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At least 199 records · Page 11Linked to original sources
PubMed1986

Chemotherapeutic effects of 13 nitrosoureas on the LSA lymphoma ascites tumor of the C57BL mouse.

The LSA lymphoma of the C57BL/ym mouse has been used to test 13 nitrosoureas for cure of advanced tumors and for induced tumor resistance (ITR) of surviving animals. Tumors were initiated by intraperitoneal inoculation of 10(6) LSA cells. Controls died in 8-9 days. Five-day old tumors were defined as advanced tumors, and treatment consisted of a single dose of a nitrosourea to groups of 10 male mice, 8-9 weeks old, for each compound. The nitrosoureas used were: BCNU (NSC-40992), CCNU (NSC-79037), MeCCNU (NSC-95441), chlorozotocin (CLZ) (NSC-178248), streptozotocin (STZN) (NSC-85998) CNU (NSC-47547), FCNU (NSC-87974), GANU (NSC-254174), ACNU (NSC-245382), PCNU (NSC-95466), cis-acid (NSC-153174), 153174), NSC-88104, and GCNU (NSC-114460). The major endpoint assessed was tumor cure and was grouped as follows: (1) high (greater than or equal to 80%), achieved with BCNU, MeCCNU, CCNU, CLZ, ACNU, FCNU, PCNU, and cis-acid; (2) medium (40- less than 80%), obtained with GANU, NSC-88104, and GCNU, and (3) low or nil (less than 40%), shown by CNU and STZN. The second endpoint was treatment-induced ITR. Cured mice, i.e., those surviving over 30 days after death of controls were challenged with 10(5) LSA live cells, and survivors from this challenge were challenged with 10(7) LSA cells 1 month later. Survivors from both inocula were considered highly immune (HI). High percentages of HI mice (greater than or equal to 80%) were obtained from mice cured with MeCCNU, CCNU, ACNU, FCNU, PCNU, and NSC-88104. STZN produced 0.0% cures; the other nitrosoureas showed 33.3-75% HI mice. Cure rates and ITR appeared to be agent- and structure-related. Cure alone did not lead to the resistant state.

Animals↗
PubMed1999

Concentration tuning mediated by spare receptor capacity in olfactory sensory neurons: A theoretical study.

The olfactory system is capable of detecting odorants at very low concentrations. Physiological experiments have demonstrated odorant sensitivities down to the picomolar range in preparations from the sensory epithelium. However, the contemporary model for olfactory signal transduction provides that odorants bind to olfactory receptors with relatively low specificity and consequently low affinity, making this detection of low-concentration odorants theoretically difficult to understand. We employ a computational model to demonstrate how olfactory sensory neuron (OSN) sensitivity can be tuned by modulation of receptor-effector coupling and/or by other mechanisms regulating spare receptor capacity, thus resolving this conundrum. The EC10-90 intensity tuning ranges (ITRs) of whole olfactory glomeruli and postsynaptic mitral cells are considerably broader than the commensurate ITRs of individual OSNs. These data are difficult to reconcile with certain contemporary hypotheses that convergent OSNs in mammals exhibit a homogeneous population of olfactory receptors and identical tuning for odor stimuli. We show that heterogeneity in spare receptor capacities within a convergent OSN population can increase the ITR (EC10-90) of a convergent population of OSNs regardless of the presence or absence of a diversity of receptor expression within the population. The modulation of receptor-effector coupling has been observed in OSNs; other mechanisms for cellular regulation of spare receptor capacity are also highly plausible (e.g., quantitative regulation of the relative expression levels of receptor and effector proteins). We present a model illustrating that these processes can underlie both how OSNs come to exhibit high sensitivity to odorant stimuli without necessitating increased ligand-receptor binding affinities or specificities and how a population of convergent OSNs could exhibit a broader concentration sensitivity than its individual constituent neurons, even given a population expressing identical odorant receptors. The regulation of spare receptor capacity may play an important role in the olfactory system's ability to reliably detect low odor concentrations, discriminate odor intensities, and segregate this intensity information from representations of odor quality.

Algorithms↗
PubMed1998

Comparison of the E test with broth microdilution for antifungal susceptibility testing of yeasts.

