Defense styles and choice of nursing career among women.
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Career Choice↗
Biomedical subjects
S Verma
Publications and source records attributed to S Verma.
Potential anti-AIDS naphthalenesulfonic acid derivatives. Synthesis and inhibition of HIV-1 induced cytopathogenesis and HIV-1 and HIV-2 reverse transcriptase activities.
Several naphthalenedi- and trisulfonic acids have been synthesized and evaluated for inhibitory potential against cytopathogenesis and purified recombinant human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) reverse transcriptase (RT). The most potent derivative that emerged from the anti-RT study was a small molecule 6 (MW = 840), a dipalmitoylated derivative of 2,7-naphthalenedisulfonic acid. Analog 6 demonstrated 50% inhibitory concentration (IC50) values of 2.42 and 0.86 microM for HIV-1 and HIV-2 RT, respectively. The second most active compound was also a derivative of the same naphthalenedisulfonic acid but contained only one palmitoyl moiety. This compound 9 displayed IC50 values of 4.8 and 3.7 microM for HIV-1 and HIV-2 RT, respectively. Both analogs 6 and 9 are active at noncytotoxic doses, exhibit slightly higher potencies for the RT of HIV-2 over HIV-1, and demonstrate activities superior to the hexasulfonic acid derivative suramin (IC50 values of 9.4 and 15.5 microM for HIV-1 and HIV-2 RT, respectively). In the cytopathogenesis assay, the most active compound is a bis naphthalenedisulfonic acid derivative 17, containing a flexible octamethylene spacer and exhibiting an in vitro therapeutic index of 29.7. Most striking, however, is the influence of the palmitoyl functionality in the naphthalenedisulfonic acid series to confer activity against both HIV-1 and HIV-2 RT.
Enzyme Inhibitors↗
Phase II study of weekly intravenous menogaril in the treatment of recurrent astrocytomas in adults.
Twenty patients with astrocytomas recurrent after surgery +/- radiation were treated on a phase II protocol of the new anthracycline derivative menogaril 115 mg/m2 administered intravenously once per week. Sixteen patients were evaluable for treatment efficacy. No patient achieved a major therapeutic response. Three patients (19%) had stable disease for greater than 8 weeks, including one who showed minor evidence of tumor regression, but less than 50%. Thirteen patients failed. Treatment was well tolerated. One patient developed granulocytopenia, while none developed thrombocytopenia. Four patients required an interruption in their treatment for one to two weeks because of development of granulocytopenia (one patient) or other reasons. Other toxic effects included arm vein phlebitis and skin irritation, skin discoloration of the infused arm, mild to moderate nausea and vomiting, diarrhea, stomatitis, and a fatal central venous catheter infection. Despite the fact that menogaril appeared to have therapeutic activity against recurrent astrocytomas in our phase I studies, we could not document any activity in this phase II study.
Adult↗
In vitro fertilization in the natural cycle.
In vitro fertilization in the natural or spontaneous reproductive cycle was first described by Edwards and his colleagues in 1980 following the birth of their first natural cycle IVF baby 2 years earlier. Many groups attempted to follow their lead but it was almost ten years later that the next publication of success appeared (Foulot et al, 1989). The concept of IVF in the natural cycle is particularly attractive and so in 1987 our group also started evaluating the technique. Initial success in the patients with tubal lesions was not translated to patients with other infertility indications. Unfortunately the technique as initially developed was relatively inefficient with significant procedural losses at each stage. Over the succeeding four years a number of changes have been introduced and the efficiency considerably improved. Although these changes have improved take-home baby rates, overall pregnancy rates per embryo have not altered and are still lower than spontaneous in vivo pregnancy rates. It is likely that in the future, with current developments in culture techniques and greater understanding of gamete biology, this situation will change significantly.
Female↗
Phase II study of oral menogaril as first line chemotherapy for advanced breast cancer: a National Cancer Institute of Canada Clinical Trials Group study.
The National Cancer Institute of Canada (NCIC) Clinical Trials Group conducted a phase II study of weekly oral menogaril as first-line therapy in 51 patients with incurable, metastatic or locally advanced breast cancer. While no prior chemotherapy for metastatic disease was permitted, prior adjuvant chemotherapy was allowed provided that no anthracycline or anthracene had been given. Forty-eight patients were evaluable for response. Two patients (4%) achieved complete remissions, 9 patients (19%) achieved partial remissions, 26 patients (54%) were stable and 11 patients (23%) failed. At the initial menogaril dose of 275 mg/m2 per week, 13 of 14 patients required a dose reduction and/or a treatment delay of one or more weeks. Therefore, the menogaril dose was reduced to 225 mg/m2 per week for the last 37 patients. At that those, 20 of 37 patients developed grade 3 or 4 granulocytopenia and 22 required dosage delays. At the initial starting dose, the average dose intensity actually delivered was 169 mg/m2 per week. At 225 mg/m2 the average dose intensity actually delivered was 197 mg/m2 per week. Toxic effects included mild to moderate nausea and vomiting, diarrhea, hair loss and occasional hyperpigmentation. In summary, menogaril is an anthracycline derivative that has modest activity when administered orally to minimally pretreated patients with breast cancer.
