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Biomedical subjects

V Gopal

Publications and source records attributed to V Gopal.

At least 37 records · Page 2Linked to original sources

Multiparameter assessment of the cell cycle effects of bioactive and cytotoxic agents.

This paper describes the use of the bromodeoxyuridine/propidium iodide method to assess the effects of bioactive and cytotoxic agents on the kinetic characteristics of acute myelogenous leukemia cells. By careful selection of gates, the following parameters can be measured simultaneously using only 50,000 cells: the proportion of cells in S-phase, the distribution of cells within the S-phase compartment, the relative rate of DNA synthesis, the relative distribution of S-phase times, the proportion of S0 cells, and the proportion of cells in G1 and G2/M. This method was used to demonstrate that while retinoic acid, alpha-interferon, and cytosine arabinoside may all "inhibit" DNA synthesis, the actual effects of these agents differ. Retinoic acid appears to arrest cells in G1 without affecting the rate of DNA synthesis, while alpha-interferon and cytosine arabinoside "inhibit" DNA synthesis by reducing the rate of synthesis per se.

Animals↗

Protooncogene expression in subpopulations of cells from leukemia patients.

This report describes a method for preserving the light scatter patterns of cells in which myc and myb expression are being measured. Exposure of cells to 1% paraformaldehyde for 72 h prior to antibody staining for myc and myb proteins preserved the light scatter patterns. Using this method, myc and myb expression was found to be highest in lymphocytes and monocytes and lowest in granulocytes. The measurement of differences in the level of expression of these genes in subpopulations of leukemia cells obtained from individual patients is possible as is assessment of the levels of expression amongst normal and leukemia cells present in the same patient.

Bone Marrow↗

Abnormal regulation of the myc gene in myeloid leukemia.

To study the regulation of expression of the myc protooncogene, cells from normal individuals and patients with acute myelogenous leukemia (AML), and chronic phase and blastic crisis of chronic myeloid leukemia (CML) cells were put in overnight culture in the presence or absence of fetal calf serum. Myc expression in normal marrow cells and chronic phase CML cells fell after culture in vitro. In contrast, myc expression was maintained or increased in a majority of the AML and blastic crisis CML specimens. These data demonstrate that the regulation of myc expression is disordered in many AML and blastic crisis specimens but not in chronic phase CML cells.

Base Sequence↗

The multiple drug resistance gene, MDR1: expression at the protein and RNA levels.

A comparison of three different approaches to detect MDR1 expression in myeloid leukemia cells was undertaken. With respect to the 4 different antibodies studied, a high proportion of false positive reactions were detected. Substantial discordance between MDR1 expression as indicated by Northern blot analysis, PCR, and immunohistochemistry was found. These findings complicate the clinical interpretation of data derived from these methods.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

c-myc and c-myb expression in acute myelogenous leukemia.

Monoclonal antibodies and flow cytometry were used to detect the expression of c-myc and c-myb in the bone marrow (BM) and peripheral blood (PB) cells of patients with acute myelogenous leukemia (AML). The expression of neither gene was correlated with the percent blast cells in the BM or PB nor was there a correlation between c-myc and c-myb expression. A wide range of expression of each gene was found within each FAB type of AML. Patients who had a high proportion of leukemia cells expressing c-myb were less likely to respond to remission induction therapy than patients in whom a low proportion of cells expressed c-myb. This association appears to reflect an inverse relationship between the proportion of cells expressing c-myb and the sensitivity of leukemia cells to the killing effects of chemotherapy in vivo. Treatment outcome was unrelated to c-myc expression.

Bone Marrow↗

Comparison of two methods for concentrating CD34+ cells from patients with acute non-lymphocytic leukemia.