The susceptibilities of 26 recent invasive clinical isolates to amphotericin B (AMP), 5-flucytosine (5FC), fluconazole (FLU) and itraconazole (ITR) were determined by a broth microdilution modification of the NCCLS M27P method and also by E test. Using breakpoint criteria each result was classified as either sensitive (S), intermediate (I) or resistant (R). Taking the optical density (OD)80 as the standard, the results were further classified into major (M) or minor (m) errors. E test: AMP = 0M 0m, 5FC = 0M 5m, FLU = 1M 12m, ITR = 1M 5m errors. Minimal inhibitory concentrations (MIC): AMP = 0M 2m, 5FC = 0M 0m, FLU = 3M 4m, ITR = 1M 7m errors. The E test was quick and relatively simple to perform. Results using the E test compared favourably with those of the OD80 and it should be suitable for the routine susceptibility testing of yeasts to antifungal agents.

Amphotericin B↗
PubMed2003

The combined effect of topical CX-659S, a novel diaminouracil derivative, with topical corticosteroid on the three types of allergic responses in mice or guinea pigs.

CX-659S ((S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4(1H,3H)-pyrimidinedione), a newly discovered anti-inflammatory compound, exerts inhibitory effects against picryl chloride-, oxazolone-, and dinitrochlorobenzene-induced acute contact hypersensitivity responses (CHRs) characterized by Th1-type reactions. Furthermore, this compound suppressed chronic CHRs characterized by Th2-type reactions, which is well known to mimic many, if not all, events occurring within the lesional skin of patients with atopic dermatitis (AD). The present study was conducted to determine the combined effect of topical CX-659S with topical corticosteroid on immediate type (ITR), late type (LTR), and delayed type hypersensitivity (DTHR) allergic reactions that are involved in AD. An ineffective dose of CX-659S (0.03 mg/ear) combined with betamethasone valerate (BV) significantly potentiated inhibitory activity of BV alone (0.1 micro g/ear and 0.3Shizuokag/ear) on both the ITR and the LTR in mice with the ovalbumin (OVA)-induced biphasic cutaneous reaction. Furthermore, the combined effect of CX-659S with BV was also observed on dinitrochlorobenzene (DNCB)-induced DTHR in guinea pigs. These results indicate that CX-659S has a combined effect with corticosteroids on every ITR, LTR, and DTHR. Proper treatment with corticosteroids for a safe and effective treatment of AD is needed. Thus, the combination therapy of topical CX-659S with topical corticosteroid would be one of the potential approaches for devising a proper treatment with corticosteroids.

Administration, Topical↗
PubMedDate not supplied

Isolated testicular relapse in acute lymphoblastic leukemia - effective treatment with the modified CCG-112 protocol.

BACKGROUND: The testes have been considered a sanctuary site for leukemic cells and testicular relapses used to account for a major proportion of the poor outcome of boys with acute lymphoblastic leukemia. With use of aggressive chemotherapy which includes intermediate or high dose methotrexate, the incidence of testicular relapses has declined. However once these patients have received cranial irradiation as a part of the front line protocol, high dose methotrexate needs to be avoided because of risk of developing leucoencephalopathy. AIM: To study the use of non cross resistant chemotherapeutic agents along with a regimen containing lower doses of methotrexate in patients of isolated testicular relapse (ITR). MATERIALS AND METHODS: This is a retrospective analysis of 12 consecutive patients with ITR treated with modified version of the CCG-112 protocol which consists of intensive systemic chemotherapy, cranial chemoprophylaxis along with testicular irradiation. RESULTS: One patient died of regimen related toxicity. Two patients relapsed in the bone marrow during maintenance. Of the nine patients who completed treatment, eight are alive and in remission. One patient had a bone marrow relapse two months after completing treatment. The Kaplan Meier estimates give us an Event Free Survival (EFS) of 66.7% at 10 yrs. CONCLUSIONS: Thus, though the incidence is very low, patients with ITR should be treated aggressively since they have an excellent chance of achieving a long term EFS.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

An experimental method for the percutaneous induction of a posterolateral infarct and functional ischemic mitral regurgitation.