Adenocarcinoma↗
Phase I study of oral menogaril administered daily for 14 consecutive days.
Twenty-eight patients were treated with oral menogaril daily x 14 every 4 weeks. Granulocytopenia was dose-limiting at 50-60 mg/m2 per day. Neutropenic fever occurred in one patient. Thrombocytopenia occurred in 3 of 6 patients treated with menogaril 60 mg/m2/day. Nausea and vomiting and other toxic effects were generally mild. No cardiac toxicity was seen. One partial remission and three minor responses were noted among 11 previously treated patients with carcinoma of the bladder. One minor response was noted among 3 patients with colorectal cancer. The dose recommended for phase II studies is 50 mg/m2 per day for 14 days. Phase II studies are recommended in carcinoma of the bladder. Gastrointestinal toxicity is substantially less on this schedule than with oral menogaril administered on a weekly or q4wk schedule, but thrombocytopenia may be more common.
Administration, Oral↗
Factors related to psychiatric hospitalisation for first contact patients.
In a consecutive series of 178 first contact patients hospitalisation was significantly related to greater distance travelled, low income, acute onset, short duration, past history of illness and history of substance abuse compared to those receiving outpatient disposition. Hospitalised manics and paranoid schizophrenics had higher BPRS scores while hospitalised non-paranoid schizophrenics had lower scores. There was a significant positive correlation between hospitalisation and BPRS items: grandiosity, excitement, elated mood, motor-hyperactivity and distractibility and negative correlation with somatic concern, anxiety, depressive mood and social incompetence. Stepwise multiple regression analysis found the combination of loss of functioning, social incompetence and grandiosity to best predict disposition decision.
Adolescent↗
Stability of an ofloxacin injection in various infusion fluids.
The stability of ofloxacin was evaluated in 10 different infusion fluids under various storage conditions. Solutions of ofloxacin (0.4 mg/mL and 4.0 mg/mL) were prepared in (1) 0.9% sodium chloride injection; (2) 5% dextrose injection; (3) 5% dextrose and 0.9% sodium chloride injection; (4) 5% dextrose and lactated Ringer's injection; (5) 5% sodium bicarbonate injection; (6) Plasma-Lyte 56 and 5% dextrose injection; (7) 5% dextrose, 0.45% sodium chloride, and 0.15% potassium chloride injection; (8) 1/6 M sodium lactate injection; (9) water for injection; and (10) 20% mannitol injection. Each solution was injected into polyvinyl chloride bags and stored at (1) 24 degrees C for 3 days, (2) 5 degrees C for 7 days, (3) 5 degrees C for 14 days, (4) -20 degrees C for 13 weeks and then 5 degrees C for 14 days, or (5) -20 degrees C for 26 weeks and then 5 degrees C, for 14 days. Samples were assayed initially and after storage by high-performance liquid chromatography and examined for visual clarity, pH, turbidity, and particulates. Ofloxacin was stable in all solutions and under all storage conditions. All of the solutions were clear, pH was stable, and particulate-matter counts were acceptable under all storage conditions (except for the 20% mannitol solution, which formed crystals at 5 degrees C and -20 degrees C). An injectable formulation of ofloxacin was stable for at least 3 days at 24 degrees C, 14 days at 5 degrees C, and 26 weeks at -20 degrees C in all tested infusion fluids. Crystals formed in refrigerated or frozen solutions prepared with 20% mannitol injection.
Bicarbonates↗
Distinct spatial and temporal expression patterns of K+ channel mRNAs from different subfamilies.
Different types of K+ channels play important roles in many aspects of excitability. The isolation of cDNA clones from Drosophila, Aplysia, Xenopus, and mammals points to a large multigene family with several distinct members encoding K+ channels with unique electrophysiological and pharmacological properties. Given the pivotal role K+ channels play in the fine tuning of electrical properties of excitable tissues, we studied the spatial and temporal basis of K+ channel diversity. We report the isolation of two putative K+ channels that define two new subfamilies based upon amino acid sequence similarities with other known K+ channels. Northern blot and in situ hybridization studies revealed differences in the spatial and temporal expression patterns for these two new clones along with mRNAs from other K+ channel subfamilies. Two of the K+ channels studied are predominantly expressed in the brain. One of the "brain-specific" K+ channels is first expressed after about 2 weeks of postnatal cerebellar development and remains at levels about 10-fold higher in the cerebellum than in the rest of the brain.
