Sezary syndrome--a case report.
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Humans↗
Biomedical subjects
J Mukherjee
Publications and source records attributed to J Mukherjee.
Lipoleiomyoma of uterus--an uncommon lesion.
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Adult↗
Multiple primary visceral malignancy--a review with report of two cases.
Multiple primary cancers are being reported with increasing frequency in recent years, the frequency varying from 0.3 to 4.3% in different studies. A combination of primary cancer of larynx and lung is the most common followed by malignant neoplasm involving lip-larynx, skin-larynx, skin-lung, breast-ovary and breast-endometrium. Two interesting cases of rare combinations of primary cancers are being presented. In the first case primary adenocarcinoma of the gall bladder was associated with appendiceal adenocarcinoma. In the second case primary malignant papillary serous cystadenocarcinoma of right ovary and squamous cell carcinoma of cervix uteri were found.
Appendiceal Neoplasms↗
Effect of oral ondansetron on total cholecystokinin plasma levels following CCK-4 panic challenge procedure in healthy men.
OBJECTIVE: To gain insight into whether ondansetron treatment induces changes in total cholecystokinin (CCKT) plasma levels before and after administration of the cholecystokinin tetrapeptide (CCK-4) panic challenge procedure in healthy men. METHODS: Thirty-eight volunteers received a 50-microgram bolus of CCK-4 60 minutes after a single oral dose (acute treatment) and multiple oral doses (chronic treatment) of ondansetron or placebo. RESULTS: Results showed no difference in CCKT plasma levels of CCKT elimination rate constant between the ondansetron and the placebo groups after either acute or chronic treatment. CONCLUSION: Results from this study suggest that total CCK plasma levels are not influenced by either acute or chronic treatment with ondansetron. However, the effect of ondansetron on the different CCK component fractions still needs exploration.
Administration, Oral↗
Evaluation of monoamine oxidase B inhibition by fluoxetine (Prozac): an in vitro and in vivo study.
Inhibition of monoamine oxidase B was investigated both in vitro and in vivo in rats by using the radioligand, N-(6-[18F]fluorohexyl)-N-methylpropargylamine ([18F]FHMP). Binding affinities of five compounds, deprenyl, clorgyline, fluoxetine, norfluoxetine and citalopram were studied. Fluoxetine and norfluoxetine showed affinities of 17 and 13 microM for monoamine oxidase B, respectively. Acute doses of fluoxetine and norfluoxetine (20 mg/kg) also significantly inhibited (10 to 15%) the binding of the radioligand in vivo while citalopram showed lower affinity (140 microM) for monoamine oxidase B and little effect in vivo. The in vivo effects of the various drugs were directly comparable to their in vitro affinities for binding to monoamine oxidase B in the correlation plot of percent control in vivo binding of [18F]FHMP and binding affinity, -logIC50 (R2 = 0.989). These results provide evidence for a potential role of monoamine oxidase B inhibition in the therapeutic effects of Prozac.
Animals↗
Evaluation of d-amphetamine effects on the binding of dopamine D-2 receptor radioligand, 18F-fallypride in nonhuman primates using positron emission tomography.