BACKGROUND AND AIM OF THE STUDY: Appropriate experimental models are needed to study the mechanisms underlying left ventricular (LV) remodeling and functional ischemic mitral regurgitation (IMR). Herein is described an original percutaneous method for inducing a well-defined posterolateral infarct and significant IMR. METHODS: Under videofluoroscopic guidance, the second (OM2) and third (OM3) obtuse marginal branches of the circumflex artery of six sheep were selectively and sequentially injected with 100% ethyl alcohol. Transthoracic echocardiography (TTE) was performed before and after alcohol injection, and weekly until sacrifice at 8 +/- 1.3 weeks. The LV endsystolic (LVESD) and end-diastolic (LVEDD) dimensions, interpapillary distance (M1-M2), mitral annulus diameter (MA), and degree of IMR and ischemic tricuspid regurgitation (ITR) were measured. RESULTS: One animal died from irreversible ventricular fibrillation. In the remaining sheep, a well-defined posterolateral infarct of 22% of the heart mass resulted, followed by 2.8 + IMR and 2.1+ ITR. The mean weight gain was 16%, and all sheep showed signs of heart failure. All echocardiographic parameters were increased: systolic MA by 29%, diastolic MA by 18%, LVEDD by 33%, LVESD by 62%, M1-M2 diastolic by 32%, M1-M2 systolic by 21%, and tethering and tenting distances by 32% and 108%, respectively. CONCLUSION: The percutaneous selective injection of 100% ethyl alcohol in OM2 and OM3 resulted in a well-defined posterolateral infarct and significant IMR and ITR. Because it was a percutaneous procedure, this novel, simple and reproducible method did not require a thoracotomy. This model should facilitate the further study of LV remodeling and IMR.

Animals↗
PubMedDate not supplied

Comparison of in vitro drug sensitivity by inhibition of tritium release from [5-3H]-2'-deoxyuridine and a clonogenic assay.

In a search for a rapid and simple method to determine drug-induced cell lethality, the inhibition of tritium release from [5-3H]-2'-deoxyuridine (ITR) was compared with a standard clonogenic assay. Seven drugs were studied. After a 4 hr incubation period, [5-3H]-2'-deoxyuridine was added to cultures of human colon carcinoma cells (HCT-8) in vitro and four dose-response curves were generated for each drug by sampling the culture medium for tritiated H2O formation 4, 24, 48 and 72 hr later. These curves were compared to those obtained by a standard clonogenic assay. The ED50 values for 5 of the 7 drugs tested, methotrexate, 5-fluorouracil, doxorubicin, vincristine and cisplatin, as measured by inhibition of HCT-8 colony growth, were within 3 times the values observed with the metabolic assay. The ITR highly overestimated the cytotoxicity of 5-fluoro-2'-deoxyuridine: the irreversible inhibition of thymidylate synthase by this nucleoside resulted in an ED50 value 100-fold lower than that observed with the clonogenic assay. Opposite results were obtained with 5-fluorouridine. These data indicate that the ITR can be used to determine drug sensitivity of these cells to a host of compounds although it cannot be used indiscriminately for every antineoplastic agent as a cytotoxicity assay.

Adenocarcinoma↗
PubMed1985

Acceleration of neoplasms of reticular tissue with syngeneic thymic graft under renal capsule and gamma radiation.

Weanling ICRC female mice were given syngeneic neonatal thymus graft under renal capsule and two weeks later whole-body gamma-radiation (group ITR). The findings on ITR were compared with three controls--untreated (C), thymus grafted (IT) and irradiated (IR). In ITR group 15/15 developed generalized neoplasms of reticular tissue at 5 to 8 months and single mammary tumor at 7 months. In IR group 12/13, 21/25 in IT and 5/23 in C had neoplastic changes at 7-month onwards. Microscopically these neoplasms had diffuse or focal proliferation of modified reticulum cells, histiocytes, lymphocytes and giant cells. Localized thymic tumors showed either the same picture or prominence of small lymphocytes. Mammary tumors developed in 12/25 IT, and 8/25 in C and nil in IR.

Animals↗
PubMed1998

French previously untreated patients with severe hemophilia A after exposure to recombinant factor VIII : incidence of inhibitor and evaluation of immune tolerance.