Amino Acid Sequence↗
Heart preservation solution containing polyethyleneglycol: an immunosuppressive effect?
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Adult↗
Superoxide dismutase activity regulation by spermine: a new dimension in spermine biochemistry and sperm development.
Amines are a group of highly important compounds of biological importance; they are known promoters of cell growth, can complex with nucleic acids and can stimulate DNA-primed RNA polymerase activity. Spermine, a polyamine abundantly present in the secretions of the male accessory sex organs, has received no functional attributes till date. This study had been a pioneer attempt to validate the hypothesis of a metalloenzyme activity modulation by spermine and implicit correlations have been drawn.
Animals↗
Superoxide dismutase activation in thyroid and suppression in adrenal. Novel pituitary regulatory routes.
This study reports that administration of TSH in young female mice results in a concomitant augmentation of SOD activity in the thyroid gland. A strong thyroid-adrenal interdependence was also evident in the form of a marked loss of SOD activity in the adrenal gland in response to TSH administration. Very recently SOD/O2.- system had been identified as a potent H2O2 generator which provides substrate for the action of key enzyme in thyroxine and progesterone biosynthesis, viz. the peroxidase. Thus, these results strongly suggest that trophic hormones tonically stimulate hormone biosynthesis by modulating activation/suppression of specific enzymes, which could be the basis of the tuning sequence.
Adrenal Glands↗
Electrophysiological characterization of a new member of the RCK family of rat brain K+ channels.
A novel member of the RCK family of rat brain K+ channels, called RCK2, has been sequenced and expressed in Xenopus oocytes. The K+ currents were voltage-dependent, activated within 20 ms (at 0 mV), did not inactivate in 5 s, and had a single channel conductance in frog Ringers of 8.2 pS. Compared to other members of the RCK family the pharmacological profile of RCK2 was unique in that the channel was resistant to block (IC50 = 3.3 microM) by charybdotoxin [(1988) Proc. Natl. Acad. Sci. USA 85, 3329-3333] but relatively sensitive to 4-aminopyridine (0.3 mM), tetraethylammonium (1.7 mM), alpha-dendrotoxin (25 nM), noxiustoxin (200 nM), and mast cell degranulating peptide (200 nM). Thus, RCK2 is a non-inactivating delayed rectifier K+ channel with interesting pharmacological properties.
Amino Acid Sequence↗
Functionally distinct subsets of human gamma/delta T cells.
To determine if effector subsets exist among human gamma/delta T cells, we examined the cytokine production and cytotoxic activity of gamma/delta T cell clones with different accessory molecule phenotypes, V delta and V gamma gene expression, and J gamma rearrangements. T cell clones bearing gamma/delta T cell receptor produce an array of cytokines like alpha/beta T cell clones. Individual gamma/delta T cell clones produced a characteristic array of cytokines without correlation with V delta or V gamma gene expression. However, when phenotypic subsets were considered, CD4+ gamma/delta clones produced significantly higher levels of interleukin 2 and granulocyte-monocyte colony-stimulating factor compared with CD4-CD8- and CD8+ gamma/delta clones. Similarly, when cytotoxic potential was assessed, CD4+ gamma/delta clones exhibited minimal activity when compared with CD4-CD8- and CD8+ adult peripheral blood gamma/delta clones. We conclude that functionally distinct gamma/delta T cell subsets exist and suggest that these subsets may correlate with expression of the CD4 accessory molecule.
Amino Acid Sequence↗
A phase II study of menogaril in low-grade non-Hodgkin's lymphoma. An NCI Canada Clinical Trials Group study.
The NCI Canada Clinical Trials Group conducted a phase II study of menogaril given intravenously every 4 weeks in low-grade non-Hodgkin's lymphoma. Fifteen of 26 eligible patients had had no prior therapy. Partial responses were seen in 9 patients (35%). Toxicity was moderate including myelosuppression, nausea, phlebitis, alopecia, and lethargy. This drug has only modest activity in this potentially responsive group of patients.
Antineoplastic Agents↗
Bioavailability and pharmacology of oral idarubicin.
