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Biomedical subjects

J Mukherjee

Publications and source records attributed to J Mukherjee.

At least 91 records · Page 5Linked to original sources
PubMed1992

A kinetic study of factor I-mediated modification and release of RBC-bound DNA-anti-DNA immune complexes.

A tritiated DNA-anti-DNA complement--containing immune complex probe was used to define the mechanism of factor I-mediated modification and release of erythrocyte CR1-bound immune complex in 10 normal control subjects. Experiments were performed with preformed immune complex, autologous erythrocytes, and autologous serum. Control experiments were performed by using a single donor source of erythrocytes and commercial factor I. The data demonstrate that the modification-release rate was first order with respect to factor I concentration, the mean half-life of red blood cell-bound immune complex was 1.7 +/- 0.7 minutes, and the mean percent of total immune complex present as unbound complexes was 19 +/- 11. These data are consistent with a clearance model in which factor I-mediated modification and release of red blood cell-bound immune complex plays a significant role in immune complex handling.

Antibodies, Antinuclear↗
PubMed1991

Fluorinated benzamide neuroleptics--2. Synthesis and radiosynthesis of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-3- substituted-2-methoxybenzamides.

Synthesis of a fluorinated benzamide neuroleptic, (S)-N-[(1-ethyl-2- pyrrolidinyl)methyl]-5-(3-fluoropropyl)-2,3- dimethoxybenzamide starting from 3-(3,4-dimethoxyphenyl)-1-propanol in 20-25% overall yield is reported. Radiosynthesis of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]- 5-(3[18F]fluoropropyl)-2-methoxybenzamide([18F]FPHB) and (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3[18F]fluoropropyl)-2,3- dimethoxybenzamide([18F]FPHB) was carried out by nucleophilic substitution reaction of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl-5-(3-tosyloxypropyl)-2-me tho xybenzamide and (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3-tosyloxypropyl)-2,3- dimethoxybenzamide respectively, with no carrier added [18F]fluoride. Both, [18F]FPHB and [18F]FPHB were obtained in approx. 20-30% yields (EOS/EOB, decay corrected). Specific activities of 900-1700 Ci/mmol for [18F]FPHB and 800-1400 Ci/mmol for [18F]FPMB were obtained by reverse phase HPLC purification. Total synthesis and purification time required for either [18F]FPHB or [18F]FPMB was 120 min from EOB.

Antipsychotic Agents↗
PubMed1991

Once- vs. twice-daily nitrendipine in the treatment of mild to moderate hypertension, Canadian Nitrendipine Study Group.

Improved measurement of the plasma concentration of nitrendipine demonstrated a plasma half-life of 17-21 h, allowing once-daily (o.d.) instead of currently twice-daily (b.i.d.) dosing. To determine the effectiveness of nitrendipine given o.d. vs. b.i.d., 78 hypertensive patients, [supine diastolic blood pressure (DBP) of 95-114 mm Hg] were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 10 mg b.i.d. (n = 39) or nitrendipine 20 mg o.d. (n = 39) after a 2-week placebo baseline period. Blood pressures (BPs) were measured in the morning at the end of the dosing interval. Mean +/- SD reduction in supine systolic BP (SBP) and DBP in patients evaluable for efficacy (greater than or equal to 14 days treatment) were 7.2 +/- 16.5 and 7.7 +/- 10.3 mm Hg, respectively, after nitrendipine b.i.d. (n = 38) and 9.4 +/- 15.1 and 9.5 +/- 7.0 mm Hg, respectively, after nitrendipine o.d. (n = 36). Similar falls in BP were found for both regimens in patients completing the full 12 weeks of treatment period (n: o.d. = 28, b.i.d. = 32). Discontinuation due to adverse experiences (AEs) occurred in three patients on b.i.d. and eight patients on o.d., the latter mostly in the first 2 weeks of therapy. Overall, AEs were higher in the o.d. group (% AEs at least possibly related to study medication: o.d. = 44%, b.i.d. = 33%). Most frequent AEs were headache and flushing.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

Efficacy of once daily nitrendipine in mild hypertension: comparison with placebo.