Fifty French previously untreated patients with severe hemophilia A (factor VIII < 1%), treated with only one brand of recombinant factor VIII (rFVIII), were evaluated for inhibitor development, assessment of risk factors and outcome of immune tolerance regimen. The median period on study was 32 months (range 9-74) since the first injection of rFVIII. Fourteen patients (28%) developed an inhibitor, four of whom (8%) with a high titer (> or = 10 BU). All inhibitor patients but one continued to receive rFVIII either for on-demand treatment or for immune tolerance regimen (ITR). Among these patients, inhibitor was transient in 2 (4%), became undetectable in 6 and was still present in 6. The prevalence of inhibitor was 12%. Presence of intron 22 inversion was found to be a risk factor for inhibitor development. Immune tolerance was difficult to achieve in our series despite a follow-up period of 16 to 30 months: immune tolerance was complete in only one out of the 3 patients undergoing low dose ITR and in one out of the 5 patients with high dose ITR.

Child↗
PubMed2003

Cation effects on swelling of kappa-carrageenan: a photon transmission study.

Swelling behavior of kappa-carrageenan gels in water and KCl solutions was investigated by photon transmission experiments following the preparation of gels in the presence and absence of externally added K+ ion as a gel promoting agent. Transmitted photon intensity, Itr, increased continuously during swelling depending on the carrageenan and ion content in the gel. This increase in Itr was modeled using the Li-Tanaka equation. Both the experimental work and the model showed that the swelling of low carrageenan and ion content gels took less time than that of high ion content gels. It is confirmed that double helices in a swollen gel move much faster in pure water than in KCl solution during swelling processes. Swelling time constants, tau1, and collective diffusion coefficients, Do, were measured for the gels swollen in water and KCl solutions.

Carrageenan↗
PubMed1985

The origin of adenovirus DNA replication: minimal DNA sequence requirement in vivo.

Adenovirus mini-chromosomes which contain two cloned, inverted adenovirus termini replicate in vivo when supplied with non-defective adenovirus as a helper. This system has been used to define the minimum cis acting DNA sequences required for adenovirus DNA replication in vivo. Deletions into each end of the adenovirus inverted terminal repeat (ITR) were generated with Bal31 exonuclease and the resulting molecules constructed into plasmids which contained two inverted copies of the deleted ITR separated by the bacterial neomycin phosphotransferase gene. To determine the effect of the deletion in vivo plasmids cleaved to expose the adenovirus termini were co-transfected with adenovirus type 2 DNA into tissue culture cells. The replicative ability of the molecules bearing adenovirus termini was assayed by Southern blotting of extracted DNA which had been treated with DpnI, a restriction enzyme which cleaves only methylated and therefore unreplicated, input DNA. Molecules containing the terminal 45 bp of the viral genome were fully active whereas molecules containing only 36 bp were in-active in this assay. Therefore sequences required for DNA replication are contained entirely within the terminal 45 bp of the viral genome. Thus, both the previously described highly conserved region (nucleotides 9-18) and the binding site for the cellular nuclear factor I (nucleotides 19-48) are essential for adenovirus DNA replication in vivo.

Adenoviruses, Human↗
PubMed2005

The DNA minor groove binding agents Hoechst 33258 and 33342 enhance recombinant adeno-associated virus (rAAV) transgene expression.