We have investigated the ability of dopamine to compete with the binding of the high affinity dopamine D2 receptor positron emission tomography (PET) radioligand, 18F-fallypride. In vitro dissociation of 18F-fallypride with dopamine in rat striatal homogenates exhibited a dissociation rate, k(off), of 1.76 x 10(-2) min(-1) while the association rate constant, k(on), was found to be 5.30 x 10(8) M(-1) min(-1). This resulted in a dissociation constant, K(D) of 33 pM for 18F-fallypride. For in vivo studies, we investigated the effects of reserpine and d-amphetamine treatment on 18F-fallypride in an attempt to study competition of endogenous dopamine with the radioligand at the receptor sites in rats and monkeys. PET experiments with 18F-fallypride in two male rhesus monkeys were carried out in a PETT VI scanner. In control experiments, rapid specific uptake of 18F-fallypride in the striata was observed (0.05-0.06% injected dose (ID)/g) while nonspecifically bound tracer cleared from other parts of the brain. Striata/cerebellum ratios for 18F-fallypride were approximately 8 at 80 min postinjection, respectively. The monkeys received various doses (0.25 to 1.50 mg/kg) of d-amphetamine (AMPH) pre- and postinjection of the radioligand. There was a decrease of specifically bound 18F-fallypride as well as evidence of an enhanced clearance of specifically bound 18F-fallypride after administering AMPH in the two monkeys. The dissociation rates, k(off), of 18F-fallypride without AMPH was <10(-4) min(-1) but after 25 min preadministration of AMPH (1 mg/kg), it was 4.1 x 10(-3) min(-1) and after 17, 45 and 90 min postadministration of AMPH (1 mg/kg) it was 3.6 x 10(-3) to 4.0 x 10(-3) min(-1). Lower doses of AMPH (0.25 mg/kg) had a reduced effect on the binding of 18F-fallypride. No effect was seen until about 30 minutes after the injection of AMPH. Studies with various doses indicated that 18F-fallypride has a maximum response at doses of 0.75-1.50 mg/kg, with an approximately 16%/hour reduction in binding. These results indicate that AMPH stimulated release of endogenous dopamine reduces the specific binding of 18F-fallypride.
Animals↗
Image reconstruction for dynamic PET based on low-order approximation and restoration of the sinogram.
Many image-reconstruction methods have been proposed to improve the spatial resolution of positron emission tomography (PET) images and, thus, to produce better quantification. However, these techniques, which are designed for static images, may be inadequate for good reconstruction from dynamic data. We present a simple, but effective, reconstruction approach intended specifically for dynamic studies. First, the level of noise in dynamic PET data is reduced by smoothing along the time axis using a low-order approximation. Next, the denoised sinograms are restored spatially by the method of projections onto convex sets. Finally, images are reconstructed from the restored sinograms by ordinary filtered backprojection. We present experimental results that demonstrate substantial improvements in region-of-interest quantification in actual and simulated dopamine D-2 neuroreceptor-imaging studies of a monkey brain.
Animals↗
Argyrophilic nucleolar organizer regions in atypical adenomatous hyperplasias, prostatic intraepithelial neoplasias and prostatic neoplasms.
Sections from 104 cases of benign, preneoplastic and neoplastic lesions of the prostate were studied for argyrophilic nucleolar organizer regions (AgNORs). The mean NOR counts in normal controls (2.87) and benign prostatic hyperplasia with or without chronic prostatitis (4.90 and 3.84 NORs/nucleus, respectively) were found to be significantly less (p < 0.001) than that in prostatic intraepithelial neoplasia (PIN) and adenocarcinoma of the prostate (5.65 and 5.78 NORs/nucleus, respectively). The mean AgNOR count of a section with atypical adenomatous hyperplasia was significantly lower than that in PIN. No statistically significant difference was observed between AgNOR counts of high-grade PIN and well-differentiated adenocarcinoma (WDAC; 5.67 vs. 5.78 NORs/nucleus, respectively), however the difference between low-grade PIN and WDAC was statistically significant (5.46 vs. 5.78 NORs/nucleus, p < 0.005). The increase in NOR counts occurred concomitantly with the decrease in the degree of differentiation of adenocarcinoma. Thus, NOR was found to be a good adjuvant to the existing diagnostic parameters to pick up more cases at the stage of PIN when prognosis is better.
Adenocarcinoma↗
Melanotic neuroectodermal tumor of infancy.
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Biopsy, Needle↗
18F-desmethoxyfallypride: a fluorine-18 labeled radiotracer with properties similar to carbon-11 raclopride for PET imaging studies of dopamine D2 receptors.