A randomized, double-blind, parallel group study was carried out to compare the antihypertensive efficacy of nitrendipine with that of placebo in 80 mild hypertensives. The dose of nitrendipine was initially 10 mg once daily and was doubled to 20 mg once daily after four weeks in patients who responded poorly (33% of patients on nitrendipine and 49% of patients on placebo required doubling of dose). Blood pressure was assessed 20 to 24 h after dosing. Mean (+/- standard error) reductions in supine systolic and diastolic blood pressures for patients who completed 10 weeks of therapy were significantly greater for the nitrendipine group than for the placebo group (systolic blood pressure 18.1 +/- 2.7 mmHg versus 4.2 +/- 2.5, P less than 0.0001; and diastolic blood pressure 10.6 +/- 1.1 mmHg versus 6.6 +/- 1.3, P = 0.002). A comparison of mean reductions in standing systolic and diastolic blood pressures produced similar results. Goal of therapy (diastolic blood pressure no more than 90 mmHg or reduction of at least 10 mmHg) was achieved in 71% of nitrendipine-treated and 45% of placebo-treated patients (P less than 0.05). Nine of 80 patients randomized to therapy dropped out during treatment (nitrendipine: four adverse experiences and one moved from the area; placebo: two adverse experiences, and drug ineffective in two). Overall, the incidence of adverse experiences considered by the physician to be related to treatment was higher in the placebo group (32%) than in the nitrendipine group (23%). Only flushing had a higher incidence in the nitrendipine group; however, the overall incidence was low (9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure↗
PubMed1991

Effectiveness and tolerability of once versus twice daily nitrendipine in the treatment of mild to moderate hypertension. The Canadian Nitrendipine Study Group.

Improved measurement of plasma concentrations of nitrendipine demonstrates a plasma half-life of 17 to 21 h allowing once daily dosing for antihypertensive treatment. To determine the effectiveness and tolerability of nitrendipine given once versus twice daily, 78 patients with mild to moderate essential hypertension were randomized in a double-blind fashion to 12 weeks of treatment with either nitrendipine 20 mg once daily (n = 39) or nitrendipine 10 mg bid (n = 39). Blood pressures measured at the end of the dosing interval were similar on 20 mg once daily and 10 mg bid. Adverse events considered to be drug related (flushing and headaches) occurred mostly at the beginning of active treatment and more frequently on the once daily dosing, resulting in a greater number of patients being withdrawn from the once daily treatment group. Thus, nitrendipine 20 mg once daily lowered blood pressure as effectively as 10 mg bid but was associated with a higher incidence of adverse events. These could be minimized by starting at nitrendipine 10 mg once daily and increasing to 20 mg once daily after two to four weeks.

Blood Pressure↗
PubMed1990

Synthesis of radiofluorinated analogs of m-tyrosine as potential L-dopa tracers via direct reaction with acetylhypofluorite.

The direct electrophilic radiofluorination of m-tyrosine using [18F]acetylhypofluorite was investigated. Results showed that this reaction was both rapid and efficient with recovered decay corrected yield of 71% radiofluorinated m-tyrosines based on starting [18F]acetylhypofluorite. Specific activity of the product obtained in this study was 100-200 mCi/mmol although 1-5 Ci/mmol are easily achievable with our improved production of [18F]AcOF. Three positional isomers were found and identified by 19F-NMR to be 2-, 4-, 6-fluoro-m-tyrosine with a distribution of 36:11:52, respectively. This measured distribution allowed the assignment of the radio-HPLC peaks. Biological studies are currently underway in our laboratory using these fluoro-m-tyrosines to determine which isomer would be most suited for the evaluation of the dopamine system by positron tomography.

Brain↗
PubMed1988

Radiobrominated m-tyrosine analog as potential CNS L-dopa pet tracer.

Radiobrominated 6-bromo-m-tyrosine (6-BMT) was prepared and the time course of its localization in selected cerebral and peripheral organs in the mouse was determined. Since m-tyrosine is known to have L-dopa-like properties in vivo, our goal was to assess the utility of a radiolabeled analog as a tracer for cerebral L-dopa. Our preliminary results showed that substantial amounts of 6-BMT is extracted by the mouse brain and that the regional distribution and time course of the radiotracer is consistent with uptake in regions rich in dopamine neurons. Although a more thorough biochemical characterization of 6-BMT is necessary, this or other positron emitting analogs of m-tyrosine, such as an 18F labelled analog, may be useful PET tracers for the non-invasive study of dopamine turnover in humans.