A total of 9 patients entered in a phase I trial who received oral idarubicin daily for 3 days took part in pharmacokinetic studies, and bioavailability studies were performed on 13 additional patients receiving single doses of oral idarubicin alternating with i.v. treatment. The data were best fit by a two-compartment model (distribution and elimination compartments for i.v. drug and absorption and single-phase elimination for oral drug). For different idarubicin doses in the phase I and bioavailability studies, the median values for the terminal half-life of idarubicin varied from 5.6 to 11.6 h. High concentrations of the active metabolite idarubicinol were formed. Idarubicinol was eliminated more slowly than was the parent compound, with median half-lives for different dose levels varying from 8 to 32.7 h. Although most pharmacokinetic parameters were similar in plasma and whole blood, peak concentrations and AUCs in whole blood were about 3-4 times those calculated in plasma for idarubicin and about 1.5-2 times those determined in plasma for idarubicinol, indicating fairly extensive uptake into erythrocytes. Oral bioavailability was determined by comparing oral idarubicin to i.v. drug with respect to the combined idarubicin and idarubicinol plasma AUCs, and it varied from 12%-49% (median, 29%). Bioavailability was essentially the same (30%) when whole-blood values were used. Urinary excretion of the drug was less than 5% of the delivered dose by 96 h. Granulocytopenia correlated with plasma idarubicinol "estimated" clearance and steady-state volume of distribution, with whole-blood idarubicinol AUC, area under the moment curve (AuMC), and "estimated" clearance and volume of distribution, and with whole-blood combined idarubicin and idarubicinol AUCs. This suggests that drug contained in erythrocytes plays a major role in toxicity and that idarubicinol may play a larger role in toxicity than does the parent compound.
Administration, Oral↗
The CD45 protein tyrosine phosphatase is required for the completion of the activation program leading to lymphokine production in the Jurkat human T cell line.
Stimulation of the T cell antigen receptor, TCR-CD3, induces tyrosine phosphorylation of specific cellular proteins through activation of a tyrosine kinase. The possible regulatory role of the CD45 protein tyrosine phosphatase in this process was explored by studying the functional properties of cellular variants of the Jurkat T cell line which have been selected to have normal levels of the TCR-CD3 complex, but low or negative expression of CD45. These variants had less than 20% of the normal membrane tyrosine phosphatase activity. Triggering the TCR-CD3 receptor on the CD45 variants with anti-CD3 mAb induced the activation of a tyrosine kinase. Tyrosine phosphorylation of cellular substrates as well as of the CD3 zeta chain was qualitatively comparable to normal cells although the extent of stimulation was lower. No differences were observed between the variants and the normal cells in the duration of the tyrosine phosphorylation signal. The increase in intracellular calcium concentration following receptor stimulation was also less efficient, suggesting that CD45 is necessary for optimal generation of the second messengers of the activation. The CD45 deficient cells secreted highly reduced levels of lymphokines (IL-2, IL-3 or GM-CSF) after activation by anti-CD3 mAb combined with the phorbol ester TPA. This impaired lymphokines production is related to the absence of CD45 since a CD45+ revertant subclone, isolated from one CD45- clone, produced normal levels of cytokines upon activation via CD3, while CD45- subclones were unable to secrete cytokines following activation via CD3. However, upon activation with Ca2+ ionophore and PMA, all CD45- (sub)clones secreted cytokines at levels comparable to those produced by CD45+ cells. These results show that CD45 is required for cytokine production after activation via the TCR-CD3 complex.
Antigens, CD↗
Clonal analysis of differential lymphokine production in peptide and superantigen induced T cell anergy.
A failure of T lymphocytes to produce interleukin 2 (IL-2) on restimulation may, in part, account for the specific unresponsiveness that accompanies incomplete activation. The evidence to support this has been derived predominantly from the investigation of the molecular basis of anergy in murine type 1 T cells. In this study, the effects of different tolerogenic signals delivered by specific peptide or Staphylococcus aureus enterotoxin on the ability of antigen-specific human T cells to produce lymphokines, both in the induction phase and in established antigen-specific non-responsiveness, have been examined. Although T cell proliferation was decreased by supraoptimal concentrations of specific peptide in the presence or absence of antigen presenting cells, IL-2, IL-4, and interferon gamma (IFN-gamma) synthesis were comparable to that of activated T cells. The different tolerogenic signals, all capable of inhibiting phase of unresponsiveness. Restimulation of anergic T cells with an antigenic challenge failed to induce lymphokine production, with the exception of allergen-reactive T cells that secreted IFN-gamma. This latter observation is relevant to the desensitization of specific responsiveness in allergic disease.
Animals↗