BACKGROUND: Recombinant adeno-associated viruses (rAAV) are commonly used in pre-clinical and clinical gene transfer studies. However, the relatively slow kinetics of rAAV transgene expression complicates in vitro and in vivo experiments. METHODS: 293 and COS-1 cells were transduced with rAAV2-EGFP, rAAV1-EGFP, or rAAV5-EGFP. The rAAV-EGFP expression was analyzed in the presence of Hoechst 33 258 or 33 342 as a function of time and concentration by flow cytometry and fluorescent microscope. Effects of Hoechst on cell cycle populations were determined by flow cytometry. Enhanced green fluorescent protein (EGFP) expression plasmids with or without AAV inverted terminal repeats (ITR) were constructed and gene expression by transient transfection was compared in the presence of Hoechst. RESULTS: We found that Hoechst 33 258 and 33 342 increase both the level and the population of EGFP gene expressing cells, transduced by several different serotypes of rAAV-EGFP. The augmentation of rAAV-EGFP expression occurs in different cell types in a concentration-dependent manner. In addition, the Hoechst 33 258 or 33 342 mediated enhancement of rAAV gene expression correlated with an increase of cells in S phase and G2/M phases of the cell cycle. Finally, gene expression from transfected ITR-containing plasmid DNA was also enhanced by Hoechst dyes. CONCLUSIONS: Our results revealed that two different, although related, DNA-binding drugs, Hoechst 33 258 and 33 342, accelerate the kinetics of rAAV transgene expression. These findings may provide the basis for more sensitive assessment of rAAV biological activity and also extend the applications of rAAV for in vivo gene transfer.

Animals↗
PubMed1981

Long-term survivors of acute lymphoblastic leukemia--risk of relapse after cessation of therapy.

The results of cessation of therapy (COT) in 64 long-term survivors (disease-free survival of five years or more) of acute lymphoblastic leukemia (ALL) were analyzed to determine the incidence of relapse off therapy. Thirty-seven of the patients had intermittent central nervous system (CNS) prophylaxis. Total follow-up from diagnosis varied from 5.75 to 27.75 years. The median time off therapy was three years (range, 8 months to 26 years). Eighty-six percent (55/64) of the patients continue in their initial remission. Eight patients had relapse, and one patient had a morphologically different leukemia at recurrence. All the relapses occurred between five to eight years from diagnosis and the cumulative rate of relapse for the period was 0.14. There was no significant difference in the rate of relapse for those receiving CNS prophylaxis (0.08) versus those not receiving CNS prophylaxis (0.19). The difference in the relapse rates for boys (0.24) versus girls (0.04) was statistically significant (P = 0.04). Isolated testicular relapse (ITR) was not seen in any of the 34 boys. The present study confirms the earlier observations by others that relapse is uncommon in ALL patients remaining in remission longer than seven to eight years. ALL patients treated with intermittent CNS prophylaxis administered throughout the period of maintenance chemotherapy appear to be at no greater risk for relapse off therapy than those treated with high-dose initial cranial irradiation and intrathecal methotrexate. The longer duration of therapy and the use of a repetitive reinduction regimen for maintenance seem to be associated with a decreased risk of ITR after discontinuation of therapy for boys and men. There appears to be a small but definite risk of "second" leukemia in the long-term survivors of leukemia.

Antineoplastic Agents↗
PubMed1999

Molecular Weight Effect on Latex Film Formation from Polystyrene Particles: A Photon Transmission Study.

The photon transmission method was used to probe the time evolution of film formation from latex particles. Two different latex films were prepared from high molecular weight (HM) and low molecular weight (LM) polystyrene particles at room temperature and were annealed at various temperatures in 2.5-min time intervals above the glass transition. The increase in the transmitted photon intensity (Itr) is attributed to the increase in "crossing density" at the junction surface. The Prager-Tirrell model was employed to interpret the increase in crossing density at the junction surface. The back and forth activation energies were measured for HM and LM films and found to be around 59 and 87 kcal/mol for a reptating polymer chain across the junction surface. Monte Carlo simulations were performed for photon transmission through a rectangular lattice. The number of transmitted photons (Ntr) was calculated as a function of the mean free path of photons. It was observed that Ntr, similar to Itr, increases as the square of the mean free path of photons is increased. Copyright 1999 Academic Press.

Journal Article↗
PubMed1994

Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975.

We analyzed the 186,102 base pairs (bp) that constitute the entire DNA genome of a highly virulent variola virus isolated from Bangladesh in 1975. The linear, double-stranded molecule has relatively small (725 bp) inverted terminal repeat (ITR) sequences containing three 69-bp direct repeat elements, a 54-bp partial repeat element, and a 105-base telomeric end-loop that can be maximally base-paired to contain 17 mismatches. Proximal to the right-end ITR sequences are another seven 69-bp elements and a 53- and a 27-bp partial element. Sequence analysis showed 187 closely spaced open reading frames specifying putative major proteins containing > or = 65 amino acids. Most of the virus proteins correspond to proteins in current databases, including 150 proteins that have > 90% identity to major gene products encoded by vaccinia virus, the smallpox vaccine. Variola virus has a group of proteins that are truncated compared with vaccinia virus counterparts and a smaller group of proteins that are elongated. The terminal regions encode several novel proteins and variants of other poxvirus proteins that potentially augment variola virus transmissibility and virulence for its only natural host, humans.