We have developed (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-18F-fluoropropyl)-2- methoxybenzamide (18F-desmethoxyfallypride) as a fluorine-18 radiotracer with properties analogous to that of 11C-raclopride. In vitro experiments in rat brain homogenates showed an association rate constant of 2.16 x 10(8) M(-1)min(-1) and a dissociation rate constant of 0.073 min(-1). High striatal uptake (up to 0.08% injected dose/cc) of 18F-desmethoxyfallypride in rhesus monkeys was observed in PET experiments. The radiotracer cleared from the striata with a dissociation rate of 1.80 x 10(-2) min(-1). Striatum to cerebellum ratios peaked at 3.0 in 30 min after which they decreased steadily. Intravenously administered haloperidol displaced specifically bound 18F-desmethoxyfallypride with a koff of 0.058 min(-1). Synaptic dopamine released by the treatment of the monkeys with d-amphetamine increased the dissociation rate of 18F-desmethoxyfallypride to 0.83 min(-1) thus reducing specifically bound 18F-desmethoxyfallypride by 56% over a period of 42 mins compared to a reduction of only 20% in controls during this time period. The sensitivity of 18F-desmethoxyfallypride towards competition with dopamine should make this radiotracer useful in PET studies to evaluate in vivo pharmacological effects of various agents that alter levels of endogenous dopamine.
Animals↗
Synthesis, radiosynthesis, and biological evaluation of fluorinated thienylcyclohexyl piperidine derivatives as potential radiotracers for the NMDA receptor-linked calcium ionophore.
Various thienylcyclohexyl piperidine (TCP) derivatives were synthesized and evaluated as potential candidates for use as radiotracers for the in vivo study of the NMDA receptor ion-channel. Modification of the thienylcyclohexylpiperidine was accomplished by substituting its piperidine ring either with other cycloamine rings or N-alkyl-substituted amines, and these two classes of TCP derivatives were synthesized using two different methods. The compounds exhibited affinities ranging from 65 nM up to micromolar in competition assays for the receptor ion-channel labeled with 3H-(+)-MK-801 in rat brain homogenates. Radiosynthesis of 1-[1-(2-thienyl)-4-([18F]fluoro)-cyclohexyl]-1,2,5, 6-tetrahydropyridine was carried out by nucleophilic substitution reaction of 1-[1-(2-thienyl)-4-tosyloxycyclohexyl]-1,2,5,6-tetrahydropyridine with no carrier added 18F-, and the yield was approximately 5-10% (decay corrected) in specific activities of 500-1000 Ci/mmol after reverse-phase HPLC purification. The tracer showed good uptake in rat brains after i.v. injection (approx. 0.10% injected dose/g at 30 min. p.i.). However, the specific uptake in receptor-rich regions (striata, hippocampus, frontal cortex, and parietal cortex) improved only marginally with time compared to cerebellum. Three hours postinjection, parietal cortex showed a maximum ratio of 1.9. Preliminary PET experiment with this radiotracer in a rhesus monkey showed good uptake in the brain regions. However, little retention of the radiotracer was observed in the receptor-rich regions.
Animals↗
Fluorinated benzazepines: 1. Synthesis, radiosynthesis and biological evaluation of a series of substituted benzazepines as potential radiotracers for positron emission tomographic studies of dopamine D-1 receptors.
