucleotide pool imbalance as a tool for mutant characterization.

Addition of thymidine (TdR) or deoxycytidine (CdR) to the culture medium during posttreatment incubation affected the frequency of mutagen-induced reversion in three hypoxanthine-guanine phosphoribosyl transferase-deficient mutants of V79 Chinese hamster cells. With two of the mutants (E20 and I3), reversions induced by N-ethylnitrosourea, ethyl methanesulfonate, and methyl methanesulfonate were enhanced by TdR and were either decreased (E20) or not affected (I3) by CdR. With the third mutant (E21), alkylating agent-induced reversions were enhanced by CdR and decreased by TdR. Finally, 6-amino-2-hydroxypurine induced reversions were enhanced by TdR in mutant I3 and were decreased by TdR or deoxyadenosine (AdR) and enhanced by CdR in mutant E21. An attempt was made to reconcile these results with simple mutation mechanisms, based on either G:C to A:T or A:T to G:C transitions. It is suggested that the present approach may add useful information to studies of specific revertibility of mammalian cell mutants with known mutagens.

Cytomegaloviral epididymitis in a patient with the acquired immune deficiency syndrome.

We report on a patient with cytomegaloviral epididymitis and the acquired immune deficiency syndrome. The diagnosis was suggested by epididymitis that was refractory to antibiotics, and by isolation of cytomegalovirus from the urine and semen. The definitive diagnosis was made with immunohistochemical staining for cytomegaloviral antigens in the epididymal ductal cells. Because of the ineffectiveness of antimicrobial agents in this disorder, epididymectomy is the current treatment of choice.

Anti-inflammatory drugs in experimental atherosclerosis. Part 5. Influence of cortisone acetate on short-term and long-term cholesterol fluxes in atherosclerotic aorta.

Previous studies in this series have shown that cortisone and other anti-inflammatory drugs inhibit atherosclerotic plaque development in cholesterol-fed rabbits. The present study was designed to investigate the influence of cortisone on the processes of cholesterol influx and efflux in the aorta wall. Forty-seven New Zealand white rabbits were fed a 1% cholesterol diet for periods up to 12 weeks. In addition 23 of the animals were fed 5 mg cortisone acetate daily. At 0, 5 and 12 weeks, groups were fed a tracer dose of [3H]cholesterol. Plasma cholesterol specific radioactivity was measured at intervals during the next 10 days. Total aorta cholesterol and its specific activity were measured by killing groups of animals at 2 days and 10 days. Atherosclerotic plaque intensity at 12 weeks, measured planimetrically, averaged 68 +/- 12% in controls vs. only 6 +/- 3% in cortisone-treated animals. During the period between 5 and 12 weeks, net cholesterol accumulation by chemical analysis averaged only 11 micrograms/g aorta/day in cortisone-treated animals vs. 117 micrograms/g in controls. [3H]cholesterol influx (measured during a brief 2-day exposure) at 5 weeks averaged 206 and 199 micrograms/g tissue/day and at 12 weeks 586 micrograms and 281 micrograms/day in control and cortisone-treated animals, respectively. Measured over a longer 10-day period, however, the apparent influx of [3H]cholesterol was much less in cortisone-treated animals, averaging only 53 micrograms/day compared to 269 micrograms/day in controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Recovery of V79 cell clones with different phenotypes in aminopterin- or azaserine-containing media used for the selection of HGPRT revertants.

Three 6-thioguanine (6TG)-resistant mutants were mutagen-treated and selected for clones capable of growing in 2 selective media: HAT medium, containing aminopterin (AP) and HAS medium, containing L-azaserine (AS). Both 6TG-sensitive, wild-type clones and 6TG-resistant mutants were found among colonies growing in HAT medium, while only 6TG-sensitive clones grew in HAS medium. Time for expression was required by 6TG-resistant but not by 6TG-sensitive clones, that were fully expressed immediately after treatment. All HAT-resistant, 6TG-resistant clones which were analyzed proved to be resistant to AP. These data were interpreted as follows: in HAT medium, both HGPRT+ revertants and double mutants (HGPRT-, AP-resistant) were selected, while only HGPRT+ revertants were selected in HAS medium. Not all 6TG-resistant mutants were able to produce both classes of HAT-resistant clones.

Instantaneous renal arterial pressure-flow relations in anesthetized dogs.

Instantaneous renal arterial pressure-flow (P/ Qra ) relations were investigated in 11 anesthetized dogs using the nonpulsatile fall in aortic pressure and renal arterial flow ( Qra ) during cardiac arrest caused by vagal stimulation. We found that P/ Qra relations were linear with an extrapolated zero flow intercept (Ped, effective downstream pressure) of 20.8 +/- 1.9 mmHg and the reciprocal of the slope (Ra, arterial resistance) of 0.6 +/- 0.04 mm Hg X ml-1 X min. These values are markedly lower than the values found in similar experiments in coronary and femoral arteries. Raising renal venous pressure (5 dogs) decreased Qra and elevated Ra and Ped in the ipsilateral renal artery while decreasing Qra and elevating Ra but not Ped in the contralateral renal artery. Carotid artery occlusion (6 dogs) decreased Qra and elevated Ra and Ped. Alpha-Adrenergic blockade (4 dogs) lowered Ped and Ra. Arterial resistance seems to be more important for change in P/Q relations in the renal arterial bed than it is in other arterial beds investigated so far. We suggest that the effective downstream pressure to renal arterial flow is downstream from the glomerular capillaries. The location of the "vascular waterfall " phenomenon appears to be between the intrarenal veins and the veins outside the capsule.

Selection in HAT medium is not a reliable method for the study of reversion from 6-thioguanine resistance to sensitivity.

6-Thioguanine-resistant mutants were induced in V79 Chinese hamster cells with 2-aminopurine, ICR-170 and hycanthone. Samples of mutants of different origin were treated with EMS or 1CR-170 and plated in HAT medium for selection of revertants. In the result, a significant fraction of HAT-resistant clones was not 6-thioguanine-sensitive as would have been expected from a genuine reversion to wild type.

Plasmid-dependent co-mutation in Streptomyces coelicolor A3(2).

A spontaneous chromosomalmutation(plc A(-)) in Streptomyces coelicolor A3(2) made the inborn plasmid SCP1 susceptible to curing by UV irradiation. Lack of the SCP1 plasmid (in SCP1(-) strains) prevented the occurrence of the co-mutation process after MNNG treatment, although it left the susceptibility to the lethal effect of the mutagen virtually unaffected. SCP1(-) strains were, however, ultrasensitive to the lethal effect of UV. Curing a plc A(-) strain of its SCPI plasmid made it refractory to co-mutation by MNNG and sensitive to the lethal effect of UV; reinfected by the plasmid, the strain resumed both the co-mutation proficiency and the UV-resistance. The occurrence on the SCP1 plasmid of a gene comparable to the uvrE gene of E. coli (Nevers and Spatz 1975) was assumed.