The aim of the present study was to compare two different methods for obtaining CD34+ cells from the peripheral blood or the bone marrow of patients with acute non-lymphocytic leukemia (ANLL). Twenty-two samples, obtained from 19 patients, were density cut (Ficoll-Hypaque 1.077) and, after incubation with My10 antibody, separated by panning or by immunomagnetic beads. Immunomagnetic beads provided a significantly better separation than panning, either in terms of concentration of CD34+ cells (85.5 +/- 11.6% vs. 55.7 +/- 25.0%, p = 0.003) or in terms of depletion of CD34+ cells (3.9 +/- 8.0% vs. 30.9 +/- 26.3%, p = 0.008). This was consistent with the virtually complete depletion of colony forming cells (CFC) in the CD34 negative fraction and the recovery of virtually all the CFC in the positive fraction in the samples separated by immunomagnetic beads. In conclusion, separation by immunomagnetic beads can allow collection of nearly pure CD34+ and CD34- cell populations from patients with ANLL, thereby facilitating the study of the biological characteristics of these cell populations. Moreover the method is less time consuming than panning and is not toxic to the CFC.

Adolescent↗

Effects of an IL-1 receptor antagonist on acute myeloid leukemia cells.

The effect of an interleukin 1 receptor antagonist (IL-1ra) on the proliferation of acute myelogenous leukemia (AML) cells was investigated. The antagonist reduced the spontaneous clonogenicity of these cells as well as the clonogenicity of these cells subsequent to exposure to the antagonist. The effects of the IL-1ra on the clonogenicity of leukemia cells was observed even when the antagonist failed to inhibit DNA synthesis by the leukemia cell population as a whole. The data are consistent with the concept that the administration of IL-1ra subsequent to cytotoxic therapy has the potential of slowing the regrowth of leukemia cells thereby potentiating the effects of chemotherapy.

Bromodeoxyuridine↗

Correlation between the DNA supercoiling and the initiation of transcription by Escherichia coli RNA polymerase in vitro: role of the sequences upstream of the promoter region.

Binding of Escherichia coli RNA polymerase and the abortive initiation of transcription at the A2 promoter of bacteriophage T7, separately cloned in pBR322, was found to be strongly dependent on the degree of supercoiling of the plasmid. Supercoiling does not seem to play any role in the initiation of transcription at the T7A1 promoter under identical conditions. Plasmid containing T7A2 promoter was found to be less amenable to S1 nuclease in comparison to that having T7A1. Sequence comparison reveals a high G/C content upstream to the -35 region of T7A2 which by extra duplex stability probably renders the initiation of transcription more dependent on the state of supercoiling of the template.

Base Sequence↗

Pseudomonas aeruginosa meningitis treated with ceftazidime.

A case of pseudomonas aeruginosa meningitis secondary to chronic otitis media was successfully treated with ceftazidime and gentamicin intravenously. No intrathecal antibiotics were necessary. Treatment of pseudomonas meningitis has been simplified with the advent of third generation cephalosporins.

Aged↗

Inhibition of the first phosphodiester bond formation catalyzed by Escherichia coli RNA polymerase in the presence of bovine seminal plasmin: promoter dependency.

Inhibition of the abortive initiation of transcription catalyzed by E. coli RNA polymerase has been studied here in the presence of bovine seminal plasmin. Seminal plasmin, which is known to be a stronger inhibitor than rifampicin binds at the same site as rifampicin to RNA polymerase. However, unlike rifampicin, seminal plasmin showed the inhibition of the formation of both the first and second phosphodiester bonds. We observed, in vitro, that the degree of inhibition of transcription was different at different promoters. Thus, the percent of inhibition of transcription initiation by seminal plasmin was much less at r-RNA promoters in comparison to that at the early promoters of bacteriophage T7.

Animals↗

Bovine seminalplasmin [corrected] is a DNA unwinding protein.