We have prepared N-alkyl, aryl, fluoroalkyl, fluoroaryl and iodoaryl derivatives of 7-chloro-8-hydroxy-3-methyl-1-(3'-aminophenyl)-2,3,4,5-tetrahydro-1 H-3-benzazepine (SCH 38548) as high-affinity ligands for the dopamine D1 receptor. Binding affinities of the compounds for dopamine D1, D2, and serotonin 5-HT2 receptor sites in rat brain homogenates were measured. The affinity of SCH 38548 for dopamine D1 receptors was found to be 0.53 +/- 0.46 nM, whereas lower affinities (in the micromolar range) for dopamine D2 and serotonin 5-HT2 receptors were found. Alkylation (ethyl, n-propyl and benzyl) and acylation (benzoyl) of the amino group of SCH 38548 did not decrease affinities for the D1 receptors significantly. The fluoroethyl, fluoropropyl, and fluorobenzyl derivatives showed approximately an 8-fold, 9-fold, and 3-fold decrease in affinity for the D1 sites compared to SCH 38548. The N-4-fluorobenzoyl derivative, however, showed a similar affinity for the D1 sites as for SCH 38548. All four fluorinated derivatives exhibited weak binding at D2 and serotonin 5-HT2 receptors. The N-(4-18F-fluorobenzoyl)SCH 38548 was prepared by reacting SCH 38548 with 4-18F-fluorobenzoyl fluoride in 2-5% radiochemical yield with a specific radioactivity of approximately 600-700 Ci/mmol. The N-(3-18F-fluoropropyl)SCH 38548 was prepared by reacting SCH 38548 with 18F-fluoropropyl iodide in 2-5% radiochemical yield with a specific radioactivity of approximately 600-700 Ci/mmol. N-(4-18F-fluorobenzoyl)SCH 38548 failed to localize in the dopaminergic sites in the rat and rhesus monkey brain. Biodistribution of N-(3-18F-fluoropropyl)SCH 38548 in rats showed specific uptake and retention (0.64% injected dose/g at 30 min) of the radiotracer in the striata, with striata-to-cerebellum ratios reaching 12 at 2 h postinjection (p.i.). Positron emission tomography scans in rheusus monkeys indicate selective uptake of the radiotracer in the striata. After IV injection of N-(3-18F-fluoropropyl)SCH 38548, a rapid brain uptake of the tracer from blood was observed. Initial uptake in the striata and cerebellum was approximately 0.02% of injected dose/cc. Nonspecific uptake from the tissue surrounding the striata cleared slowly. The striata-to-cerebellum ratio increased from 1.20 to 3.5 min postinjection to approximately 2.5 at 120 min p.i. The specific uptake of N-(3-18F-fluoropropyl)SCH 38548 in the striata was displaced by IV administration of SCH 24518 (2 mg/kg).
Animals↗
Combination of 5-flucytosine and capsule-binding monoclonal antibody in the treatment of murine Cryptococcus neoformans infections and in vitro.
The efficacy of combination therapy with 5-flucytosine and an IgG1 monoclonal antibody to Cryptococcus neoformans capsular glucuronoxylomannan was studied in vitro with J774. 16 murine macrophage-like cells and in vivo in murine cryptococcal infection. The combination of 5-flucytosine and IgG1 was more effective in reducing the numbers of C. neoformans colony-forming units in vitro and in vivo than either agent alone.
Animals↗
Monoclonal antibody mediated capsular reactions (Quellung) in Cryptococcus neoformans.
Capsular reactions ('Quellung') visible by light microscopy were observed when capsule-binding monoclonal antibody (mAb) was added to Cryptococcus neoformans yeast cells. Capsular reactions were observed with capsule-binding IgM, IgG1, IgG2a, IgG2b, IgG3 and IgA mAbs. Scanning electron microscopy revealed that mAb binding produced a structural change in the fibrillar network of the capsule. The occurrence of capsular reactions with mAbs indicate that this phenomenon can be produced by the binding of antibody to a single epitope.
Animals↗
Protective and nonprotective monoclonal antibodies to Cryptococcus neoformans originating from one B cell.
Two immunoglobulin M monoclonal antibodies (mAbs) derived from the same B cell recognize different epitopes on the capsular polysaccharide of the pathogenic yeast, Cryptococcus neoformans. Their respective epitopes are located in spatially distinct regions of the capsule. Passive administration of one mAb prolonged survival whereas the other mAb did not. The results indicate that specificity is an important determinant of antibody efficacy against C. neoformans and that somatic mutations occurring during the antibody response can affect the protective efficacy of antibodies to C. neoformans.
Amino Acid Sequence↗
Fluorinated benzamide neuroleptics--III. Development of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide as an improved dopamine D-2 receptor tracer.