Animals↗
PubMed1987

Interaction of the unique competitive inhibitor imidazole and related compounds with the active site metal of carbonic anhydrase: linkage between pH effects on the inhibitor binding affinity and pH effects on the visible spectra of inhibitor complexes with the cobalt-substituted enzyme.

Previous studies on the interaction of carbonic anhydrase (CA) with the unique CO2 competitive inhibitor imidazole and related compounds were all interpreted as showing that an ionizable water ligand on the metal of this zinc metalloenzyme is not displaced by inhibitor binding. Internal inconsistencies in the pH dependence of binding and the pH dependence of the visible spectra of complexes with cobalt-substituted enzyme prompted us to reinvestigate this binding. Visible spectroscopy was used to measure the binding of imidazole and 1,2,4-triazole to Co(II)-substituted human CA I and active site carboxymethylated human CA I (CmCA I) and the binding of 1,2,4-triazole to bovine CoIICA II. The limiting visible spectra for these enzyme-inhibitor adducts were also computed and examined for pH dependence. It was shown that the pKa of visible spectral changes can be independently predicted from studies on the pH dependence of binding. After consideration of possible contributions from effects of His-200 ionization in CA I and CmCA I, and His-64 in CA II, the pH effects on binding affinity and spectra were found to be of the correct magnitude to establish linkage between binding and an ionization. It was also shown, however, that pH effects on binding and spectra cannot distinguish whether neutral imidazole binds to both ionization forms of the enzyme (Zn-OH2 and Zn-OH) or whether neutral imidazole and its anion both bind to only the acid form of the enzyme, presumably after displacing the water. These findings have implications to the crystallographic interpretations on the imidazole-enzyme complex and to the catalytic mechanism of CO2 hydration.

Animals↗
PubMed1987

Interaction of amide inhibitors with the active site of carbonic anhydrase: metal-induced deprotonation of the bound amide group is indicated by slow binding kinetics, by visible spectra of complexes with cobalt enzyme, and by pH effects on binding affinity.

Most carbonic anhydrase (CA) inhibitors bind at the active site metal and either are anions or are capable of deprotonation to yield anions. Much less is known about the interaction of CA with inhibitors that have hitherto been considered to bind as neutral species. We report a study of the reversible amide inhibition of Co(II)-substituted CA by iodoacetamide and ethyl carbamate (urethane), as well as the ambivalent oxamate, the monoamide of oxalate. Visible cobalt spectral changes indicate coordination of all these inhibitors to the metal. The pH dependence of the affinity of carbonic anhydrase isozyme I (CA I) for ethyl carbamate and iodoacetamide is formally consistent with their binding either as anionic species to the acid form of the enzyme or as neutral species to the basic form of the enzyme. The former view is in better accord with the spectral data. Most strikingly, reversible binding of iodoacetamide and ethyl carbamate leads to uniquely slow kinetics of ligand association and dissociation that could be followed by simple mixing. The slow association kinetics suggest the involvement of energetically unfavorable deprotonation of the amide group preceding final coordination. The complex pH profile for inhibition of CA I by the ambivalent oxamate is consistent with coordination through the carboxylate group at low pH and through the deprotonated amide group at high pH. The visible spectrum of the complex of Co(II)CA I with oxamate shows a parallel dependence on pH, reflecting this dual coordination mode. Similarly, oxamate dissociation kinetics were biphasic and could be correlated with the pH-dependent spectral changes.(ABSTRACT TRUNCATED AT 250 WORDS)

Binding Sites↗
PubMed1987

Functional status changes following medical or surgical treatment for cerebral ischemia. Results of the extracranial-intracranial bypass study.