The duplex DNA unwinding ability of seminalplasmin [corrected] from bovine semen was examined by treatment of plasmid-protein complexes with calf thymus topoisomerase I and resolution of the topoisomer distributions by agarose gel electrophoresis. Binding of seminalplasmin [corrected] results in a moderate degree of unwinding of supercoiled plasmid. The elongation of the RNA chain by E. coli RNA polymerase over promoter containing template is not inhibited by seminalplasmin [corrected]. However, the reinitiation of transcription is blocked in such cases indicating that seminalplasmin [corrected] inhibits transcription by binding to the initiation site of RNA polymerase.

Animals↗

Decline and disappearance of taste response after interruption of the chorda tympani proper nerve of the rat.

The response amplitude in the chorda tympani proper nerve of rats to taste stimulation has been studied at different times after interruption of the nerve in the middle ear. The results show that the reponse in the nerve declined and disappeared completely within 15 h after the nerve was interrupted. As a first sign of deteriorating function a stage of hypersensitivity was observed. Results obtained during applications of local anesthetic or colchicine and section at different distances from the tongue indicate that the decreased response was the result of an interruption of axoplasmic flow from the nerve cell bodies in the geniculate ganglion to the taste buds.

Anesthesia, General↗

Fulminant pneumococcal infections in 'normal' asplenic hosts.

Five asplenic persons with no other detectable underlying disease had over-whelming pneumococcemia. Four of the patients had undergoing splenectomy for trauma, and the fifth had asplenia as an isolated congenital abnormality. Including the cases presented here, there are now at least 26 reported instances of fatal or life-threatening pneumococcal infections in otherwise-normal asplenic patients. Thus, splenectomy per se is associated with an increased risk of over-whelming pneumococcemia. Although the magnitude of the risk is low, mortality associated with these infections is high. Analysis of the clinical data strongly suggests that undiagnosed febrile episodes in asplenic persons should be treated promptly with antibiotics while awaiting culture results. This strategy should be adopted regardless of the age of the patient or his general state of health. The observation that a limited number of pneumococcal serotypes, particularly type XII, appear to predominate in these cases suggests that pneumococcal vaccine might be highly efficacious in preventing overwhelming post-splenectomy pneumococcal infections in otherwise-normal hosts.

Adolescent↗

Failure of vancomycin treatment in Staphylococcus aureus endocarditis. In vivo and in vitro observations.

In a case of staphylococcal endocarditis, we failed to eradicate Staphylococcus aureus from the blood stream with vancomycin hydrochloride therapy. The strain involved was sensitive to vancomycin by disk diffusion studies but showed a wide disparity between minimal inhibitory and minimal bactericidal concentrations. The lack of a bactericidal effect was probably responsible for the failure of treatment. A synergistic effect was demonstrated for the combination of gentamicin sulfate and methicillin sodium, and the patient was ultimately cured with this combination plus vancomycin. Bactericidal tests are important in choosing an antimicrobial agent for treatment of endocarditis.

Adult↗

On the effects of gymnemic acid in the hamster and rat.

The gustatory activity of the chorda tympani proper nerve has been recorded before and after the application of gymnemic acid to the tongue of hamster and rat. Concentrations of pure gymnemic acid ranging from 1 mg/ml to 10 mg/ml have been used. In the hamster gymnemic acid suppressed the response to solutions of sucrose especially, but it also caused, at higher concentrations, a general suppression of the tast response. The depression caused in the response to sucrose was directly related to the strength of the gymnemic acid and inversely to that of the sucrose solution. In the rat a suppression of the response to saccharin was obtained but no suppression of the taste response to sucrose by gymnemic acid was observed.

Action Potentials↗

Depression of taste responses by local or intravascular administration of salicylates in the rat.

The effects of aspirin and sodium salicylate on the taste response in the chorda tympani proper nerve have been studied during stimulation of the taste receptors in rats with salty, sweet, sour and bitter-tasting solutions. Three methods of administering the drugs were used: locally on the tongue, intravenously into one femoral vein and intraarterially close to the branching of the lingual artery. It was observed that salicylates, given in any of these three ways, depressed the response to taste stimuli. This is discussed in relation to present views on the action of salicylates.

Administration, Topical↗