We have prepared five new analogs (n-propyl, iso-propyl, allyl, n-butyl, and iso-butyl) of the dopamine D-2 receptor antagonist, FPMB which result from modifications of the ethyl group at the pyrrolidine nitrogen in FPMB. As expected, all new derivatives showed higher apparent lipophilicity (log kw), with iso-butyl being the most lipophilic (log kw = 2.52), followed by the allyl derivative (log kw = 2.43). The allyl group showed the largest increase in affinity (from 0.26 nM for the ethyl substituent to 0.03 nM for the allyl substituent, almost 10-fold), followed by the n-propyl substituent which showed approximately five-fold better affinity than did the ethyl substituent. Radiosynthesis of (S)-N-[(1-allyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2, 3-dimethoxybenzamide ([18F]fallypride) was carried out by nucleophilic substitution reaction of (S)-N-[(1-allyl-2-pyrrolidinyl) methyl]-5-(3-tosyloxypropyl)-2,3-dimethoxybenzamide with no carrier added 18F-. [18F]Fallypride was obtained in approximately 20-40% yields (EOS/EOB, decay corrected) in specific activities of 900-1700 Ci/mmol after reverse phase HPLC purification in 60 min from EOB. High striatal uptake (upto 2.5% injected dose/g) of [18F]fallypride in rats was observed with striatal/cerebellar ratios of 17, 42, 63 and 122 at 30, 60, 90 and 120 min post-injection, respectively. PET experiments with [18F]fallypride in a cebus monkey showed a brain uptake of 0.10% injected dose/cc. In rhesus monkeys [18F]fallypride showed rapid specific uptake in the striata (0.04-0.06% injected dose/cc) with striata/cerebellum ratios of approx. 3.0 at 14 min, 5.0 at 35 min and 8 at 70 min post-injection. Specifically bound [18F]fallypride was displaced with haloperidol (1 mg/kg) with a half-life of 18 min in the rhesus monkey.
Animals↗
Monoclonal antibodies to Cryptococcus neoformans glucuronoxylomannan enhance fluconazole efficacy.
Monoclonal antibody (MAb) 2H1, which binds to the capsular glucuronoxylomannan (GXM) of the fungus Cryptococcus neoformans, prolonged survival and decreased fungal burden in an experimental murine infection. Fluconazole (FLU) is a triazole antibiotic which is effective against C. neoformans. The efficacy of MAb 2H1 in combination with FLU was studied in vitro with the murine macrophage-like cell line J7741.16 and in vivo in mice infected intravenously. In vitro, the combination of MAb 2H1 and FLU was more effective than either agent alone in reducing the number of CFU of C. neoformans cocultured with J774.16 cells. In combination with FLU, GXM-binding MAbs of the immunoglobulin M (IgM), IgG1, IgG2a, IgG2b, IgG3, and IgA isotypes were effective in reducing the numbers of CFU in C. neoformans-J774.16 cocultures. For the in vivo experiments, A/JCr mice were infected intravenously with 5 x 10(5) organisms treated with MAb and FLU. The therapeutic effect of MAb 2H1 was primarily to reduce the number of CFU in the lung and the serum GXM level, whereas FLU was most effective in reducing the number of CFU in the brain. Mice receiving combination therapy had lower numbers of CFU in the lung and serum GXM levels than mice treated with FLU alone. Administration of MAb 2H1 with or without FLU had little or no effect on the number of CFU in the brain. The results provide support for combined therapy.
Animals↗
Variable efficacy of passive antibody administration against diverse Cryptococcus neoformans strains.
The efficacy of monoclonal antibody (MAb 2H1) against diverse strains of Cryptococcus neoformans was studied in a murine model of intravenous infection. For six of eight strains, administration of MAb prior to infection prolonged survival of mice. For two strains, 371 and SB4A, administration of MAb prior to infection did not prolong survival in multiple experiments with inocula ranging from 10(2) to 10(6) yeast cells per mouse. Mice infected with strains 371 and SB4A had fewer CFU than non-MAb-treated controls, but the CFU reduction was not sufficient to affect survival. Serum glucuronoxylomannan (GXM) levels varied for the different C. neoformans strains. For mice that did not receive MAb 2H1, there was a positive correlation between lung fungal burden and serum GXM levels. MAb 2H1-treated mice had significantly reduced serum GXM levels. The results indicate that the efficacy of MAb 2H1 administration in prolonging survival and/or reducing organ CFU varies with the C. neoformans strain.
Animals↗