To determine the value of extracranial-intracranial arterial anastomosis (EC/IC bypass), we randomly allocated 1377 patients with symptomatic atherosclerosis of the internal carotid or middle cerebral arteries to medical care alone or to EC/IC bypass with continuing medical care. As previously reported, surgery did not reduce--or significantly increase--the risk of stroke. Functional status data collected during the trial provide new information. Six weeks following entry, surgical patients showed greater dysfunction in the following activities: fluency of speech, getting in and out of bed, sitting down and standing up, toileting, cutting food and pouring beverages, and dressing and undressing. At 4.5 months, surgical patients still exhibited greater dysfunction in toileting, with nonsignificant trends in several other activities. From six months onward, there were no significant differences between the groups. Thus, EC/IC bypass results in transient worsening of functional status beyond the immediate perioperative period.

Activities of Daily Living↗
PubMedDate not supplied

Prenatal stress, moderate fetal alcohol, and dopamine system function in rhesus monkeys.

This study examined the striatal dopamine system integrity and associated behavior in 5- to 7-year-old rhesus monkeys born from mothers that experienced stress and/or consumed moderate levels of alcohol during pregnancy. Thirty-one young adult rhesus monkeys were derived from females randomly assigned to one of four groups: (1) control group that consumed isocaloric sucrose solution throughout gestation; (2) stress group that experienced prenatal stress (10-min removal from home cage and exposure to three random loud noise bursts, gestational days 90 through 145); (3) alcohol group that consumed alcohol (0.6 g/kg/day) throughout gestation; or (4) combined alcohol plus stress group that received both treatments. The subjects were assessed for striatal dopamine system function using positron emission tomography (PET), in which the dopamine (DA)-rich striatum was evaluated in separate scans for the trapping of [(18)F]-Fallypride (FAL) and 6-[(18)F]fluoro-m-tyrosine (FMT) to assess dopamine D2 receptor binding potential (BP) and DA synthesis via dopa decarboxylase activity, respectively. Subjects were previously assessed for non-matching-to-sample (NMS) task acquisition, with ratings of behavioral inhibition, stereotypies, and activity made after each NMS testing session. Subjects from prenatal stress conditions (Groups 2 and 4) showed an increase in the ratio of striatal dopamine D2 receptor BP and DA synthesis compared to controls (Group 1). An increase in the radiotracer distribution volume ratios (DVRs), which is used to evaluate the balance between striatal DA synthesis and receptor availability, respectively, was significantly correlated with less behavioral inhibition. The latter supports a hypothesis linking striatal function to behavioral inhibitory control.

Analysis of Variance↗
PubMedDate not supplied

A sequential scanning of the immune efficiency in astrocytoma (Grade I to Grade Iii), meningioma and secondary glioma patients with and without therapeutic scheduling.

PURPOSE: Glioma induces immune suppression. However, data revealing the immune status in glioma patients with sequential therapeutic interventions is missing. Thus, the study aims at evaluating the sequential immune status of glioma bearing patients (Astrocytoma Grade I to Grade III) receiving conventional therapeutic measures. The results were compared with the immune status of metastatic secondary glioma and meningioma patients where there is minimal immune suppression and the effect of therapeutic intervention on the above score. METHODS: Functional immune parameters of peripheral blood lymphocytes were assayed by CD2 receptors enumeration through E-rosetting and lymphocyte cytotoxicity assay and assessing the generation of reactive oxygen species by NBT assay of peripheral blood macrophages in patient groups bearing Astrocytoma (Grade I to Grade III), meningioma and secondary glioma. RESULTS: Patients bearing Astrocytoma (all 3 grades) showed maximum immune suppression as compared to the normal subjects, diseased meningioma controls, and secondary glioma. Therapeutic interventions viz. radiotherapy, surgery and radiotherapy after surgery and chemotherapy could not recover the suppressed activity of the CD2 bearing lymphocytes and that of peripheral blood macrophages. However, therapeutic scheduling could recover the functional activity of the CD8 bearing lymphocytes and the CD56 NK cells from that of tumor bearing patients. CONCLUSION: Astrocytoma and not meningioma is capable of causing immunesuppression. As the tumor progresses from Grade I to Grade III, a linear reduction in the functional efficacy of immunocytes is seen to occur. Radiotherapy, surgery, and chemotherapy also induces an inhibitory effect towards the host immune system. The inhibitory effect of tumor as well as of therapy were mainly directed towards the CD2 bearing lymphocyte population and the peripheral blood macrophage population.

Antineoplastic Agents↗