Animals↗
PubMed1994

Nucleotide sequence of the telomeric region of the African swine fever virus genome.

The 4-kb terminal BclI fragment of African swine fever virus (ASFV) DNA, including the inverted terminal repetition (ITR), was cloned and sequenced. The sequence showed that the 2.1-kb ITR is composed of a 301-nucleotide-long unique sequence immediately adjacent to the terminal hairpin loop, a set of 38 tandem direct repeats of a 34-nucleotide degenerate sequence, another unique intervening sequence with no remarkable features, and a set of 5 tandem repeats of a 27-nucleotide unit unrelated in sequence to the 34-nucleotide repeat unit. Several short repeats were found scattered along the most distal unique sequence. The proximal half of the terminal fragment possesses one complete and one interrupted copy of genes belonging to multigene family 360.

African Swine Fever Virus↗
PubMed2000

Induction of circular episomes during rescue and replication of adeno-associated virus in experimental models of virus latency.

The synthesis of linear duplex replicative structures (monomers, head-to-head, and tail-to-tail dimers) is an important hallmark of the productive phase of the adeno-associated virus (AAV) life cycle. These structures are generated by a strand-displacement replication mechanism and believed to be a reservoir for single-stranded DNA genomes. During the course of studies with recombinant versions of AAV (rAAV), we discovered the assembly of circular duplex provirus derivatives in latently infected cell lines under conditions permissive for replication (i.e., helper virus dependent). These novel structures were cloned by bacterial trapping revealing a markedly homogeneous structure that included a single copy of the rAAV genome joined head-to-tail about the inverted terminal repeats (ITR). Restriction and sequence analysis of the point of circularization revealed a so-called "TRT" domain, consisting of a single ITR hairpin palindrome flanked by 5' and 3' D sequence elements. The circular conformation was additionally characterized by Southern blotting and confirmed by purification on an ethidium bromide-CsCl gradient where the buoyant density was consistent with circular supercoiled DNA. These findings suggest that AAV replication is accompanied by the assembly of circular duplex structures.

Blotting, Southern↗
PubMed2001

The genome sequence of Yaba-like disease virus, a yatapoxvirus.

The genome sequence of Yaba-like disease virus (YLDV), an unclassified member of the yatapoxvirus genus, has been determined. Excluding the terminal hairpin loops, the YLDV genome is 144,575 bp in length and contains inverted terminal repeats (ITRs) of 1883 bp. Within 20 nucleotides of the termini, there is a sequence that is conserved in other poxviruses and is required for the resolution of concatemeric replicative DNA intermediates. The nucleotide composition of the genome is 73% A+T, but the ITRs are only 63% A+T. The genome contains 151 tightly packed open reading frames (ORFs) that either are > or =180 nucleotides in length or are conserved in other poxviruses. ORFs within 23 kb of each end are transcribed toward the termini, whereas ORFs within the central region of the genome are encoded on either DNA strand. In the central region ORFs have a conserved position, orientation, and sequence compared with vaccinia virus ORFs and encode many enzymes, transcription factors, or structural proteins. In contrast, ORFs near the termini are more divergent and in seven cases are without counterparts in other poxviruses. The YLDV genome encodes several predicted immunomodulators; examples include two proteins with similarity to CC chemokine receptors and predicted secreted proteins with similarity to MHC class I antigen, OX-2, interleukin-10/mda-7, poxvirus growth factor, serpins, and a type I interferon-binding protein. Phylogenic analyses indicated that YLDV is very closely related to yaba monkey tumor virus, but outside the yatapoxvirus genus YLDV is more closely related to swinepox virus and leporipoxviruses than to other chordopoxvirus genera.

Adjuvants, Immunologic↗